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Archive for April, 2020

Stem Cell Therapy Clinic Still Evaluating Patients But with Precautions During Covid Closures – Press Release – Digital Journal

Thursday, April 16th, 2020

Denver Regenerative Medicine | Stem Cell Therapy, HRT, Testosterone Clinic, which is based in Denver, Colorado, has announced that they continue to evaluate patients but with the necessary precautions during the Covid closures. They realized that there could be people with back pain who cant wait for the quarantine to be over. For those who are looking for pain relief during this time, they can still schedule an appointment for back pain, and the clinic can still offer procedures as they are necessary medical care.

Dr. Joel Cherdack of Denver Regenerative Medicine says, If you feel that your back pain cant wait until the quarantine is over, dont hesitate to contact us. Well be taking all of the necessary precautions to avoid the spread of the virus but well be ready to serve your needs.

He continues, There are many advantages to stem cell therapy at our Denver Regenerative medicine clinic over surgery including faster recovery, less pain, lower cost, decreased or eliminated need to immobilize with a sling or cast and other benefits as well. Before any procedure takes place, we will meet with you for an initial consultation to evaluate your injuries and determine the best stem cell injection options for you.

Stem cells are extracted from the body of the patient and may be used to treat pain through the regeneration of damaged tissue. These cells are self-renewing and can grow into any kind of cell required by the body. Because stem cells from the patient are used to establish a customized treatment plan, there is less risk of the body rejecting the cells and can enhance the bodys own natural rejuvenating abilities.

The stem cell therapy procedure has three basic steps. First, the stem cells are extracted from bone marrow, body fat, or other tissue. Second, the stem cells are conditioned to maximize their healing capability. And third, the stem cells are injected into the area where they can have their maximum effect. Denver Regenerative Medicine utilizes stem cell therapy for the treatment of the deterioration of the joints of the elbows, knees, hips, and shoulders and to enhance the healing of soft tissues. Those who would like to know more about stem cell therapy and the clinic may want to follow the Denver Regenerative Medicine Facebook page.

Meanwhile, hormone replacement therapy (HRT) is offered for hormone imbalance problems. For men, HRT may be able to combat a number of symptoms, such as reduced interest in sex, erectile dysfunction, lower muscle mass and increased body fat, fatigue, loss of body and facial hair, and depression and cognitive issues. For women, HRT may be able to deal with a number of issues, such as thinning hair; irregular menstrual cycles; painful or unusually heavy periods; weight gain; increased growth of hair on the face, chest, neck, or back; hot flashes; and vaginal dryness.

Also available is the REjuvenate Therapy (for Men & Women), which is a combination of stem cell therapy and hormone replacement therapy. The combination results in a synergy between the two treatments to fight the illnesses caused by hormone imbalance, which could be the result of toxins, stress, and other natural factors.

Denver Regenerative Medicine also offers the unique AcCELLerate Stem Cell regeneration system. It combines the patients own stem cells and platelet rich plasma (PRP) for a combination of activated stem cells and platelets. This combination allows all of the growth factors from the PRP to immediately activate the stem cells. Patients who received this combination of stem cells and activated platelets noticed results about 30 percent faster compared to those who only received stem cells. Furthermore, the improvement was sustained over a longer period for the patients who received the AcCELLerate Stem Cell therapy.

Those who are interested in stem cell therapy and the other therapies available at Denver Regenerative Medicine | Stem Cell Therapy, HRT, Testosterone Clinic may want to check out their website at https://denverregenerativemedicine.com/, or contact them on the telephone, or through email. They are open from 10:00 am to 6:00 pm on Mondays, and from 8:00 am to 6:00 pm, from Tuesday to Thursday.

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For more information about Denver Regenerative Medicine | Stem Cell Therapy, HRT, Testosterone Clinic, contact the company here:

Denver Regenerative Medicine | Stem Cell Therapy, HRT, Testosterone ClinicDr. Joel Cherdack(720) 583-1648info@denverregenerativemedicine.comDenver Regenerative Medicine | Stem Cell Therapy, HRT, Testosterone Clinic2149 S Holly St #200Denver, CO 80222

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Stem Cell Therapy Clinic Still Evaluating Patients But with Precautions During Covid Closures - Press Release - Digital Journal

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Vanda Pharmaceuticals Announces Initiation of "CALYPSO" to Study the Role of Genetic Variation in COVID-19 Infections in Collaboration With…

Thursday, April 16th, 2020

WASHINGTON, April 15, 2020 /PRNewswire/ --Vanda Pharmaceuticals, Inc.(Vanda) (Nasdaq: VNDA) today announced the initiation of the CALYPSO program to study the role that human genetic variations play in SARS-CoV-2 ("COVID-19") infection and disease progression. As a part of the CALYPSO program, Vanda will collaborate with University of Washington School of Medicine and its Virology Lab on a pharmacogenetics study in patients with COVID-19. The study will focus on the sequencing of the genome of individual patients, as well as the COVID-19 virus, and the identification of genetic factors that correlate with disease progression and outcomes.

In support of this study, Vanda and UW Medicine plan to collect Whole-Genome Sequencing ("WGS") data from over 1,000 patients with COVID-19 infection, and perform Viral Genome Sequencing, which should enable Vanda and the UW Medicine Virology Lab to explore host susceptibility, associations of WGS with clinical outcomes and severity of disease, as well as host-virus interactions. The study is scheduled to begin enrollment in the coming weeks and will be open to patients in hospitals and clinics around the United States.

"We look forward to the advancement of our program and the opportunity to work with and leverage the expertise of UW Medicine to expand our understanding of the COVID-19 infection mechanism," said Mihael H. Polymeropoulos, M.D., President and Chief Executive Officer of Vanda.

"The study has the potential to provide new insights into virushost interactions that could lead to more effective public health strategies and the design and development of vaccines and therapeutics," said Sandra P. Smieszek, Ph.D., Head of Genetics at Vanda. "With the vast amount of data we expect to collect, the team will aim to discern the factors associated with severity and other critical, clinical characteristics of the infected individuals."

"By leveraging our sequencing expertise and capabilities in collaboration with Vanda, we will be able to provide the necessary insight for potentially life-saving solutions for patients," said Alex Greninger M.D., Ph.D., M.S., M.Phil., Assistant Professor, Laboratory Medicine, Assistant Director, Virology Division at the University of Washington School of Medicine. "We believe this collaboration will help answer critical questions and hopefully outcomes in the fight against COVID-19."

"We are grateful to collaborate with Vanda as we try to find better ways to care for people currently suffering from COVID-19, and as we develop plans for the next phase of the national response," said Keith R. Jerome, M.D., Ph.D., Head of Virology Division at the University of Washington School of Medicine. "The approach of combining host and viral genomics to identify the most promising treatments may serve as a model for future efforts around the world. This unique agreement positions UW Medicine and Vanda for potentially changing the course of the COVID-19 pandemic."

"This is the type of collaboration we need to bring solutions to patients suffering in this time of crisis," said Dr. Greninger. "We look forward to getting this important work underway."

About Vanda Pharmaceuticals Inc.

Vanda is a leading global biopharmaceutical company focused on the development and commercialization of innovative therapies to address high unmet medical needs and improve the lives of patients. For more on Vanda Pharmaceuticals Inc., please visit http://www.vandapharma.com and follow us on Vanda's Twitter and LinkedIn.

About UW Virology

The UW Virology is one of nine divisions comprising the Department of Laboratory Medicine at the University of Washington School of Medicine. The UW Medicine Virology Clinical Laboratories perform diagnostic testing for a full range of human pathogens including respiratory viruses, herpes group viruses, HIV, hepatitis, and enteric viruses, and was one of the earliest providers of COVID-19 testing. The Division provides the highest quality patient care and serves as a model of excellence for clinical laboratories across the nation. Its UW Virology Lab is also recognized as a worldwide leader in virology research. UW Medicine Virology's research programs integrate the latest in computational, laboratory, and clinical research methods to advance the understanding of infectious diseases. Many past and current faculty members in the Virology Division have received prestigious awards recognizing their scientific achievements.

Vanda Contact:

AJ Jones IIChief Corporate Affairs and Communications OfficerVanda Pharmaceuticals Inc.202-734-3400

pr@vandapharma.com

UW Medicine Contact:

Susan GreggDirector, Media Relations206-616-6730

sghanson@uw.edu

CAUTIONARY NOTE REGARDING FORWARD LOOKING STATEMENTS

Various statements in this release are "forward-looking statements" under the securities laws. These forward-looking statements include, without limitation, statements regarding the design, enrollment and anticipated findings of the CALYPSO program, the promotion of more effective public health strategies and the design and development of vaccines and therapeutics. Forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions and uncertainties. Important factors that could cause actual results to differ materially from those reflected in Vanda's forward-looking statements include, among others: Vanda's ability to enroll patients for, and successfully conduct, the study described in this press release; the ability of Vanda, either alone or with its partners, to process the data collected and subsequently develop effective vaccines or therapeutics; the ability to obtain FDA approval of any such vaccines or therapeutics; and other factors that are set forth in the "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of Vanda's annual report on Form 10-K for the fiscal year ended December 31, 2019, which is on file with the SEC and available on the SEC's website at http://www.sec.gov. Additional factors may be set forth in those sections of Vanda's annual report on Form 10-Q for the fiscal quarter ended March 31, 2020, to be filed with the SEC in the second quarter of 2020. In addition to the risks described above and in Vanda's annual report on Form 10-K and quarterly reports on Form 10-Q, other unknown or unpredictable factors also could affect Vanda's results. There can be no assurance that the actual results or developments anticipated by Vanda will be realized or, even if substantially realized, that they will have the expected consequences to, or effects on, Vanda. Therefore, no assurance can be given that the outcomes stated in such forward-looking statements and estimates will be achieved. All written and verbal forward-looking statements attributable to Vanda or any person acting on its behalf are expressly qualified in their entirety by the cautionary statements contained or referred to herein. Vanda cautions investors not to rely too heavily on the forward-looking statements Vanda makes or that are made on its behalf. The information in this release is provided only as of the date of this release, and Vanda undertakes no obligation, and specifically declines any obligation, to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

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SOURCE Vanda Pharmaceuticals Inc.

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Vanda Pharmaceuticals Announces Initiation of "CALYPSO" to Study the Role of Genetic Variation in COVID-19 Infections in Collaboration With...

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Antibody testing: The promise and pitfalls of using them to reopen the US – PolitiFact

Thursday, April 16th, 2020

As Americans yearn for a future with work, shopping and outings with friends, one concept may become a crucial prerequisite: the widespread use of antibody tests.

Antibody tests, also known as serology tests, are designed to detect the presence of antibodies proteins that are key elements of the bodys immune response to germs. Antibodies would be present in people who battled the coronavirus and recovered, as well as in people who had been exposed but whose infection was so mild that they didnt notice they were sick.

If someone has antibodies from exposure to the coronavirus, that person should have immunity to the virus, at least for a period of time. (More on that in a bit.) That means they can go out into the wider community without fear of getting sick themselves. Antibody tests could also be helpful for making staffing decisions in medical units treating coronavirus patients.

Anthony Fauci, a top federal official in the fight against the coronavirus, has floated the idea of "immunity certificates" based on antibody testing. "As we get to the point of considering opening the country, it is very important to understand how much that virus has penetrated society," Fauci said on CNN.

Its also a key element of Democratic presidential candidate Joe Bidens plan for reopening the country. And New York Gov. Andrew Cuomo has gone so far as to develop and start implementing an antibody testing system for New York State. "We cannot restart life as we knew it without testing," Cuomo has tweeted.

PolitiFact interviewed several experts about the promise and potential pitfalls of antibody testing.

What has been done so far?

The Food and Drug Administration has already granted an "emergency use authorization" for one particular antibody test manufactured by a company called Cellex. The FDA also green-lighted other tests for the market without the usual review process, as long as they are labeled with disclaimers that the agency has not fully reviewed them.

That enabled more than 90 tests to go to market, some from academic organizations and some from medical companies, according to Politico. The CDC itself is working to produce one. Researchers at Stanford University have produced one test, while Mount Sinais Icahn School of Medicine has produced another.

The key to developing antibody tests is to have an appropriate coronavirus protein, "because thats what antibodies recognize," said Elizabeth McNally, director of the Center for Genetic Medicine at Northwestern Universitys Feinberg School of Medicine.

The tests work by having some viral protein adhered to a surface, McNally said. "A persons blood sample is mixed with a virus protein and is tested for whether there is an interaction between antibodies in the persons blood and the antibody on the surface."

The good news is that many of the tests are not overly complicated, often requiring blood from a self-administered finger prick. Some have a turnaround time as rapid as 10 to 15 minutes.

How accurate are these antibody tests?

Thats the bad news: The tests so far have not been especially accurate.

In mid April, the FDA said the National Cancer Institute would start reviewing tests for accuracy. This move was welcomed by medical experts.

The United Kingdom has already pulled some tests for inaccuracy. Many antibody tests now being rolled out "may not be as accurate as wed like," FDA commissioner Stephen Hahn has acknowledged. Scott Becker, CEO of the Association of Public Health Laboratories, went so far as to label many of the tests "crappy," CNN reported.

"There is very limited data, almost none peer-reviewed, evaluating how well these tests perform," said Elitza S. Theel, director of the infectious diseases serology laboratory at the Mayo Clinic. "So its critical that laboratories carefully perform validation and verification studies to ensure that the test they are offering for clinical testing is accurate."

A key metric will be a tests "sensitivity," which refers to the percentage of positive tests that reflect genuine infections. "Anything less than 99% would mean too many cases in the population are wrongly identified, throwing off population estimates," said Theo Vos, a professor at the University of Washingtons Institute for Health Metrics and Evaluation.

Will antibodies actually confer immunity?

Scientists expect that a past infection will produce some immunity. But they arent entirely certain of it, and it remains unclear how long that immunity could last.

Generally speaking, the degree and duration of immunity from an infection varies depending on the germ in question. Immunity from common cold viruses last a few weeks; immunity from chickenpox can last decades. Many infectious diseases fall somewhere in between.

One hopeful sign is that an infection with the virus that causes SARS, which is similar to COVID-19, produces an antibody response for a year, maybe more. Thats not as long as some diseases, but it could buy time until a successful vaccine is produced, which experts say could happen within 12 to 18 months.

One unknown is whether that immune response from a past coronavirus infection is strong enough to actually preclude a new infection.

COVID-19 probably gives immunity to "most people, but we dont know for sure that is the case in every recovered COVID patient," said Angela Rasmussen, associate research scientist at the Center for Infection and Immunity at the Columbia University Mailman School of Public Health. "We dont know what levels of antibodies confer protection either, so we should not assume that just having antibodies guarantees that you have completely protective immunity. Theres still a lot more to learn."

What are some of the practical challenges of administering tests?

One practical concern is when to collect samples from individuals.

"We know it takes over a week in some cases to mount an immune response to the virus and to develop a detectable level of antibodies," Theel said. "The samples need to be collected at a certain time after symptom onset. Using samples collected too soon would lead to negative results simply because the patient hasnt developed an immune response to the virus yet."

By the same token, additional testing may be necessary to confirm that someone who is antibody-positive is no longer experiencing an active infection that can get others sick.

Another practical issue is where the test should be administered.

"We dont want to have people rushing to a doctors office or a hospital since that could actually worsen the spread of the virus," McNally said. "Some companies are producing small individual test kits which will produce a + or - result. Some of these tests will require a doctors order and some may become commercially available."

For instance, McNallys institution, Northwestern University, is developing a kit that is designed to be sent through the mail. Once returned via mail with a blood drop on specially treated paper, the tested individual can find out their result a few days later through a secure website.

What can antibody testing tell us about society at large, rather than just the individual?

Knowing how many people are immune will be a key element of the decision to reopen the economy. However, undertaking society-wide testing will require coordinated effort.

Already, some studies are under way. The World Health Organization is working on a study of a half-dozen nations, while one effort in the U.S. is already collecting blood samples in such cities as New York, Seattle and Minneapolis. Other studies are occurring in Michigan, Miami and Los Angeles.

One study completed in a hard-hit town in Germany recently found that 14% of those tested had antibodies to coronavirus.

McNally said research studies like these are important because they "allow us to be able to know how the population has developed immunity. We will want to know what percentage of the population has developed antibodies and how this differs across neighborhoods and areas. This is the type of information that will help to guide decisions about bringing people back to work and future safety issues."

What needs to be done to enable large-scale antibody testing?

Vos recommends focusing on a small number of the most promising tests, then scaling up production. The expected high demand for antibody tests should help push companies to do this quickly, he said. In the meantime, he said, poorly performing tests should be restricted and the FDA should accelerate its regulatory process.

"Things are happening quickly, but without strong oversight there will be a flood of undocumented tests in use, muddying the waters for anyone trying to make sense of what is going on in the community," Vos said.

Its also important to note that antibody tests are just one part of whats needed to restart the economy. Experts say it will also require a system of widely available diagnostic tests to determine if someone has an active coronavirus infection, along with "contact tracing," a method of identifying people who were in close proximity to other people who were infected, so that they can be tested and, if necessary, quarantined.

CDC director Robert R. Redfield told NBC News that large-scale antibody testing could fall into place "over the next several months."

McNally told PolitiFact that she expects antibody testing to be ramping up in May.

"We know most people take about four weeks to develop antibodies and immunity, so assuming exposure to the virus occurred in March or April, we really want testing working at scale in May," she said. "I think were on target for that."

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Axovant Announces Partnership with Invitae to Increase Access to Genetic Testing and Accelerate Diagnoses of GM1 and GM2 Gangliosidosis – Yahoo…

Thursday, April 16th, 2020

NEW YORK and BASEL, Switzerland, April 15, 2020 (GLOBE NEWSWIRE) -- Axovant Gene Therapies Ltd., a clinical-stage company developing innovative gene therapies for neurological diseases, today announced its collaboration with Invitae, a leading medical genetics company, in the Detect Lysosomal Storage Diseases (Detect) program to facilitate faster diagnoses for children with lysosomal storage disorders (LSDs), including GM1 gangliosidosis and GM2 gangliosidosis, also known as Tay-Sachs/Sandhoff disease. Invitae offers genetic testing and counseling at no charge to patients suspected of having an LSD.

Axovant is committed to developing novel gene therapies for those living with rapidly progressive neurodegenerative diseases. We are hopeful that our collaboration with Invitae will provide families with easier access to genetic testing and bring us one step closer to identifying patients who may benefit from potential therapies, said Parag Meswani, PharmD., Axovants SVP of Commercial Strategy & Operations. Our AXO-AAV-GM1 clinical program targeting GM1 gangliosidosis is currently enrolling at the National Institutes of Health, and we are seeking IND clearance for the AXO-AAV-GM2 clinical trial targeting Tay-Sachs and Sandhoff diseases. Early intervention is ideal with potentially disease-modifying genetic therapies, and our diagnostics partnership with Invitae should allow us to identify and enroll children at even earlier stages of disease progression.

LSDs are progressive, multi-system, inherited metabolic diseases associated with premature death, and genetic testing is a crucial first step to arriving at a diagnosis. LSDs are misdiagnosed or undiagnosed in the majority of patients. The Detect program includes a specific LSD testing panel of 53 genes designed to provide patients and families accurate information quickly to preserve valuable treatment time.

Genetic testing can expedite an accurate diagnosis, facilitate earlier interventions, allow genetic counseling of family members, and support clinical research for LSDs such as GM1 and GM2 gangliosidosis, said Robert Nussbaum, M.D., chief medical officer of Invitae. Were pleased Axovant has joined the Detect program to help offer no-charge, sponsored genetic testing for those patients suspected of having the disease.

Research has shown no-charge testing programs with large well-designed panels help increase utilization of genetic testing, which can shorten the time to diagnosis by as much as 2 years in some conditions. Accurate diagnoses enable clinicians to focus on providing disease-specific care sooner, helping reduce costs and improve outcomes.

Additional details, as well as terms and conditions of the program, can be found at https://www.invitae.com/en/detectLSDs/.

About Axovant Gene Therapies

Axovant Gene Therapies is a clinical-stage gene therapy company focused on developing a pipeline of innovative product candidates for debilitating neurodegenerative diseases. Our current pipeline of gene therapy candidates targets GM1 gangliosidosis, GM2 gangliosidosis (including Tay-Sachs disease and Sandhoff disease), and Parkinsons disease. Axovant is focused on accelerating product candidates into and through clinical trials with a team of experts in gene therapy development and through external partnerships with leading gene therapy organizations. For more information, visit http://www.axovant.com.

About Invitae

Invitae Corporation (NVTA) is a leading medical genetics company, whose mission is to bring comprehensive genetic information into mainstream medicine to improve healthcare for billions of people. Invitae's goal is to aggregate the world's genetic tests into a single service with higher quality, faster turnaround time, and lower prices. For more information, visit the company's website atinvitae.com.

Forward-Looking Statements

This press release contains forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as "may," "might," "will," "would," "should," "expect," "believe," "estimate," and other similar expressions are intended to identify forward-looking statements. For example, all statements Axovant makes regarding costs associated with its operating activities are forward-looking. All forward-looking statements are based on estimates and assumptions by Axovants management that, although Axovant believes to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that Axovant expected. Such risks and uncertainties include, among others, the initiation and conduct of preclinical studies and clinical trials; the availability of data from clinical trials; the expectations for regulatory submissions and approvals; the continued development of its gene therapy product candidates and platforms; Axovants scientific approach and general development progress; and the availability or commercial potential of Axovants product candidates. These statements are also subject to a number of material risks and uncertainties that are described in Axovants most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on February 10, 2020, as updated by its subsequent filings with the Securities and Exchange Commission. Any forward-looking statement speaks only as of the date on which it was made. Axovant undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise.

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Media Contact:

Parag MeswaniAxovant Gene Therapies(212) 547-2523investors@axovant.commedia@axovant.com

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‘Smart toilet’ recognizes users and checks for signs of disease – Medical News Today

Thursday, April 16th, 2020

A team at Stanford Medicine has developed gadgets that can be fitted in an ordinary toilet to screen urine and feces and upload the encrypted health data. The technology may be particularly useful for monitoring individuals at high risk of developing particular illnesses.

Many people will be uncomfortable with the idea of cameras and sensors in their toilet. It may seem like an unthinkable intrusion into what is perhaps the most private of all activities.

But a team of developers at Stanford Medicine in Stanford, CA, believe the clinical benefits of their smart toilet could be far-reaching.

They are also confident that their toilet can safeguard the privacy of users.

Technologies that continually monitor a persons health play a growing role in healthcare.

Existing devices include smartwatches for collecting data, such as heart rate, and wearable blood pressure monitors. A skin patch is in development that tracks movement, heart rate, and breathing.

The thing about a smart toilet, though, is that unlike wearables, you cant take it off, says Prof. Sanjiv Gambhir, chair of radiology at Stanford Medicine. Everyone uses the bathroom theres really no avoiding it and that enhances its value as a disease-detecting device.

Prof. Gambhir believes the smart toilet may be particularly useful for monitoring people at high risk of conditions, such as prostate cancer, irritable bowel syndrome (IBS), and kidney failure, due to their genetic predispositions, for example.

His team developed a suite of gadgets that a person can fit in the bowl of an ordinary toilet. Its sort of like buying a bidet add-on that can be mounted right into your existing toilet, he says. And like a bidet, it has little extensions that carry out different purposes.

In a pilot study, 21 volunteers tested the device over several months.

The smart toilet is the perfect way to harness a source of data thats typically ignored and the user doesnt have to do anything differently.

Prof. Sanjiv Gambhir

A motion sensor activates the smart toilet to start capturing video data, which are then digitally analyzed.

One of the smart toilets algorithms can detect abnormal urine flow rate, stream time, and volume, which could be useful for flagging prostate problems in men, for example.

Another gauges the consistency of fecal matter from the images and classifies it according to the Bristol stool chart. This is a standardized system used by clinicians worldwide to diagnose problems such as constipation, gut inflammation, and a lack of dietary fiber.

The smart toilets software can also identify color changes in urine using urinalysis strips (dipstick tests). It can detect 10 different markers, including the number of white blood cells and the levels of specific proteins in the urine. These biomarkers can provide early warnings of diseases, such as kidney infections and bladder cancer.

According to an article describing the technology in Nature Biomedical Engineering, the toilets abilities are comparable to the performance of trained medical personnel.

Encrypted data from the toilet upload to a secure cloud server. In the future, this information could integrate with a healthcare providers record-keeping system for easy access by the individuals doctor.

The Stanford team envisages an app sending a text alert to the healthcare team if the device detects an urgent issue, such as blood in someones urine.

Identifying who is using the toilet will be critical in a household of several people.

The whole point is to provide precise, individualized health feedback, so we needed to make sure the toilet could discern between users, Prof. Gambhir said. To do so, we made a flush lever that reads fingerprints.

However, in case someone uses the toilet and another flushes it, or if the toilet has an auto-flush system, a camera captures what the article calls the distinctive features of their anoderm [skin tissue lining of the anus].

We know it seems weird, but as it turns out, your anal print is unique, says Prof. Gambhir.

The recognition system is fully automatic, which means that no human will see the scans.

Despite the teams best efforts to ensure user privacy and data confidentiality, the smart toilet may prove a hard sell.

A survey conducted by the researchers of 300 prospective users revealed that only 15% described themselves as very comfortable with the concept.

The researchers plans include recruiting more volunteers to test the toilet and individualizing the available tests. A patient with diabetes might want glucose levels in their urine checked, for example.

In addition to urine tests, the team would also like to build into their toilet the ability to carry out molecular analysis of stool samples.

Thats a bit trickier, but were working toward it, says Prof. Gambhir.

If successful, one advantage for the squeamish will be that they no longer have to collect their own stool samples and take them to a clinic for testing.

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'Smart toilet' recognizes users and checks for signs of disease - Medical News Today

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Here’s What We Know about the Most Touted Drugs Tested for COVID-19 – Scientific American

Thursday, April 16th, 2020

As the COVID-19 pandemic continues to claim lives around the world, there are no specific treatments for the disease beyond supportive care. Several drugs already prescribed for other illnesses have shown promise against the novel coronavirus in preclinical studies. And they are now being tested in clinical trials or given to patients on a compassionate-use basis. But experts warn that these medications have yet to prove effective in treating COVID-19 patients.

As of this writing, the virus has infected more than two million people worldwide and caused more than 130,000 deaths. A vaccine and new treatments could take years to fully develop, but the World Health Organization recently launched a large international trial called Solidarity to test four existing therapies. They are the closely related malaria drugs chloroquine and hydroxychloroquine; the antiviral medication remdesivir (originally developed to treat Ebola); the antiviral combination of lopinavir and ritonavir (used for HIV); and those two HIV drugs plus the anti-inflammatory small protein interferon beta. A number of separate clinical trials of these medications and others are underway in several countries, including the U.S.

The U.S. Food and Drug Administration has approved remdesivir for treating COVID-19 patients under the compassionate-use protocol (a designation that gives patients with life-threatening illnesses access to an experimental drug). And the agency has granted an emergency use authorizationwhich allows for otherwise unapproved drugs or uses during an emergencyfor chloroquine and hydroxychloroquine.

None of these therapies are proven, says Stanley Perlman, a professor of microbiology and immunology at the University of Iowa. Only the results of randomized clinical trials can show whether they work, he adds.

Here is what scientists know so far about some of the most prominent drugs currently being tested as treatments for the potentially deadly infection.

President Donald Trump has repeatedly touted the malaria drugs chloroquine and hydroxychloroquine as a treatment for COVID-19despite a lack of clinical evidence that they work for the disease. The presidents comments set off a scramble among doctors and patients to obtain the drugswhich are frequently used to treat autoimmune diseases such as rheumatoid arthritis and lupusand there is now a shortage of them in the U.S. Also, these substances can be dangerous in healthy people: a man in Arizona died after ingesting a fish-tank cleaner containing a type of chloroquine that is not approved for human use. On March 28 the FDA issued an emergency authorization for administering chloroquine or hydroxychloroquine to COVID-19 patientsbut many experts say the widespread usage of these drugs is premature.

The clinical support is very, very minimal, says Maryam Keshtkar-Jahromi, an assistant professor of medicine at the Johns Hopkins University School of Medicine, who co-authored an article in the American Journal of Tropical Medicine and Hygiene calling for more randomized controlled trials of chloroquine and hydroxychloroquine. The drugs do not show strong evidence at this point, she adds.

A few preclinical studies have suggested these compounds could be effective at blocking infection with the novel coronavirus (officially called SARS-CoV-2), but there has been very little good evidence from clinical trials in patients with the illness it causes, COVID-19. A controversial small, nonrandomized trial of hydroxychloroquine combined with the antibiotic azithromycin in France suggested that COVID-19 patients given the treatment had less virus, compared with those who refused the drugs or those at another hospital who did not receive them. But experts have questioned the studys validity, and the society that publishes the journal in which it appeared has issued a statement of concern about the results, according to Retraction Watch. (Scientific American reached out to the papers authors for comment but did not hear back from them.) A preprint study in China also claimed to show that hydroxychloroquine benefitted COVID-19 patients, but it had significant methodology problems, Keshtkar-Jahromi says. The issues included confounding variables, such as the fact that all of the subjects received other antiviral and antibacterial treatments.

Some scientists say the preclinical evidence is strong enough to support chloroquines use, however. We know how it acts at the cellular level against the virus. We have preclinical proof, says Andrea Cortegiani, an intensivist and researcher in the departments of anesthesia and intensive care and of surgical, oncological and oral sciencesat the University of Palermo in Italy. Second, its a cheap drug, available all over world, adds Cortegiani, who is also a clinician at University Hospital Paolo Giaccone in Italy.

Chloroquine and hydroxychloroquine have been hypothesized to work against COVID-19 by changing the pH required for SARS-CoV-2 to replicate. Given their use in autoimmune disorders, these medications could also play a role in dampening the immune response to the viruswhich can be deadly in some patients.

But these drugs cardiac toxicity is a concern, Keshtkar-Jahromi says. There have been some reports of myocarditis, or inflamed heart tissue, in people with COVID-19 who have not taken chloroquine or hydroxychloroquine. If patients receiving one of these medications die of heart complicationsand are not in a clinical trialdoctors cannot know if the drug contributed to higher chance of death.*

A drug that modulates the immune response could also make someone more vulnerable to other viral or bacterial infections. Its a double-edged sword, says Sina Bavari, chief science officer and founder of Edge BioInnovation Consulting in Frederick, Md., who co-authored Keshtkar-Jahromis article in the American Journal of Tropical Medicine. Giving a drug to suppress the immune system has to be done with extreme care.

We are not saying, Dont [prescribe chloroquine], Bavari says. We are saying, More data is needed to better understand how the drug worksif it works.

This experimental antiviral drug was developed to treat Ebola, and it has been shown to be safe for use in humans. It is a broad-spectrum antiviral that blocks replication in several other coronaviruses, according to studies in mice and in cells grown in a lab. In addition to the WHO investigation, at least two trials in China and one in the U.S. are currently evaluating remdesivir in COVID-19 patients. Results for the Chinese trials are expected later this month.

As of this moment, we dont have data for remdesivir in human COVID-19 disease, says Barry Zingman, a professor of medicine at Albert Einstein College of Medicine and clinical director of infectious diseases at Montefiore Health Systems Moses Campus. The two related institutions, both located in New York City, recently joined a nationwide clinical trial of the drug. Our patients are randomized, so we dont know whos getting the drug or a placebo. [But] we have seen some patients do remarkably well, Zingman says. Trial results are on track for publication sometime in the next six to eight weeks, he adds.

As Scientific American reported previously, remdesivir works by inhibiting an enzyme called an RNA-dependent RNA polymerase, which many RNA virusesincluding SARS-CoV-2use to replicate their genetic material. Timothy Sheahan of the University of North Carolina at Chapel Hill and his colleagues have shown the drug is effective against the coronaviruses that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), respectively, as well as some of the viruses behind the common cold. The team is currently in the process of testing the drugs efficacy against SARS-CoV-2. A recent study of compassionate use of remdesivir in 53 severe COVID-19 patients found that 63 percent of those taking the drug improved, but it was not a randomized controlled trial.

Remdesivir has some chance, Perlman says. If we can give [the drug] early in the disease course, it could work. To know for sure, scientists must await the results of the ongoing clinical trials.

One limitation with remdesivir is that it must be given intravenously, so patients can only get it in a hospital. Sheahan and his colleagues at Emory University have recently developed a related drug called EIDD-2801, which can be taken in pill form. Like remdesivir, the medication works as a nucleoside analogue, interfering with viral replication. It was effective at preventing SARS-Cov-2-infected lung cells from replicating in a lab dish and related viruses from doing so in mice.

The HIV drugs ritonavir and lopinavir (sold as a combination therapy by AbbVie under the brand name Kaletra) have been tested against COVID-19 in a few clinical trials. The initial data have not shown them to be effective, however. A study in the New England Journal of Medicine found they conferred no benefit beyond standard care.

The drug combination is what is known as a protease inhibitor, and it works by blocking an enzyme involved in viral replication. But its action is specific to HIV and so is unlikely to work for SARS-CoV-2, Perlman says. If you have the key to a car, and you try to put it in your car, the odds of it working are one in a million, he says. Kaletra [targets] a completely different lock than the one for COVID-19.

Nevertheless, the WHO trial includes a group of COVID-19 patients who will receive these drugs on their ownand another group that will receive them in combination with interferon beta, a small cell-signaling molecule used to treat multiple sclerosis. The molecule is a massive orchestrator of immune response, Perlman notes, so it must be used carefully. In mouse studies of the SARS and MERS coronaviruses, it halted the infections when administered early. When it was given later, he says, the mice died. Using a drug that activates the immune system could be helpful in the beginning of an infection, but giving it too late could be deadly.

Researchers are also considering a number of other therapies that tamp down the rampant immune response seen in severe COVID-19 cases. Such a flood of immune cells in the lungsknown as a cytokine stormcan lead to death. Many of the sickest patients have elevated levels of an inflammatory protein called interleukin-6 (IL-6). Research in China has suggested that Actemra (tocilizumab), an IL-6-blocking antibody drug made by Roche, shows promise against COVID-19. And Chinese authorities have recommended the drug in their treatment guidelines. Roche has since initiated a phase III randomized controlled clinical trial for the medication. In the U.S., Michelle Gongchief of the division of critical care at Montefiore and Albert Einstein and director of critical care research at Montefioreand her colleagues are among dozens of groups conducting a double-blind, placebo-controlled clinical trial of a related drug called sarilumab, which is already approved for treating rheumatoid arthritis. Sarilumab will only be given to the sickest individuals: to be part of the trial, patients must be hospitalized with COVID-19 and in severe or critical condition.

Another treatment approach involves injecting COVID-19 patients with blood plasma from people who have recovered from the illness. The FDA recently issued guidance on the investigational use of such convalescent plasma, which contains antibodies to the coronavirus, and clinical trials are underway.

Blood from disease survivors has been used as a treatment throughout historyfrom polio-infected horses in the 1930s to former Ebola patients in 2014. There is a long-lasting rationale for the use of convalescent plasma against any infectious disease, Cortegiani says. One problem, however, is that scientists do not know whether people develop strong immunity against SARS-CoV-2. And it is not easy to collect plasma containing enough antibodies, he adds. Another issue is the shortage of eligible donors. Some companies are looking into ways to produce these antibodies artificially. In the meantime, a number of hospitals are searching for volunteers to donate plasma.

None of the therapies described above have yet been proved to treat COVID-19. But some answers can be expected in the next few weeks and months as the results of clinical trials emerge. Until then, Cortegiani says, we cannot say, This drug is more promising than the other one. We can only say, There is a rationale for it.

Read more about the coronavirus outbreakhere.

*Editors Note (4/16/20): This paragraph was edited after posting to correct Maryam Keshtkar-Jahromis comments about her concerns with chloroquine and hydroxychloroquine.

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Here's What We Know about the Most Touted Drugs Tested for COVID-19 - Scientific American

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Looking to the Future of Cell and Gene Therapies – Technology Networks

Thursday, April 16th, 2020

At the front lineof advances in personalized medicine are cell and gene therapies. These are two overlapping fields of medical research whereby the overall aim is to treat the underlying causes of both genetic and acquired diseases.

Is the promise of personalized medicine on the edge of being delivered? Decades of research and advances in genomics, cell biology, cancer and analytical technologies have permitted exciting progress in the cell and gene therapy space recently. Technology Networks recently spoke with three of the leaders in this space, Allogene Therapeutics, bluebird bioInc. andMogrify to gain their insights on the next developments in cell and gene therapy.

Joe Foster, COO, Mogrify.

"We are on the cusp of new breakthroughs in this field and that evolution of engineered cell therapy has the potential to expand beyond cancer. Engineering, synthetic biology and gene editing has opened the door beyond allogeneic cell therapy. There is a bright future with transformative technologies that may hold the key to addressing solid tumors."

David Chang, M.D., Ph.D., President, Chief Executive Officer and Co-Founder, Allogene Therapeutics.

"Although gene therapies are still a nascent technology, they present a new paradigm for healthcare, offering a one-time treatment that can address the underlying genetic cause of certain severe genetic diseases and cancer. We anticipate that the three techniques being studied for gene therapy gene editing, gene addition and gene-based immunotherapy will become more distinct and that the entire treatment journey will become more efficient."

Martin Butzal, Head of Medical Europe, bluebird bio.

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Where Did This Coronavirus Originate? Virus Hunters Find Genetic Clues In Bats – NPR

Thursday, April 16th, 2020

Cave nectar bat (Eonycteris spelaea) from Singapore. Justin Ng/Linfa Wang hide caption

Cave nectar bat (Eonycteris spelaea) from Singapore.

Updated at 11 a.m. ET

Dr. Linfa Wang, a virologist at the Duke-National University of Singapore, has been working around the clock to help Singapore fight this coronavirus. He hasn't hugged his daughter in over two months.

"We're in a war zone right now. Everything comes to me very fast," Wang said in an interview with NPR's Short Wave podcast. He's given over 100 interviews since January, when international reports first surfaced of a new coronavirus.

Since then, scientists have learned a great deal about the coronavirus, now called SARS-CoV-2. And one of the mysteries they're still trying to untangle is where the virus came from in the first place. Scientific evidence overwhelmingly points to wildlife, and to bats as the most likely origin.

Wang is an expert in emerging zoonotic diseases, or diseases hosted in animals that spread to humans. The CDC estimates that six out of ten infectious diseases in people come from animals. Among them are Lyme disease, Rabies, West Nile, and diseases caused by coronaviruses, including this coronavirus and the SARS virus.

The 2003 outbreak of SARS was eventually traced to horseshoe bats in a cave in the Yunnan province of China, confirmed by a 2017 paper published in the journal Nature. It was a detective hunt that took over a decade, sampling the feces, urine, or blood of thousands of horseshoe bats across the country and seeing if those samples are a genetic match to the virus.

The work of virus hunting of tracking an outbreak to its origin point can take years. Wang stresses that pinpointing the true origin of this coronavirus will take time as well. "Of course, the technology and everything is much more advanced 17 years later [since the 2003 SARS outbreak]. But, for us to try to solve everything in two to three months is just not feasible."

'This is a product of nature'

In early January 2020, Chinese scientists sequenced the entire genome for SARS-CoV-2 and published it online. Researchers at the Wuhan Institute of Virology in China compared its genome to a library of known viruses and found a 96% match with coronavirus samples taken from horseshoe bats from Yunnan.

"But that 4% difference is actually a pretty wide distance in evolutionary time. It could even be decades," says Dr. Robert F. Garry, professor of microbiology and immunology at Tulane University School of Medicine.

That extra 4% suggests the SARS-CoV-2 may not have evolved from bats alone, but may include viral material from another animal. In that case, the virus would have continued to evolve through natural selection in that animal. Moreover, that other animal may have acted as an "intermediate host," ultimately transmitting the virus to humans.

With this coronavirus, scientists aren't fully clear on whether an intermediate host was involved nor the chain of cross-species transmission to humans. Studies have found a genetic similarity between this coronavirus and coronaviruses found in pangolins, also called scaly anteaters, which are vulnerable to illegal wildlife trade.

Given that some China's earliest COVID-19 patients were connected to the Hunan Seafood Wholesale Market in Wuhan, it is likely the seafood market played a role in amplifying the virus. However, there is not enough evidence to prove that is where the virus transmitted from animals to humans. There is also evidence emerging that among the first 41 patients hospitalized in China, 13 had no connection to this particular marketplace. The path of the pathogen is still unknown.

As for clues the virus holds about its animal origins, Robert Garry and fellow researchers have hypothesized that SARS-CoV-2 could be a blend of viruses from bats and another animal.

"The receptor binding domain actually shares a lot of sequence similarity to a virus that's found in the pangolin" Garry said, referring to the receptor-binding mechanism that allows the virus to form a strong attachment to human cells. "So, those sequences probably did arise from a virus like the pangolin coronavirus, or maybe some other coronavirus that can circulate in pangolins or some other animals." Further genetic analysis is needed to figure this out.

In studying the genome, Garry also confirms the virus came from wildlife. "This is a product of nature. It's not a virus that has arisen in a laboratory by any scientist, purposely manipulating something that has then been released to the public," he said.

'It's A Billion Dollar Question'

So, why are bats such good hosts for viruses?

"I used to say it's a million dollar question. Now I say it's a billion dollar question," said Wang, speaking to NPR's Short Wave podcast on Tuesday.

Bats are critically important for pollinating flowers and dispersing seeds. They catch bugs, the same ones that bite us and eat some of our crops. But bats also harbor some of the toughest known zoonotic diseases.

The Rabies virus, the Marburg virus, the Hendra and Nipah viruses all find a natural reservoir in bats, meaning those viruses live in bats without harming them. The Ebola outbreak in West Africa was traced to a bat colony. The SARS virus originates in bats, along with other coronaviruses. And now, SARS-CoV-2 is linked to bats too.

Wang believes bats' high tolerance for viruses may have to do with the fact that they are the only mammal that's adapted for flight.

"During flight, their body temperature goes all the way to 42 degrees (or 108 degrees Fahrenheit). And their heartbeat goes up to 1000 beats per minute," Wang said.

Flying several hours a day, bats burn a great deal of energy. This creates toxic free radicals that damage their cells, but Wang's research has shown that bats have also evolved abilities to repair and minimize that cellular damage. Those same defensive abilities may help them not only tolerate flight, but also to fight infectious diseases in a way that human bodies cannot.

"Our hypothesis is that bats have evolved a different mechanism to get the balance right for defensive tolerance. And that favors the virus to live peacefully with bats," said Wang.

Peter Daszak, President of the U.S.-based non-profit Ecohealth Alliance, says that even if bats are the origin, they are not to blame for the pandemic.

"It's not bats. It's us. It's what we do to bats that drives this pandemic risk," Daszak said. His research demonstrates how interactions between wildlife and livestock, food and agriculture practices, as well as humans close proximity to animals in densely populated areas, create the conditions for viral outbreaks.

"One of the positive things about finding out that we're actually behind these pandemics is that it gives us the power to do something about it. We don't need to get rid of bats. We don't need to do anything with bats. We've just got to leave them alone. Let them get on, doing the good they do, flitting around at night and we will not catch their viruses," Daszak said.

Given that infectious and zoonotic diseases have been on the rise for decades, Wang is frustrated by the fact that countries around the world failed to understand the impact this novel coronavirus outbreak would have.

"I'm so angry right now. This COVID-19 outbreak, before January 20th, you could say it's China's fault. The Chinese government. But after January 20th, the rest of the world is still not taking it seriously. Our political system, our diplomatic system, our international relationship system is just not ready," Wang said.

January 20th is when Chinese health officials confirmed the new coronavirus could be transmitted between humans and the World Health Organization kicked into high gear to evaluate the global risk. There were more than 200 cases then. Now, the confirmed case count is nearing 2 million worldwide.

Email the show at shortwave@npr.org.

This episode was produced by Brit Hanson, edited by Viet Le, and fact-checked by Emily Vaughn.

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International Pompe Day highlighting those who live with rare genetic condition – KMBC Kansas City

Thursday, April 16th, 2020

Mary Joyce of Overland Park, Kansas, lives each day as if it is a gift because, in her mind, it absolutely is. She lives with the rare Pompe disease, a degenerative muscle disease, which took her sisters life in 2013. My sister passed away only at 53," Joyce said. "I call myself in the bonus years at age 58!April 15 is International Pompe Day. Its a day to highlight the people who live with the genetic condition and to bring attention to it. Joyce said its hard to explain what Pompe has done to her. It looks like youre healthy from the outside, but its all inside," she said. "My muscles are like rubber bands -- like noodles inside. Her sister Shirley was older than her by three years, and was diagnosed first. Joyce said, When she first started having symptoms, and falling inside her house, she would call me and me and the boys would go over and help her. Years after her symptoms started, a doctor in St. Louis diagnosed Shirley. A few years later, Shirley diagnosed her sister. She said, 'You have the waddle!' Joyce said. Shirley noticed the way Marys hips moved when she walked, and urged her to get tested.The test came back positive for Pompe. Both women qualified for a clinical trial for a medication to treat Pompe. Once the double-blind study was completed and a year had passed, the sisters were told Joyce had received the medication. Shirley had not. "I felt so bad that she did not get the drug," Joyce said. "That just broke my heart. I thought why did I get it? I didn't deserve it. She was having symptoms. I was just barely starting."When asked what she misses most about her sister, Joyce answered, Everything.Joyce is now a grandmother of two, and is watching her sisters grandchildren grow. She gets enzyme replacement therapy every-other week. And she dreams, "that no one will have to endure this. That itll be somehow wiped out -- that there will be a medicine to get those newborns right away before any damage is done to the sweet babies, and that they have a wonderful, normal life.

Mary Joyce of Overland Park, Kansas, lives each day as if it is a gift because, in her mind, it absolutely is.

She lives with the rare Pompe disease, a degenerative muscle disease, which took her sisters life in 2013.

My sister passed away only at 53," Joyce said. "I call myself in the bonus years at age 58!

April 15 is International Pompe Day. Its a day to highlight the people who live with the genetic condition and to bring attention to it.

Joyce said its hard to explain what Pompe has done to her.

It looks like youre healthy from the outside, but its all inside," she said. "My muscles are like rubber bands -- like noodles inside.

Her sister Shirley was older than her by three years, and was diagnosed first.

Joyce said, When she first started having symptoms, and falling inside her house, she would call me and me and the boys would go over and help her.

Years after her symptoms started, a doctor in St. Louis diagnosed Shirley. A few years later, Shirley diagnosed her sister.

She said, 'You have the waddle!' Joyce said.

Shirley noticed the way Marys hips moved when she walked, and urged her to get tested.

The test came back positive for Pompe.

Both women qualified for a clinical trial for a medication to treat Pompe. Once the double-blind study was completed and a year had passed, the sisters were told Joyce had received the medication. Shirley had not.

"I felt so bad that she did not get the drug," Joyce said. "That just broke my heart. I thought why did I get it? I didn't deserve it. She was having symptoms. I was just barely starting."

When asked what she misses most about her sister, Joyce answered, Everything.

Joyce is now a grandmother of two, and is watching her sisters grandchildren grow.

She gets enzyme replacement therapy every-other week. And she dreams, "that no one will have to endure this. That itll be somehow wiped out -- that there will be a medicine to get those newborns right away before any damage is done to the sweet babies, and that they have a wonderful, normal life.

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When Damaged, the Adult Brain Repairs Itself by Going Back to the Beginning – UC San Diego Health

Thursday, April 16th, 2020

When adult brain cells are injured, they revert to an embryonic state, according to new findings published in the April 15, 2020 issue of Nature by researchers at University of California San Diego School of Medicine, with colleagues elsewhere. The scientists report that in their newly adopted immature state, the cells become capable of re-growing new connections that, under the right conditions, can help to restore lost function.

Repairing damage to the brain and spinal cord may be medical sciences most daunting challenge. Until relatively recently, it seemed an impossible task. The new study lays out a transcriptional roadmap of regeneration in the adult brain.

A cross-section of a rat brain depicts cells (in blue) expressing normal levels of the Huntingtin gene while cells (in red) have had the gene knocked out. The latter cells, without the Huntingtin gene, displayed less regeneration.

Using the incredible tools of modern neuroscience, molecular genetics, virology and computational power, we were able for the first time to identify how the entire set of genes in an adult brain cell resets itself in order to regenerate. This gives us fundamental insight into how, at a transcriptional level, regeneration happens, said senior author Mark Tuszynski, MD, PhD, professor of neuroscience and director of the Translational Neuroscience Institute at UC San Diego School of Medicine.

Using a mouse model, Tuszynski and colleagues discovered that after injury, mature neurons in adult brains revert back to an embryonic state. Who would have thought, said Tuszynski. Only 20 years ago, we were thinking of the adult brain as static, terminally differentiated, fully established and immutable.

But work by Fred Rusty Gage, PhD, president and a professor at the Salk Institute for Biological Studies and an adjunct professor at UC San Diego, and others found that new brain cells are continually produced in the hippocampus and subventricular zone, replenishing these brain regions throughout life.

Our work further radicalizes this concept, Tuszynski said. The brains ability to repair or replace itself is not limited to just two areas. Instead, when an adult brain cell of the cortex is injured, it reverts (at a transcriptional level) to an embryonic cortical neuron. And in this reverted, far less mature state, it can now regrow axons if it is provided an environment to grow into. In my view, this is the most notable feature of the study and is downright shocking.

To provide an encouraging environment for regrowth, Tuszynski and colleagues investigated how damaged neurons respond after a spinal cord injury. In recent years, researchers have significantly advanced the possibility of using grafted neural stem cells to spur spinal cord injury repairs and restore lost function, essentially by inducing neurons to extend axons through and across an injury site, reconnecting severed nerves.

Last year, for example, a multi-disciplinary team led by Kobi Koffler, PhD, assistant professor of neuroscience, Tuszynski, and Shaochen Chen, PhD, professor of nanoengineering and a faculty member in the Institute of Engineering in Medicine at UC San Diego, described using 3D printed implants to promote nerve cell growth in spinal cord injuries in rats, restoring connections and lost functions.

The latest study produced a second surprise: In promoting neuronal growth and repair, one of the essential genetic pathways involves the gene Huntingtin (HTT), which, when mutated, causes Huntingtons disease, a devastating disorder characterized by the progressive breakdown of nerve cells in the brain.

Tuszynskis team found that the regenerative transcriptome the collection of messenger RNA molecules used by corticospinal neurons is sustained by the HTT gene. In mice genetically engineered to lack the HTT gene, spinal cord injuries showed significantly less neuronal sprouting and regeneration.

While a lot of work has been done on trying to understand why Huntingtin mutations cause disease, far less is understood about the normal role of Huntingtin, Tuszynski said. Our work shows that Huntingtin is essential for promoting repair of brain neurons. Thus, mutations in this gene would be predicted to result in a loss of the adult neuron to repair itself. This, in turn, might result in the slow neuronal degeneration that results in Huntingtons disease.

Co-authors include: Gunnar Poplawski, Erna Van Nierkerk, Neil Mehta, Philip Canete, Richard Lie, Jessica Meves and Binhai Zheng, all at UC San Diego; Riki Kawaguchi and Giovanni Coppola, UCLA; Paul Lu, UC San Diego and Veterans Administration Medical Center, San Diego; and Ioannis Dragatsis, University of Tennesee.

Funding for this research came, in part, from the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the Veterans Administration (Gordon Mansfield Consortium for Spinal Cord Regeneration), the National Institutes of Health (NS09881, EB014986), the Gerbic Family Foundation and the NINDS Informatics Center for Neurogenetics and Neurogenomics (NS062691).

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$2.8 Billion Precision Medicine Software Market by Delivery Mode, Application, End-user and Region – Forecast to 2027 – Yahoo Finance UK

Thursday, April 16th, 2020

Dublin, April 16, 2020 (GLOBE NEWSWIRE) -- The "Precision Medicine Software Market by Delivery Mode (On-premise, Cloud-based), Application (Oncology, Pharmacogenomics, CNS), End User (Healthcare Providers, Research, Academia, Pharma, Biotech) - Global Forecast to 2027 " report has been added to ResearchAndMarkets.com's offering.

The global precision medicine software market is expected to grow at a CAGR of 11.8% from 2019 to 2027 to reach $2.8 billion by 2027.

The growth in the precision medicine software market is mainly attributed to the factors such as paradigm shift in treatment, rising pressure to decrease healthcare costs, scientific & technological advances in the genomics field, and growing focus towards providing companion diagnostics & biomarkers for various therapeutic areas. Moreover, emerging countries and AI in precision medicine provides significant growth opportunities for players operating in the precision medicine software market.

The precision medicine software market study presents historical market data in terms of value (2017, and 2018), current data (2019), and forecasts for 2027 - by delivery mode, application, and end user. The study also evaluates industry competitors and analyzes the market at regional and country level.

On the basis of delivery mode, the on-premise segment accounted for the largest share of the overall precision medicine software market in 2019. However, the web & cloud-based delivery mode segment is expected to grow at the faster CAGR during the forecast period, owing to its benefits, such as on-demand self-serving, no maintenance cost, low storage & upfront cost, and excessive storage flexibility. In addition, the factors such as greater security in private clouds and automated updating features of web and cloud solutions are further expected to support the rapid growth of this segment.

Based on application, the oncology segment accounted for the largest share of the overall precision medicine software market in 2019. However, the pharmacogenomics segment is expected to witness rapid growth during the forecast period. The factors such as increasing incidence of adverse drug reaction, growing focus on genomic-based study, shift from one-size-fits-all approach to personalized approach, and rising pressure on pharmaceutical companies to develop new drugs promote the fastest growth of this segment.

Based on end user, the healthcare providers segment commanded the largest share of the overall precision medicine software market in 2019. However, the pharmaceutical & biotechnological companies segment is expected to witness rapid growth during the forecast period. The factors such as increasing R&D activities related to precision medicine, increasing collaboration between pharma & biotech companies and software vendors, shift from conventional one-size-fits-all-type treatment to precision treatment, and rising R&D costs are the major factors driving rapid growth of this segment.

An in-depth analysis of the geographical scenario of the precision medicine software market provides detailed qualitative and quantitative insights about the five major geographies (North America, Europe, Asia-Pacific, Latin America, and the Middle East & Africa) along with the coverage of major countries in each region.

North America commanded the largest share of the global precision medicine software market in 2019, followed by Europe, Asia-Pacific, Latin America, and the Middle East & Africa. The factors such as well-established healthcare system in the region, rising adoption of technologically advanced products for cancer diagnosis & treatment, growing HCIT investment, government initiatives supporting developments in precision medicine, growing availability of research funding, and higher accessibility to precision medicine software are responsible for the largest share of North America in the precision medicine software market.

The key players operating in the global precision medicine software market are Syapse, Inc. (U.S.), Fabric Genomics, Inc. (U.S.), SOPHiA GENETICS SA (Switzerland), Human Longevity, Inc. (U.S.), Sunquest Information Systems Inc. (U.S.), LifeOmic Health, LLC (U.S.), Translational Software Inc. (U.S.), N-of-One (U.S.), Gene42 Inc. (Canada), PierianDx (U.S.), Foundation Medicine, Inc. (U.S.), and 2bPrecise (U.S.), among others.

Story continues

Key Topics Covered

1. Introduction1.1. Market Definition1.2. Market Ecosystem1.3. Currency1.4. Key Stakeholders

2. Research Methodology

3. Executive Summary

4. Market Insights4.1. Introduction4.2. Drivers4.2.1. Paradigm Shift in Treatment4.2.2. Rising Pressure to Decrease Healthcare Costs4.2.3. Scientific & Technological Advances in the Genomics Field 4.2.4. Growing Focus Towards Providing Companion Diagnostics (CDx) & Biomarkers4.3. Restraints4.3.1. Lack of Awareness about Precision Medicine Practices4.3.2. Fragmented Healthcare Systems in Developing Countries4.4. Opportunities4.4.1. Emerging Economies4.4.2. Artificial Intelligence in Precision Medicine4.5. Challenge4.5.1. Lack of Reimbursement for Genetic Testing & Precision Medicine

5. Global Precision Medicine Software Market, by Delivery Mode5.1. Introduction5.2. On-Premise5.3. Web & Cloud-Based

6. Global Precision Medicine Software Market, by Application6.1. Introduction6.2. Oncology6.3. Pharmacogenomics6.4. Other Applications

7. Global Precision Medicine Software Market, by End User7.1. Introduction7.2. Healthcare Providers7.3. Research and Government Institutes7.4. Pharmaceutical & Biotechnology Companies

8. Geographic Analysis8.1. Introduction8.2. North America8.2.1. U.S.8.2.2. Canada8.3. Europe8.3.1. Germany8.3.2. France8.3.3. U.K.8.3.4. Italy8.3.5. Spain8.3.6. Rest of Europe (RoE)8.4. Asia-Pacific8.4.1. Japan8.4.2. China8.4.3. India8.4.4. Rest of Asia-Pacific (RoAPAC)8.5. Latin America8.6. Middle East and Africa

9. Competitive Landscape9.1. Introduction9.2. Key Growth Strategies9.3. Competitive Benchmarking

10. Company Profiles(Business Overview, Strategic Developments, Product & Service Offering, Financial Overview)10.1. 2bprecise LLC (Part of Allscripts Healthcare Solutions Inc.)10.2. Pieriandx, Inc.10.3. Gene42, Inc.10.4. Foundation Medicine, Inc.10.5. N-Of-One, Inc. (Part of Qiagen N.V.)10.6. Translational Software, Inc.10.7. Syapse, Inc.10.8. Fabric Genomics, Inc.10.9. Sophia Genetics S.A.10.10. Human Longevity, Inc.10.11. Sunquest Information Systems, Inc.10.12. Lifeomic Health, LLC

For more information about this report visit https://www.researchandmarkets.com/r/33bn4y

Research and Markets also offers Custom Research services providing focused, comprehensive and tailored research.

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Chasing the genes behind pain – Knowable Magazine

Thursday, April 16th, 2020

It is a massive, unsolved problem. Chronic pain affects an estimated 50 million to 100 million Americans, disabling up to 20 million of them. And its more than just a noxious physical sensation it affects attention, mood and sleep, even someones relationships and identity. Yet despite the enormous need for better treatments, there are few effective drugs to treat chronic pain beyond opioids, which can be dangerous and addictive. Whats the way ahead?

CREDIT: JAMES PROVOST (CC BY-ND)

Yale School of Medicine and VA Connecticut Healthcare System

The search for better drugs is complicated by the fact that chronic pain takes different forms, and affects the brain as well as where the pain is felt. One strategy is to try to stop pain signals at the source: the nerves that sense damage or threats to the body.

For decades, neurologist and neuroscientist Stephen Waxman has been studying proteins called ion channels that allow these nerve cells to send their signals. Mutations in the genes carrying instructions for these channels give rise to rare pain disorders. These disorders and mutations are pointing the way to new medications for common pain conditions. Waxman, of the Yale School of Medicine and the VA Connecticut Healthcare System, recently coauthored an article about work toward this goal in the Annual Review of Neuroscience. He spoke with Knowable Magazine about the hunt for new pain treatments and the challenges of finding them.

This conversation has been edited for length and clarity.

What is pain, and where does it come from?

Pain is a complex phenomenon. Normal, or nociceptive, pain serves a very important protective and instructive role. If you put your finger near a fire, you immediately pull your finger away. We rapidly learn to avoid things that cause pain.

Nociception originates from receptors located in the peripheral nervous system: the nerves that run through our skin and organs. These receptors are activated by strong mechanical stimuli, noxious heat, noxious cold and noxious chemicals, and the signal is transmitted along nerves. These peripheral nerve fibers carry the pain signal to the spinal cord. There are other neurons within the spinal cord that relay the signal upward to the brain, where pain is recognized.

Now under some circumstances, pain is abnormal. There is a set of conditions, which fall under the term neuropathic pain, where these peripheral neurons fire spontaneously, even when theres no threatening stimulus. It occurs in common disorders like diabetic neuropathy, shingles pain and a complication of cancer treatment called chemotherapy-induced peripheral neuropathy. In these disorders, peripheral pain-signaling neurons become hyperactive: They take on a life of their own and fire when they shouldnt.

Theres also a set of pain disorders that we lump together as inflammatory pain. This pain is a result of damage to peripheral tissues, largely due to inflammation there. And again, this triggers inappropriate firing, which results in chronic pain.

How could understanding these nerve signals lead to new pain treatments?

Nerve cells communicate with each other by producing small electrical impulses. Those depend on the presence of a class of protein molecules called sodium channels. In a sense, you can think of them as tiny molecular batteries in the membrane of nerve cells. And these tiny molecular batteries produce tiny electrical currents that sum up and produce nerve impulses.

For many years, the scientific community talked about the sodium channel, as if there was only one type of sodium channel. As the molecular revolution rolled in, it became clear that there are several types of sodium channels, each encoded by a different gene. It turns out there are nine different sodium channels. We call them Nav1.1, 1.2, all the way through to Nav1.9 [Na for sodium and v for voltage-gated].

Painful stimuli are detected by peripheral sensory nerves called nociceptors (left), which send signals through the spinal cord to the brain, where they are recognized as pain.

CREDIT: MARC PHARES / SCIENCE SOURCE

So could those channels be blocked to relieve pain?

When we go to the dentist, we receive a local injection of novocaine or one of its derivatives. These are sodium channel blockers, and when you receive a local injection into or near the nerves innervating a tooth, theres no pain. But if you took that same drug and put it in the form of a pill, you would also block sodium channels in the heart and brain, so you would get side effects in the central nervous system like double vision, loss of balance, sleepiness and confusion.

So early on, the question arose: Might there be a type of sodium channel that plays a key role in our peripheral nerves, particularly the pain-signaling peripheral nerves, but not in the brain? If those existed, you might be able to turn off pain signaling without central side effects. It turns out that there are three sodium channels that meet the criterion of being peripheral sodium channels; those are Nav1.7, Nav1.8 and Nav1.9.

Finding them was a huge focus of pain research, and now we know they exist. But having a target is just the beginning of the pathway to developing a new set of medications.

A lot of your work on these sodium channels involves people with rare diseases. How do they help our understanding?

In my laboratory, we first investigated people with a genetic disorder called inherited erythromelalgia. Its also known as man on fire syndrome, because these people describe their pain as feeling as if hot lava had been poured into their body, or theyd been scorched with a flame thrower. The pain is triggered by mild warmth that most of us would interpret as almost imperceptible, or certainly not painful.

We discovered that individuals with inherited erythromelalgia all carry mutations in the same gene, the gene that encodes Nav1.7. You can think of the Nav1.7 channel as a volume knob on pain-signaling neurons, and in these individuals the volume knob is turned way up their channels are overactive.

A few years after those families were found, the opposite mutations were found: families with loss-of-function mutations of Nav1.7. These people do not make functional Nav1.7 sodium channels, and they sustain painless bone fractures, painless childbirth, painless tooth extraction, painless burns. But these individuals dont have any other apparent abnormalities of the central nervous system.

Scientists are starting to understand the root causes of certain inherited pain abnormalities. People with a rare genetic disease called inherited erythromelalgia feel pain much more intensely than normal because they carry a mutation that increases the activity of the sodium channel Nav1.7 in pain nerve cells. This causes the nerves to fire more readily. Others, with a congenital insensitivity to pain, carry a defective Nav1.7 sodium channel, so the pain nerves dont fire. People with a third mutation, in the potassium channel Kv7.2, are resilient to pain because the mutation reduces the activity of pain nerves.

So that seems to suggest that, first of all, Nav1.7 is crucial for the sensation of pain?

Thats correct.

And secondly, that these sodium channels are found only or mainly in pain-sensing neurons?

In a broad-brush way, thats correct. There may be small numbers of Nav1.7 channels in particular parts of the brain, but very importantly the individuals with the loss-of-function mutations of Nav1.7 dont have any apparent neurologic abnormalities other than the inability to smell. The clinical studies that have been done on drugs that block Nav1.7 thus far have not yielded substantial side effects related to an effect on the brain.

Are there other rare disorders that might help here, too?

We occasionally encounter people with genetic mutations that should cause very, very extreme pain like mutations in the gene for Nav1.7 that cause erythromelalgia and who for some reason are resilient to developing that abnormal pain, although they still feel normal nociceptive pain. Weve begun to study small numbers of such pain-resilient patients, and in those we have found other genetic variants in certain other genes that confer pain resilience. They do this by turning down the pain response and returning it to near normal.

Again, that may have implications for drug development, because by targeting those genes or the molecules produced by those genes, it may be possible to make an individual pain-resilient to develop medications that will, in a sense, mimic pain resilience.

Can you give any hints about what types of molecules or what types of genes are making people pain-resilient?

Were really excited about a gene that encodes a potassium ion channel called Kv7.2. This channel in a sense acts as a brake on neurons. It lowers their ability to produce nerve impulses and decreases the frequency of nerve impulse firing. In that respect, it acts the opposite to the Nav1.7 channel.

Weve studied one individual in great detail. We know that because of her inherited erythromelalgia, she should have very severe pain but her pain is very, very mild, and its because her Kv7.2 channels are overactive. So this opens up Kv7.2 as a potential target.

Why is it so hard to find new medications for pain?

When youre trying to develop a new drug for cancer, you have biomarkers like blood counts, or you can do various types of scans and measure the size of the cancer. We dont have that for pain we ask patients to rate their pain on a scale from 0 to 10. So we dont have objective measurements.

Another point is that animal studies have not produced drugs that work in people. Finally, people with pain can show a striking placebo response, which of course confounds measurements.

And these issues are superimposed on the general issues of how you develop a new medication. Having a molecule that works in the laboratory gets you only partway there. You have to engineer it into a deliverable form, and you have to make sure the side effect profile is acceptable and the drug is safe. You have to deal with things like dosage, all in a world where clinical trials are very costly, so you dont get to do a lot of them.

When you put it all together, the challenge is immense. Despite that, Im optimistic.

Youve been doing this a long time, and there are a lot of challenges. What keeps you working on this problem?

Part of it is self-serving; its a lot of fun to be a biomedical scientist. But theres also a component that serves others. On my wall I have a picture of two children with inherited erythromelalgia. Weve learned so much from these children and their parents; they have been remarkably generous in sharing their DNA and their stories. The picture is to remind me that were part of a pipeline from the laboratory to society, and there are people depending on us.

On the hard days, when things dont go perfectly well in the laboratory and there are hard days I look at that picture, I show it to my colleagues, and I say, Look, the work were doing matters, its important for people who are depending on us. And thats something I find very motivating.

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Chasing the genes behind pain - Knowable Magazine

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UAE scientists uncover genetic make-up of Covid-19 – The National

Thursday, April 16th, 2020

Scientists in Dubai have uncovered the genetic blueprint of Covid-19, as part of a global effort to understand the virus and develop lifesaving treatments.

Researchers at the Mohammed bin Rashid University of Medicine and Health Sciences (MBRU) completed the first full genome sequencing of the virus to have taken place in the country, after analysing samples taken from a patient in Dubai.

Scientists in other parts of the world have carried out similar work and it is hoped, that by comparing genome sequences from different places, experts will develop an understanding of how the virus mutates and spreads from person to person.

The genetic work will also be invaluable in developing treatments and a vaccine, experts believe.

Scientific research is a critical resource to inform strategies and actions against this virus

Amer Sharif, Mohammed bin Rashid University

Different strains of the virus might behave differently, and this information can also help us put together a picture of how it spreads in the community and throughout the world, Ahmad Abou Tayoun, associate professor of genetics at MBRU, told The National.

We can identify the most prevalent strains and those which require the most surveillance.

Dr Tayoun, who is also director of the Genomics Centre at Al Jalila Childrens hospital in Dubai, said the work could prove especially important in the UAE, given its position as a global travel hub.

In the UAE, we are a meeting point between east and west, so there are multiple different entry points," he said.

"Different viruses have already been sequenced in China, the US and Europe, so it will be interesting to see where we fit in this globally. Do we have just one strain, or all of them?

This work can also help us later on in developing vaccines and making them as effective as possible.

A Civil Defence officer disinfects the streets of Mussaffah using a swivel-mounted high-pressure jet. All photos by Victor Besa / The National

The operation serves two purposes: ensuring traces of the virus, whether on vehicles and dropped masks or gloves, are sterilised, and physically keeping people at home

A police officer asks a resident, who is just out of shot, to go home

Every night for weeks vehicles have sprayed the country with chemicals that kill germs

Abu Dhabi Civil Defence personnel gather for a photo at the start of the night

Crews work all night to cover ground in some of the city's most densely populated areas

Captain Mohammed Al Ahbabi of Abu Dhabi Police speaks to a camera crew from Al Roeya, The National's Arabic-language sister newspaper

Captain Mohammed Al Ahbabi directs a colleague during a sweep of the streets

Civil Defence form the backbone of the street operations

A police officer in a white suit hands out a face mask and gloves to a resident who had none, just before the 8pm curfew begins

The country's leaders have praised public servants for their work around the clock to tackle the virus

The research is important as the genetic blueprint of a virus subtly changes as it mutates.

UK and German researchers have already completed early work on the evolutionary paths of the virus, and have found three distinct "variants" of Covid-19.

The specific strain found in the Dubai patient was most similar to one commonly associated with Illinois, USA, the researchers found.

However, sequencing is to be carried out on virus samples from 240 other patients in the UAE, who became infected at different times in the pandemic, to build a fuller understanding of the situation.

Scientific research is a critical resource to inform strategies and actions against this virus, Amer Sharif, Vice Chancellor of MBRU and head of Dubais Covid-19 Command and Control Centre, said.

We are fortunate to have academic institutions that can join other sectors in Dubai in the fight against Covid-19.

Genome sequencing has increasingly become an important tool for studying disease outbreaks.

The genome of the virus causing Covid-19 consists of 30,000 genetic letters.

Understanding which strain of the virus patients have can help scientists understand how it spreads as, for example, a group of patients found with identical strains are likely to be part of the same cluster.

The work is particularly important as the Covid-19 virus is believed to have originated in animals, and has only recently begun infecting humans.

Scientists believe the virus may still be adapting as part of its shift to infecting people and interacting with human immune systems.

Viruses will accumulate mutations which allow them, for example, to evade immune responses.

"If there is variability in key parts of the virus, it would be incredibly important for vaccine design," Paul Klenerman, a professor at the University of Oxford, recently told the BBC.

In separate studies, the genetics of different people are also being examined to see if this could explain why some coronavirus patients develop no or minor symptoms after becoming infected, while others become critically unwell or die.

In the UAE, the genome research will also look at whether different strains of the disease are more deadly.

This development highlights the critical role of science and the scientific community in enhancing our capacity to fight emerging diseases, said Professor Alawi Alsheikh-Ali, MBRUs provost and a scientific adviser to Dubai authorities.

We will also collect information on the severity of disease in our patients which can help us understand if different strains of the virus are associated with different levels of disease severity.

Updated: April 16, 2020 02:12 AM

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Can genetics explain the degrees of misery inflicted by the coronavirus? – Genetic Literacy Project

Thursday, April 16th, 2020

The single biggest threat to mans continued dominance on the planet is thevirus. Joshua Lederberg, Nobel Prize in Physiology or Medicine, 1958

One of the most terrifying aspects of the COVID-19 pandemic is that we dont know what makes one person die, another suffer for weeks, another have just a cough and fatigue, and yet another have no symptoms at all. Even the experts are flummoxed.

Ive been puzzled from the beginning by the sharp dichotomy of who gets sick. At first it was mostly older people with chronic disease, and then a young person with low risk would show up. It can be devastating and rapid in one individual but mild in another, said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Disease on a media webinar.

What lies behind susceptibility to COVID-19? Gender? Genetics? Geography? Behavior? Immunity? All of these factors may be at play, and they overlap.

Comedian Bill Maher blames poor immunity on eating too much sugar, and a thriving industry pitches immune-boosters, but much of the strength or weakness of an individuals immune response arises from specific combinations of inherited gene variants. Thats my take as a geneticist, and Dr. Faucis. Perhaps genetics and the immune response play a role in why one person has a mild response, yet another rapidly deteriorates into viral pneumonia and respiratory failure, he said.

During the first weeks of the pandemic, the observation that many victims were either older, had certain chronic medical conditions, or both, fed a sense of denial so widespread that young people flocked to Spring Break beaches as older folks boarded cruise ships in Florida as recently as early March. And then the exceptions began to appear among the young people.

While clinicians on the front lines everywhere are saving as many lives as possible, researchers are racing to identify factors that the most vulnerable, and the most mildly affected, share, especially the asymptomatic carriers. And as the numbers continue to climb and more familiar possible risk factors are minimized or dismissed age, location, lifestyle habits genetics is emerging as an explanation for why otherwise young, strong, healthy people can die from COVID-19.

Following are possible genetic explanations for why some people become sicker than others. These are hypotheses, the language of science: ideas eventually fleshed out with observations and data. Proof is part of mathematics; in science, conclusions can change with new data. The public is getting a crash course in the scientific method.

The most obvious genetic risk factor in susceptibility to COVID-19 is being male. The details of disease demographics change daily, but males are about twice as likely to die if theyre infected as are women: 4.7% versus 2.8%.

At first people blamed the sex disparity on stereotypes, like the riskier habits of many a male compared to females. But the sex difference comes down to chromosomes.

In humans, a gene, SRY, on the Y chromosome determines sex. Males have one X and a puny Y; females have two Xs. Fortunately, nature takes care of this fundamental inequality of the sexes, which I detailed hereand in every biology textbook Ive ever written.

To compensate for the X deficit of the male, one X in every cell of a female is silenced beneath a coating of methyl groups, an epigenetic change. But which X is silenced differs, more or less at random. In a liver cell, the turned off X might be the one that the woman inherited from her father; in a skin cell, the silenced X might be the one inherited from her mother.

The immune system seems to benefit from the females patchwork expression of her X-linked genes, with a dual response. Gene variants on one X may recognize viruses, while gene variants on the other X may have a different role, such as killing virally-infected cells.

Women also make more antibodiesagainst several viral pathogens. But some of us pay the price for our robust immune response with the autoimmune disorders that we are more likely to get.

People with type O blood may be at lower risk, and with type A blood at higher risk, of getting sick from SARS-CoV-2, according to results of a recent population-based study. But the idea of type O blood protecting against viral infections goes back years.

We have three dozen blood types. Theyre inherited through genes that encode proteins that dot red blood cell (RBC) surfaces, most serving as docks for sugars that are attached one piece at a time. The RBCs of people with type O blood do not have an extra bit of a sugar that determines the other ABO types: A, B, or AB.

The unadorned RBCs of people with type O blood, like me, are less likely to latch onto norovirus (which explains why I rarely throw up), hepatitis B virus, and HIV.

An investigation of ABO blood types from the SARS epidemic of 2002 to 2003 provides a possible clue to the differences. People with blood types B and O make antibodies that block the binding of the SARS viruss spikes to ACE2 receptors on human cells growing in culture. Since the novel coronavirus enters our cells through the same receptors, are people with type O blood less likely to become infected?

Thats what researchers from several institutions in China have found in the new study. They compared the blood types of 2,173 patients with COVID-19 from three hospitals in Wuhan and Shenzhen to the distribution of blood types in the general population in each area.

People with type A blood were at higher risk than people with type 0 blood for both infection and severity of the illness.

In the general population 31% of the people are type A, 24% are type B, 9% are type AB, and 34% are type O. But among infected individuals, type A is up to 38%, type B up to 26%, AB at 10%, and type O way down to 25%.

The researchers conclude that the findings demonstrate that the ABO blood type is a biomarker for differential susceptibility of COVID-19. I think thats a bit strong for a trend, considering the exceptions. But the researchers suggest that their findings, if validated for more people, can be used to prioritize limited PPE resources and implement more vigilant surveillance and aggressive treatment for people with blood type A.

Immunity and genetics are intimately intertwined. Links between mutations both harmful and helpful and immunity to infectious diseases are well known.

Mutations in single genes lie behind several types of severe combined immune deficiencies (SCIDs), like bubble boy disease. Sets of human leukocyte antigen gene variants (HLA types) have long been associated with increased risk of autoimmune conditions such as celiac disease, type 1 diabetes, and rheumatoid arthritis, and were for many years the basis of tissue typing for transplants.

In HIV/AIDS, two specific mutations in theCCR5 gene remove a chunk of a co-receptor protein to which the virus must bind to enter a human cell. The mutation has inspired treatment strategies, including drugs, stem cell transplants, and using CRISPRto recreate the CCR5 deletion mutation by editing out part of the gene.

Might variants of the gene that encodes ACE2, the protein receptor for the novel coronavirus, protect people in the way that a CCR5 mutation blocks entry of HIV? The search is on.

Another clue to possible genetic protection against the novel coronavirus may come from the SARS experience from years ago and parasitic worm diseases in Africa. (This hypothesis I came up with on my own so Im prepared to be shouted down.)

In a human body, the SARS virus disrupts the balance of helper T cells, boosting the number of cells that fight parasitic worms (the Th2 response) while depleting the cells that protect against bacteria and viruses (the Th1 response). The resulting Th2 immune bias, in SARS as well as in COVID-19, unleashes the inflammatory cytokine storm that can progress to respiratory failure, shock, and organ failure.

In subSarahan Africa alone, a billion people have intestinal infections of parasitic worms, the most common of which is schistosomiasis. Its also called snail fever because the worms are released into fresh water from snails and burrow into peoples feet when they wade in the water.

The worms mate inside our blood vessels, releasing eggs that leave in urine and feces into the water supply. Remaining eggs can inflame the intestines and bladder. The infection begins with a rash or itch, and causes fever, cough, and muscle aches in a month or two. A drug treatment is highly effective.

Genetics determines susceptibility, or resistance to, schistosomiasis. And thats what got me thinking about COVID-19.

People who resist the flatworm infection have variants of eight genes that ignite a powerful Th2 immune response that pours out a brew of specific interferons and interleukins. Could the Th2 immune bias of the novel coronavirus SARS-CoV-2 not be as devastating to people who already have the bias, to resist schistosomiasis? If so, then places in Africa where many people are immune to schistosomiasis might have fewer cases of COVID-19.

So far parts of Africa have reported low incidence of the new disease. On April 7, the World Health Organization reported approximately 10,000 cases in all of Africa. Thats similar to the number of deaths in New York City, although Africa could be on track for the exponential growth seen elsewhere. But if the lower number in Africa persists, then maybe those eight genes are protecting people. Adding to the evidence is that the 8-gene set varies more between West Africans and Europeans than do other sets of genes.

Like the ABO blood type study, if the 8-gene signature that protects against schistosomiasis protects against COVID-19, then the signature should be overrepresented among those exposed to the virus who do not get very sick, and underrepresented among those who do. However, its possible that Africa is just behindthe rest of the world in reporting COVID-19 cases. So, a thought experiment for now.

Before researchers zero in on a highly predictive genetic signature of COVID-19 risk, we can think about how the information would best be used:

I hope that discovery of a genetic basis for COVID-19 vulnerability or resistance will not inspire discrimination unfortunately, genetic information has had a legacy of misuse.

Ricki Lewis is the GLPs senior contributing writer focusing on gene therapy and gene editing. She has a PhD in genetics and is a genetic counselor, science writer and author of The Forever Fix: Gene Therapy and the Boy Who Saved It, the only popular book about gene therapy. BIO. Follow her at her website or Twitter @rickilewis

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Can genetics explain the degrees of misery inflicted by the coronavirus? - Genetic Literacy Project

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California university researchers join the global race to fight coronavirus – EdSource

Thursday, April 16th, 2020

Courtesy of UC Davis Health

UC Davis scientists Marcelo Prado and Katie Zegarski load samples onto trays that will then be placed into a machine to test for coronavirus. It's one example of the vast research ongoing across the UC system to study the coronavirus.

UC Davis scientists Marcelo Prado and Katie Zegarski load samples onto trays that will then be placed into a machine to test for coronavirus. It's one example of the vast research ongoing across the UC system to study the coronavirus.

Researchers at universities across California are playing a major role in the global effort to find a cure and slow down the spread of the novel coronavirus.

The University of California, with five medical centers and major research capacity on its 10 campuses, is well-positioned to contribute to that effort, while private universities like Stanford University, with its ownresearch departments and medical school, are also working to understand and treat the disease.

With non-essential research suspended, many scientists are focused almost exclusively on fighting the virus and are doing so in a variety of ways. Doctors are working to increase the capacity to test individuals for coronavirus while also evaluating drugs to determine if they can be used as effective treatments. Virologists are studying the genetics of the virus to learn more about how it spreads and attacks human cells. There are also more niche efforts, such as a project at UC Berkeley that intends to use artificial intelligence to combat the virus.

There is an urgent need for scientists to learn as much as possible about the virus and slow its spread. Globally, the toll from the coronavirus has surpassed 116,000 deaths, according to a Johns Hopkins University tracker. That includes more than 300 deaths in California.

One of the leading sites for coronavirus research in California is at UC Davis, wheremany researchers have been studying the virus nonstop since February. Thats when the universitys medical center treated the patient who had the first diagnosed case of community spread coronavirus in the United States, meaning the patient, who had not traveled to countries where the virus was common at that time, had been infected from someone in the community.

Researchers took samples from that patient and used them to investigate the virus and begin developing their own in-house test.

The university was equipped to study the virus because of its range of research and medical centers, said Angela Haczku, who, as the associate dean for translational research at UC Daviss School of Medicine, oversees the universitys coronavirus research. The School of Medicine collaborated with the universitys Center for Immunology and Infectious Diseases and the universitys primate research center to create their own tests. The universitys primate center, where experiments are conducted using non-human primates, could also eventually be used to test and develop potential vaccines, officials said.

UC Davis began in-house testing March 19 and is now using an automated testing system that has the potential to produce more than 1,000 tests daily, Haczku said. There is a shortage of coronavirus testing nationally, and experts say that expanding testing would make it easier to slow the spread of the virus since doctors would have a better idea of who is infected.

The automated testing at UC Davis is made possible through a robot called the Roche Diagnostics cobas 6800 System. The machine, which is the size of an SUV, is already producing 400 tests a day for patients at UC Davis Health and that number could increase to up to 1,400 tests daily.

Haczku said she has dedicated almost all of her time over the past month to coronavirus-related research focused on expanding testing and on clinical trials, which involve testing drugs on patients to learn if they can work as effective treatments. UC Davis is currently conducting clinical trials of two drugs: remdesivir, an antiviral drug that was previously tested on patients with Ebola, and sarilumab, which treats arthritis.

Haczkus days start with 7 a.m. meetings with other School of Medicine administrators and end around midnight after connecting with research collaborators in Asia.

Seeing what this virus does to people, there is a motivation to work fast, she said.

Courtesy of UC Davis Health

A scientist at UC Davis tests a patient sample for coronavirus.

The other four University of California medical centers at UCLA, UC San Diego, UCSF and UC Irvine are also either doing their own in-house testing of the coronavirus or plan to soon. The five medical centers hope to combine resources, such as patient databases, to develop better testing and clinical trial capabilities, but they first need to get approval from a UC Institutional Review Board, Haczku said. Institutional Review Boards are regulatory committees that oversee research involving humans to make sure the research is ethical.

Globally, more than 200 clinical trials of different drugs are underway. One of those trials involves all five of the UC campuses with medical centers. They are among dozens of universities conducting a trial of remdesivir, an antiviral drug that scientists believe has potential to be a treatment for the virus. Stanford University is also participating in that trial. In clinical trials, drugs are administered to patients who give consent to participate in the trial after learning about any potential risks.

Dr.Bruce Aylward of the World Health Organization in February called remdesivir the one drug right now that we think may have real efficacy. President Donald Trump has also touted remdesivir, saying in March that the drug seems to have a very good result having to do with this virus.

However, remdesivir is not yet an approved treatment of COVID-19, the disease the virus causes. The Food and Drug Administration has authorized its use in emergency situations for some coronavirus patients, including the first United States patient who was diagnosed with coronavirus and the UC Davis patient who was diagnosed with the first community-acquired case of the virus in the U.S. UC Davis doctors in February gave the drug to that patient, who recovered after receiving remdesivir and has since been discharged, though doctors have warned against drawing conclusions about the drug based on a single patients experience.

Doctors will get a better sense of whether the drug is effective through the clinical trials. Patients will be eligible to be enrolled in the clinical trial if they test positive for COVID-19 and if they are being treated at one of the testing sites, such as one of the UC medical centers or Stanford.

Patients will be randomly assigned to receive either remdesivir or a placebo. The National Institutes of Health, the federal agency that is sponsoring the trial, will analyze results from the different testing sites and determine whether the drug is effective, said Dr. Neera Ahuja, who along with Dr. Kari Nadeau is one of two Stanford doctors conducting the trial.

A major advantage of the study, Ahuja said, is that if remdesivir proves to be ineffective, doctors can continue with the same trial infrastructure and easily switch to testing another drug. Thats because the study has an adaptive trial design, which is meant to make a trial more efficient by allowing changes to the study while it is ongoing.

And so unlike some of the other industry-sponsored trials where its just one drug and thats all they have, we can phase from one to the next to the next until we hopefully find something effective and then be able to hopefully fast track it to FDA approval, Ahuja told EdSource.

Remdesivir is far from the only drug being studied to fight the coronavirus.

Researchers at UC San Franciscos Quantitative Sciences Bioinstitute are looking into dozens of other drugs that could attack the virus in a different way.

While drugs like remdesivir seek to destroy the viruss own proteins, researchers at the Quantitative Sciences Bioinstitute have identified drugs that could potentially treat the virus by blocking it from interacting with proteins in human cells that the virus relies on to survive.

Theres a lot of work ongoing where people are trying to target the viral proteins, which is great. Were taking a different track, Nevan Krogan, the director of the institute, said at a virtual town hall in March.

So far, they have identified 69 drugs that could target the human proteins, including 27 that are FDA-approved.

The reason scientists are studying so many different drugs is because the current coronavirus is new to scientists and there is still much they dont know about it.

Virologists like Mike Buchmeier at UC Irvines Center for Virus Research are attempting to address that dilemma by studying exactly how the virus is spreading.

Buchmeier, who specializes in researching coronaviruses, has been researching the virus since it was discovered in China in December. Officially called SARS-CoV-2, it is a new strain of coronavirus, which is part of a large family of viruses that commonly infect many animals, including cats, cattle and bats.

In rare cases, such as with the current virus, coronaviruses can spread from animals to humans and then spread to other people, according to the Centers for Disease Control and Prevention. Health experts believe the new strain of coronavirus likely originated in bats and first spread from animals to humans at a seafood and meat market in Wuhan, China, where the outbreak began.

Buchmeiers current research, he said in an interview, involves studying the viruss RNA, a single stranded genetic material. (Many viruses have RNA instead of the double stranded DNA genetic material.) Having that information helps Buchmeier and other scientists understand the virus because they can use the genetic material to trace the origins of the virus and how it has spread. The genetic material also allows Buchmeier to better understand how the virus causes damage in humans.

And then we can use that to think about what would be a suitable vaccine, Buchmeier said.

Elsewhere across universities in California, other efforts are underway in response to the virus. For example, UC Berkeley is one of the hosts of a new artificial intelligence research consortium that is seeking research proposals that offer ways to fight the coronavirus.

The consortium, called the C3.ai Digital Transformation Institute, was created by California-based artificial intelligence company C3.ai and will be managed and hosted by UC Berkeley and the University of Illinois at Urbana-Champaign. One of the institutes co-directors is Shankar Sastry, a professor of engineering and computer science at UC Berkeley.

Early results from the research wont be available until June, but the work of other artificial intelligence companies internationally may provide a glimpse into how the technology can be used to fight the virus.

For example, the United Kingdom-based artificial intelligence company Exscientia has a collection of thousands of drugs and is using its technology to try to determine which ones can potentially treat COVID-19. Exscientia plans to use its drug-screening technology to quickly mine through the drugs and identify molecules that may be effective in fighting the coronaviruss proteins and enzymes. The company then hopes to use that information to repurpose one of the existing drugs to treat coronavirus patients.

The Berkeley institute is calling for a wide range of proposals to combat the virus, such as using machine learning to design new drugs or incentivize behavior that mitigates the spread of the virus, like social distancing.

Given the urgency of the challenge, the institute accelerated its timeline by putting out the first call for research proposals in March and asked for the proposals to be submitted by May 1. Awards will be distributed by June, but researchers who submit their proposals by April 15 could be notified of awards earlier than that.

The institute also plans to use a peer-review process that is less rigorous than is customary so it can further expedite the project and share results with the public as soon as possible. The consortium plans to start disseminating results via public forums in June. What wed like to do here is to provide for a certain adventurousness. We wont be afraid to have even a substantial fraction of the research projects fail, he said.

Sastry added that he views the institute as something that could be an intermediary between the computer science world and the public health field.I feel theres a huge new subject of academic inquiry here. And so I think that to have an intermediary between information technologies and all these societal systems, I think thats the intellectual turf of this institute. Thats really a prime excitement to me, Sastry said.

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UNM researchers use advanced computing to study COVID-19 – UNM Newsroom

Thursday, April 16th, 2020

A wide range of University of New Mexico researchers from across main and north campuses are utilizing UNM Center for Advanced Research Computing resources to study COVID-19. Researchers from several departments at UNM, including Anthropology, Biology, Computer Science, Pediatrics, Internal Medicine, and various Health Sciences research centers are studying different aspects of the coronavirus pandemic.

Since the U.S. discovered its first case of COVID-19 on in January, scientists across the country have worked feverishly to understand this new and rapidly spreading disease. A collaborative team of researchers including assistant professor at the UNM Center for Global Health Daryl Domman, assistant professor at the UNM Department of Pediatrics Darrell Dinwiddie, professor at the UNM Division of Translational Informatics Tudor Oprea, and biologists at the Los Alamos National Laboratory have been using advanced computing techniques to study the genetic variations of SARS-CoV-2, the virus that causes COVID-19. By sequencing the genome of SARS-CoV-2 samples taken from positive cases in New Mexico and Wyoming, the team has been able to track mutations in the virus.

Oprea explained, Were trying to understand what the trends are with respect to the viruswhether its the same virus that came from Wuhan, or, does it mutate? How many flavors of the virus are out there? Do they cause different symptoms?

Tracking the locations of precise coronavirus strains allows researchers like Domman to understand exactly how the novel coronavirus is spreading.

What were hoping to do with this information is really understand the spread of the virus within our community, Domman reported. He explains, Traditional epidemiology is about case count datalooking at contact tracing and who might have been exposed. This data is extremely useful but its inherently limited in answering questions about how the virus is spreading.

Looking at which genetic variations of SARS-CoV-2 appear in specific locations can provide additional information beyond counting the number of positive cases in a region. Domman believes that sequencing samples of the novel coronavirus will allow scientists to identify local transmission chains, estimate how long the virus has existed within a community, and estimate how many cases are currently active within a region. Already, this project has revealed important insights into the local spread of coronavirus, including that the vast majority of early COVID-19 cases in New Mexico and Wyoming can be attributed to European travel.

Meanwhile, the New Mexico Decedent Image Database (NMDID), since its website launch in January of this year, has already been a source of valuable information for COVID-19 research. The NMDID is a free resource that gives researchers access to over 15,000 decedent full-body CT scans and a wealth of information about the deceased. CARC houses and maintains the database in collaboration with UNM associate professor of Anthropology and creator of NMDID Heather Edgar. Researchers at Johns Hopkins University have been using NMDID to better understand how COVID-19 affects its victims.

Edgar said, Theyre using about 34 or so CTs of decedents who died of pneumonia and comparing [them] to people who have COVID-19basically looking to see how similar or different the new disease is to the things were used to looking at.

Across campus at the UNM Moses Biological Computation Lab, Computer Science and Biology professor Melanie Moses and research assistant Vanessa Surjadidjaja are using CARC resources to understand how the human lung responds to a viral pathogen like SARS-CoV-2.

Currently, there is much to learn about how our immune systems are responding to the novel coronavirus. Our research aims to understand how the immune system, specifically T cells, find cells infected with SARS-CoV-2 dispersed in the lung, Surjadidjaja explained. Their study uses laboratory data and computer simulations to visualize interactions between immune cells and viruses within the complex structures inside the lung. Their goal is to predict how viral load changes over the course of an infection, an important component of disease severity and transmissibility between people.

All of these studies are ongoing and will continue to develop quickly as scientists do their best to make a positive impact during this tumultuous time.

Oprea captured the current mood of many research teams when he said, Everyone works with a sense of urgency. We are well aware that until a vaccine is found, the world will be in stand-by mode. Were just trying to do our part.

Domman stressed the importance of providing local authorities with the information they need to make prudent policy choices, commenting, In the more immediate, its about providing that actionable data to the folks who will do some good with it.

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New CRISPR-Based COVID-19 Test Kit Can Diagnose Infection in Less Than an Hour – UCSF News Services

Thursday, April 16th, 2020

Transmission electron micrograph of the SARS-CoV-2 virus. Image credit: NIAID

Scientists have developed an inexpensive new test that can rapidly diagnose COVID-19 infections, a timely advance that comes as clinicians and public health officials are scrambling to cope with testing backlogs while the number of cases continues to climb.

Developed at UC San Francisco and Mammoth Biosciences, the new test officially named the SARS-CoV-2 DETECTR is easy to implement and to interpret, and requires no specialized equipment, which is likely to make the test more widely available than the current crop of COVID-19 test kits. Though the new test has yet to receive formal approval for clinical use from the U.S. Food and Drug Administration, UCSF researchers are clinically validating the test in an effort to fast-track the approval process through a so-called Emergency Use Authorization.

The introduction and availability of CRISPR technology will accelerate deployment of the next generation of tests to diagnose COVID-19 infection, said Charles Chiu, MD, PhD, professor of laboratory medicine at UCSF and co-lead developer of the new test, which is described in a paper published April 16, 2020, in the journal Nature Biotechnology.

The new SARS-CoV-2 DETECTR assay is among the first to use CRISPR gene-targeting technology to test for the presence of the novel coronavirus. Since CRISPR can be modified to target any genetic sequence, the test kits developers programmed it to home in on two target regions in the genome of the novel coronavirus. One of these sequences is common to all SARS-like coronaviruses, while the other is unique to SARS-CoV-2, which causes COVID-19. Testing for the presence of both sequences ensures that the new DETECTR tool can distinguish between SARS-CoV-2 and closely related viruses.

Much like the diagnostic kits currently in use, the new test can detect the novel coronavirus in samples obtained from respiratory swabs. However, the new test is able to provide a diagnosis much more quickly. While the widely used tests based on polymerase chain reaction (PCR) techniques take about four hours to produce a result from a respiratory sample, the new DETECTR test takes only 45 minutes, rapidly accelerating the pace of diagnosis.

Another key advantage of the new DETECTR test is that it can be performed in virtually any lab, using off-the-shelf reagents and common equipment. This stands in stark contrast to PCR-based tests, which require expensive, specialized equipment, limiting those tests to well-equipped diagnostic labs. Plus, the new DETECTR test is easy to interpret: much like a store-bought pregnancy test, dark lines that appear on test strips indicate the presence of viral genes.

The new test is also highly sensitive. It can detect the presence of as few as 10 coronaviruses in a microliter of fluid taken from a patient a volume many hundreds of times smaller than an average drop of water. Though slightly less sensitive than existing PCR-based tests, which can detect as few as 3.2 copies of the virus per microliter, the difference is unlikely to have a noticeable impact in diagnosis, as infected patients typically have much higher viral loads.

The SARS-CoV-2 DETECTR adds to a rapidly growing suite of new COVID-19 diagnostic tests that researchers and clinicians hope will increase testing capacity, including tests for specific antibodies in patients who have recovered from COVID-19 infection.

As researchers work to validate the new DETECTR test for FDA approval, its developers are continuing to make modifications to the test kit so that it can be used for field testing at sites like airports, schools, and small clinics.

Authors: James PBroughton of Mammoth Biosciences and Xianding Deng of UCSF are co-lead authors of the study. Charles Chiu of UCSF and JaniceChen of Mammoth Biosciences are co-senior authors of the study. Additional authors include Guixia Yu, Venice Servellita, Jessica Streithorst, AndreaGranados,AliciaSotomayor-Gonzalez, AllanGopez, ElaineHsu, WeiGu, and SteveMiller, and Kelsey Zorn, of UCSF; Clare LFasching, JasmeetSingh, and Xin Miao of Mammoth Biosciences; and Chao-YangPan,HugoGuevara,and DebraWadford of the California Department of Public Health.

Funding: This work was supported by National Institutes of Health (NIH) grants R33-AI129455 from the National Institute of Allergy and Infectious Diseases and R01-HL105704 from the National Heart, Lung, and Blood Institute; the Charles and Helen Schwab Foundation; and Mammoth Biosciences, Inc.

Disclosures: Chiu is the director of the UCSF-Abbott Viral Diagnostics and Discovery Center (VDDC), receives research support funding from Abbott Laboratories, and is on the Scientific Advisory Board of Mammoth Biosciences, Inc. Chen is a co-founder of Mammoth Biosciences, Inc. Broughton, Fasching, Singh, and Miao are employees of Mammoth Biosciences, Inc. Chiu, Broughton, Deng, Fasching, Singh, Miao and Chen are co-inventors of CRISPR-related technologies.

About UCSF: The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. UCSF Health, which serves as UCSF's primary academic medical center, includes top-ranked specialty hospitals and other clinical programs, and has affiliations throughout the Bay Area.

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The Pursuit of Knowledge | UVM Today | The – UVM News

Thursday, April 16th, 2020

For students at the University of Vermont, knowledge knows no bounds. Near or far from campus, they study everything from the most complex micro-ecosystems on the planet to the biggest threats to democracy today; they're engaged year-round, day and night, all in pursuit of knowledge. As this academic year enters its final stretch, we take a look at some of the most exciting research projects UVM students have worked on this year.

Want more? Hundreds of student research projects from every discipline are ready to discover at the Virtual Student Research Conference. Engage with student researchers online from Thursday, April 16, to Thursday, April 23.

According to animal science student Jamie Burke 20, pictured above, the inside of a cows stomach contains one of the most complex micro-ecosystems in the world. She would know, as shes helped create and sustain six artificial cow rumens in Professor Sabrina Greenwoods lab in the College of Agriculture and Life Sciences.

To better understand how introducing amino acid supplements into a cows diet might ultimately improve health and nutrition properties in dairy products, Burkewith guidance from professor Jana Kraftfed and maintained fermenters that mimicked the activity that takes place inside a cow's stomach.She and the research team in Krafts lab specifically analyzed the branched-chain fatty acids (BCFA) in protozoal cell membranes in the artificial rumen ferment.

But they had one hiccup: in a real rumen, most protozoa like to attach to the rumen wall; in an artificial rumen, that hospitable surface doesnt exist. So, Burke 3D printed a filter for the ferment. This 3D-printed support can serve as a model for all continuous culture fermenter systems to promote protozoa retention, maintain fluid flow, and allow for better comparisons of protozoa numbers in different systems, she says.

Preparing for a weekend ahead, Danielle Allen makes sure the cells she's growing in the Thali lab for her HIV research will stay "happy and healthy" until Monday when she returns. (Video: Rachel Leslie)

Viruses are absolutely fascinating, says molecular genetics senior Danielle Allen, who is conducting research on the spread of HIV at the cellular level in Professor Markus Thalis lab at the College of Agriculture and Life Sciences. Allens research is focused on one of the relevant host proteins, EWI-2, active in cell fusion, which can occur when a viral protein in an HIV-infected cell binds to a surface protein on an uninfected cell. EWI-2 is also an active component in other biological functions, including cancer metastasis, sperm-egg fusion and muscle regeneration. But while it is a known fusion inhibitor, the proteins mechanism of fusion inhibition is not well understood.

Thats where Allen set her sights. Using fluorescence microscopy, she determined optimal transfection conditions for EWI-2 mutant plasmids to obtain equal surface expression of each EWI-2. Allen also designed a new fusion assay system that could be used for future fusion assays to further characterize EWI-2s mechanism of fusion inhibition.

By understanding these proteins involved in HIV transmission, we might be able to develop better treatments for HIV, which is really important since the current treatments are intense and there isnt a cure, says Allen. Ive learned a lot of different techniques that I didnt know beforeeverything from growing DNA in E. coli to isolating the DNA, transfecting HeLa cells, a lot of stuff with florescence microscopy and staining cells with antibodiesa lot of stuff you just dont really have time to learn in lectures in undergraduate teaching labs.

Political science and history double major Jason Goldfarb. (Photo: Sally McCay)

Jason Goldfarb 20 grew up hearing about the ways social media connected the world, exposing truths in the Arab Spring and elevating causes like the Black Lives Matter movement. But headlines of Russian propagandists and Cambridge Analytica following the 2016 U.S. election prompted Goldfarb to wonder: is social media helping or harming us? In the seniors thesis project for the College of Arts and Sciences, Scrolling Alone: The Impact of Social Media on American Democracy, he outlines a disturbing finding: Although there is potential for social media to live up to its promise of connecting the world, the present platforms harm civic discourse, Goldfarb says.

A double major in political science and history, his research considers technology through both lenses, drawing parallels between Facebook and other revolutionary technologies throughout time. Think of the automobile, notes Goldfarb. It democratized transportation, revolutionized warfare, and changed the way in which cities are designed. Social media, he argues, has similarly transformed much of todays world, stoking polarization, encouraging distraction, and eroding privacy. The paper was published in the Undergraduate Journal of Politics, Policy and Society in late 2019. Under the guidance of Dr. Amani Whitfield and Professor Bob Pepperman Taylor, its my proudest accomplishment at UVM.

Anthropology major Rose Lillpopp. (Photo: Sally McCay)

From University Row to upscale private events, it seems like food trucks can be found everywhere these days. Though lauded as an entrepreneurial feat for the past decade, College of Arts and Sciences anthropology student Rose Lillpopp 20 says that food trucks have historical roots and repercussions in the street food vending industry that run deep. Her research digs into the positive and negative influences food trucks have on our foodways and social relationships, and grapples with topics like immigration, identity, race, class and public policy.

In addition to sampling the menus of dozens of food trucks, Lillpopp developed relationships with vendors and customers she interviewed about how a vendors authenticity or legitimacy is earned, how their brands are perceived and what customers convey about themselves when they order in public spaces.

For example, Customers patronizing a vegan truck versus a wagyu beef truck are claiming different identities that come with various moral or economic prestige, she explains. Because food trucks have been under-researched and taken for granted, this conflicted history is erased by the fallacy that the gourmet food truck is unattached to these less privileged forms of vending.

Business student Mateo Florez. (Photo: Sally McCay)

While much about the use and effects of e-cigarettes remain unknown, entrepreneurship and marketing student Mateo Florez 20 is searching for answers about why these vaping products are so popular among college students.

For his Grossman School of Business research, he collected data from 750 undergraduate students about their basic demographics, substance use and preferences to run a statistical analysis technique, called a conjoint analysis. Ultimately, the analysis will provide insight on the relative value each respondent places on certain attributes of vapingincluding social context while vaping, substance effect from vaping and health risksand will be able to establish a possible correlation between demographics and e-cigarette use.

E-cigarettes have exploded in popularity during the past couple years, and understanding more about the driving forces behind e-cigarette consumption can provide both policymakers and consumers better insight into the root causes of this trend, he says.

Hannah Sheehy (center) teaches fellow student research assistants about a new rubric she developed to measure the quality of the childrens storytelling. (Video: Janet Franz)

Not all research endeavors result in storybook endings, but for the families that Hannah Sheehy and Provost Patty Prelock collaborated with for a study about Theory of Mind (ToM)the ability to attribute mental states to oneself and others, one of the primary challenges of autism spectrum disorder (ASD)its been just that.

As a research team coordinator for Prelocks study, Sheehy,a communication sciences and disorders senior in the College of Nursing and Health Sciences, assisted three families with ASD children throughout a six-week reading intervention program designed to help bolster their students ToM. The intervention program incorporated parent-led stories and picture books with ToM elements such as visual perspective-taking and emotion recognition, and included scripts to help parents further facilitate discussion with their child about the stories. Sheehy collected and analyzed the data from the program and found that each child improved not only their ToM score, but their own language complexity and story coherence abilities as well.

Pointing out a characters facial expression or asking the child how they think a character is feeling helped the children understand peoples emotions and become stronger storytellers themselves, which is an important social skill, says Sheehy. Ive loved seeing how the study empowers parents to incorporate simple book-reading strategies that scaffold their childs ToM development into their everyday lives and conversations.

Business student Michael Chan. (Photo: Sally McCay)

Recognizing the increasing demand for sustainable and socially responsible businesses and products,Michael Chanwas curious about how that trend found its way into local communities. A double major in business and environmental sciences, Chans research looked to an unexpected source for answers: marginalized small business owners. Small businesses are key change agents in their communitys transformation toward a more sustainable future, he says.

Chan conducted personal interviews with local entrepreneurs of varying genders, geographic locations, races, industries and sizes about how they started and grew their businesses. He then analyzed major trends among their experiences by applying constructivist grounded theory to their narratives. What he noticed was that, despite their identity and industry differences, major themes of family, resilience and care for others emerged, connecting identity groups.

Storytelling is a powerful tool in changing the world around us, Chan says. When it comes to building a more sustainable and socially responsible future, his findings indicate that connecting to the experiences of those deemed other in our communities will increase awareness of our individual purchasing power.

Medical Laboratory Science major Sierra Walters maintains cancer cell lines for genetic experiments. Her work contributes to a project investigating the alterations of a gene associated with lung cancer, the leading cause of worldwide cancer-related mortality. (Video: Janet Franz)

How to tell if a malignant tumor will be responsive to treatment? In her time at UVM, senior Sierra Walters has worked to help researchers better answer that question. Specifically, a team working with College of Nursing and Health Sciences professor Paula Deming and Larner College of Medicine professor David Seward is taking a closer look at a protein, STK11, thats been implicated in certain types of lung cancer and can equate to a poor prognosis. The big picture to this project is to study how different genetic variations in the STK11 gene alter the proteins function, explains Walters, with the hope of someday aiding doctors and labs profiling the tumors of lung cancer patients. Im so grateful to have gotten involved in this project so early in my college career, says Walters, a medical laboratory science major in the College of Nursing and Health Sciences. While the research is on pause during remote instruction, the team still meets weekly. And her time at UVM isnt done; after graduation, Walters will pursue her masters, and work in the microbiology department at UVM Medical Center. Having a hands-on job where Im constantly trying new things and working with other students in the lab helped prepare me for the future.

Writing for this piece contributed by Kaitie Catania, Andrea Estey, Janet Franz and Rachel Leslie. Photos by Josh Brown and Sally McCay. Videos by Janet Franz and Rachel Leslie.

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Clinical Cancer Research Highlights Potent Antitumor Activity of Repotrectinib in Treatment-Nave and Solvent-Front Mutation Ros1-Positive Non-Small…

Thursday, April 16th, 2020

SAN DIEGO, April 16, 2020 (GLOBE NEWSWIRE) -- Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, today announced the publication of preclinical data and patient case studies from the Phase 1 portion of its TRIDENT-1 clinical study for its lead investigational drug, repotrectinib.

Among the findings published in the American Association of Cancer Research peer-reviewed journal, Clinical Cancer Research, repotrectinib demonstrated potent in vitro and in vivo activity in patient-derived preclinical models compared with proxy chemical compounds for other tyrosine kinase inhibitors (TKIs) against ROS1 and the ROS1 G2032R solvent-front mutation. The central nervous system (CNS) activity of repotrectinib was studied in an in vivo model and demonstrated significant reduction of metastatic brain lesions with longer survival compared to a proxy chemical compound for entrectinib.

Our findings provide encouraging support for repotrectinib as a potential first-line treatment in ROS1-positive non-small cell lung cancer, and later-line use after progression from a prior ROS1 TKI, said Dr.Byoung Chul Cho,Division of Medical Oncology, Yonsei Cancer CenteratSeverance Hospital,Yonsei University College of Medicine,Seoul,Republic of Korea and corresponding author of the paper. In addition, these preclinical data as presented initially at the annual AACR conference in 2019 and now expanded upon in the publication suggest repotrectinib may prevent or delay the emergence of the G2032R solvent-front mutation and subsequent compound mutations, potentially improving clinical outcomes.

In preclinical studies, repotrectinib potently inhibited in vitro and in vivo tumor growth and ROS1-downstream signaling in treatment-nave models compared with proxy chemical compounds for crizotinib, ceritinib, and entrectinib. Compared to a lorlatinib proxy chemical compound in a xenograft model, repotrectinib markedly delayed the onset of tumor recurrence following drug withdrawal. In addition, repotrectinib induced anti-tumor activity in the CNS. Repotrectinib also showed selective and potent in vitro and in vivo activity against the ROS1 G2032R solvent-front mutation.

Patient case studies (from the previously reported July 22, 2019 data cut-off) included in the manuscript highlighted the potential for repotrectinib to prevent or delay ROS1 kinase domain resistance mutations.

The emergence of resistance mutations and disease progression in the CNS are characteristics of ROS1-positive non-small cell lung cancer and represent a high unmet medical need given the lack of approved therapies, said Dr. Mohammad Hirmand, chief medical officer of Turning Point Therapeutics. These findings highlighted in Clinical Cancer Research build on prior preclinical studies of repotrectinib and data we have shown from the Phase 1 portion of TRIDENT-1, and are encouraging for repotrectinib as a potential treatment for both TKI-nave and -pretreated ROS1-positive non-small cell lung cancer patients.

Approximately 50 to 60 percent of crizotinib-resistant mutations are found within the ROS1 kinase, of which the ROS1 G2032R solvent-front mutation is the most common. In addition, it is estimated that approximately 50 percent of patients treated with ROS1-TKIs experience disease progression due to CNS metastases.

The Clinical Cancer Research article may be found online at https://clincancerres.aacrjournals.org/content/early/2020/04/08/1078-0432.CCR-19-2777

More information about the ongoing TRIDENT-1 study of repotrectinib may be found by searching clinical trial identifier NCT03093116 at https://clinicaltrials.gov.

About Turning Point Therapeutics Inc.Turning Point Therapeuticsis a clinical-stage precision oncology company with a pipeline of internally discovered investigational drugs designed to address key limitations of existing cancer therapies. The companys lead drug candidate, repotrectinib, is a next-generation kinase inhibitor targeting the ROS1 and TRK oncogenic drivers of non-small cell lung cancer and advanced solid tumors. Repotrectinib, which is currently being studied in a registrational Phase 2 study in adults and a Phase 1/2 study in pediatric patients, has shown antitumor activity and durable responses among kinase inhibitor treatment-nave and pre-treated patients. The companys pipeline of drug candidates also includes TPX-0022, targeting MET, CSF1R and SRC, which is currently being studied in a Phase 1 trial of patients with advanced or metastatic solid tumors harboring genetic alterations in MET; TPX-0046, targeting RET and SRC, which is currently being studied in a Phase 1/2 trial of patients with advanced or metastatic solid tumors harboring genetic alterations in RET; and TPX-0131, a next-generation ALK inhibitor entering IND-enabling studies. Turning Points next-generation kinase inhibitors are designed to bind to their targets with greater precision and affinity than existing therapies, with a novel, compact structure that has demonstrated an ability to potentially overcome treatment resistance common with other kinase inhibitors. The company is driven to develop therapies that mark a turning point for patients in their cancer treatment. For more information, visit http://www.tptherapeutics.com.

Forward Looking StatementsStatements contained in this press release regarding matters that are not historical facts are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the efficacy, safety and therapeutic potential of Turning Point Therapeutics drug candidate repotrectinib, and the results, conduct, and progress of Turning Point Therapeutics TRIDENT-1 clinical study of repotrectinib. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as plans, will, believes, anticipates, expects, intends, goal, potential and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Turning Point Therapeutics current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with Turning Point Therapeutics business in general, and the other risks described in Turning Point Therapeutics filings with the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Turning Point Therapeutics undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

Jim Mazzolajim.mazzola@tptherapeutics.com858-342-8272

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Without state’s help, OSU lab found its own way to help COVID-19 testing – Salem Reporter

Thursday, April 16th, 2020

The Oregon State University veterinary laboratory teamed up with a private lab to use its expertise to boost testing and tracking of the COVID-19 virus, even after its offer of help drew scant interest from state health officials.

(CDC file art)

Published by arrangement with The Lund Reporthttps://www.thelundreport.org/

Specialists at Oregon State Universitys veterinary laboratory figured they could help the state ramp up testing for coronavirus. They run a sophisticated facility with state-of-the-art testing equipment, and theyre experts atdiagnostics and tracking viruses.

But they couldnt just start running COVID-19 tests. They faced a tangle of red tape.

So they approached the Oregon Health Authority, and a lawmaker contacted Gov. Kate Browns office for help. That led nowhere. The authority did not give them any support, and Browns office did not follow up with them, according to interviews and documents obtained by The Lund Report.

The labs managers did not give up. They forged ahead, dismantling obstacles without the states help. They joined forces with a commercial medical lab in Corvallis. In a joint effort, the two labs plan to launch their first COVID-19 tests on Wednesday. The project expects to run nearly 1,000 COVID-19 a day, giving Oregon a much-needed boost in its efforts to track the virus. Right now, Oregon tests between 7,000 and 8,000 people a week, Brown said.

Oregons lack of adequate testing infrastructure has dogged the states efforts to contain the virus. State public health officials repeatedly have said the state needs more tests to halt the spread, something that Brown repeated at a news conference on Tuesday."We need to ramp up testing in every region of the state," she said.

Yet state officials did not pursue a homegrown opportunity that taps the expertise of an Oregon university research laboratory.

From the start, testing has lagged in Oregon. Initial kits from the Centers for Disease Control and Prevention were faulty, and there was a lack of supplies. The state expected all tests to be conducted at the public health lab in Hillsboro but has since allowed testing by five hospital systems, two private labs and the University of Washington. Still, the state only has results for about 30,000 people, according to an Oregon Health Authority report on Monday.

The OSU project shines a light on the difficulties faced by entities outside the public health system to help Oregon track and quell the epidemic. The Oregon Health Authority apparently failed to recognize the contribution a veterinary lab could make despite examples in other states.

University veterinary labs in at least two other states Colorado and Oklahoma have been conducting COVID-19 testing for weeks. Each can process hundreds of tests a day. Their veterinary labs unlike OSUs had help from public authorities.

Physicians lack drugs to fight the virus, and it will be a year or more before a vaccine is on the market. The only tool public health officials have right now are tests.

"Testing is an essential pillar of any public health response to a disease outbreak, Dr. Sharon Meieran, a Multnomah County commissioner and emergency room doctor, told The Lund Report in an email. It allows for case identification, contact tracing and importantly, especially in congregate settings, the ability to isolate individuals who are infected so that they do not risk infecting others. Any increase in our capacity to test for COVID-19 will aid in our ability to respond to this disease at both an individual and community level."

Experts say that the more entities that test and the quicker the results, the sooner people will isolate themselves and stop spreading the highly contagious virus.

The lack of testing from the beginning has been one of the leading causes for where we are now," said Chunhuei Chi, director of OSUs Center for Global Health.

Lab Has Diagnostic Track Record

In Oregon, the idea to get the veterinary lab involved came from the medical community in Corvallis, including Good Samaritan Regional Medical Center. Frustrated over long waits for testing results, physicians approached the Oregon Veterinary Diagnostic Laboratory at OSU last month to see if officials there could use their equipment to run COVID-19 tests. The lab was a prime candidate to help.

Any additional testing capacity that they can provide would be welcomed by the region and the state of Oregon, said Dr. Adam Brady, an infectious disease specialist and chairman of the hospitals coronavirus task force, in an email.

The lab, part of the universitys Carlson College of Veterinary Medicine, has a long history of tracking illness, like viruses in sheep and hoof and mouth disease in cattle. It works with state epidemiologists and is part of a U.S. Food and Drug Administration network of about 45 facilities nationwide that specialize in investigating animal diseases. They analyze animal blood, urine, stool and tissue samples for signs of illnesses to help the federal agency investigate complaints about tainted food and drugs.

One of the labs machines extracts genetic material from samples, usually collected via nasal swabs. The other machine analyzes the genetic material and provides the results.

This is just the sort of technology needed to conduct COVID-19 tests.

Mark Ackermann, director of the veterinary lab, wanted to help out but to run human analyses, a lab needs to be certified by the Centers for Medicare & Medicaid Services. His lab lacked that certification.

To obtain it, a lab has to meet federal standards. That process is complicated and takes time, even for a research lab that already meets other federal standards to track diseases in animals.

So Ackermann asked the Oregon Health Authority for help in smoothing the way for the veterinary lab to conduct tests on its own or work with another facility.

Agency officials visited the lab and discussed federal certification requirements, said Jonathan Modie, a spokesman for the agency. But they didnt help. Theysuggested that Ackermann contact clinical laboratories instead.

Early on, Ackermann received support from Sen. Sara Gelser, D-Corvallis, who saw the potential in the idea. On March 26, Gelser tried to enlist the support of Gov. Kate Brown by emailing Browns chief of staff, Nik Blosser, and copying other lawmakers. That email, obtained by The Lund Report, encouraged the governors office to consider an executive order allowing COVID-19 tests at research universities. Gelser pointed out that Oklahomas governor had issued such an order enabling a university veterinary lab there to participate in testing.

Would the governor consider a similar executive order so that OSU could make the same application and hopefully come online immediately, Gelser wrote, calling it a game-changer for containment efforts.

Charles Boyle, a spokesman for Brown, said the office passed along the request to the health authority. He referred a reporter to the health authority for further comment.

Ackermann said he never heard from the governors office.

Partnership Is Formed

But the lab found a way forward on its own.

At the same time that Ackermann was crashing into a regulatory wall, another lab in Corvallis was trying to conduct testing. WVT Laboratory, a commercial lab that normally analyzes toxins in urine and runs drug tests, contacted Benton Countys emergency operations center to see what it needed to do to conductCOVID-19 testing. That contact led to WVT hooking up with OSU through Dr. Bruce Thomson, a retired family physician in Corvallis who does consulting work for the county.

The two labs complemented each other.

WVT Laboratory has the necessary certification from CMS to conduct COVID-19 testing. It also has an approved records system that meets federal privacy regulations for patients. And the veterinary lab has the equipment that WVT needed to run the tests.

Less than a week after they met on April 1, the heads of the two labs decided that OSU would contribute its equipment. The university lab will extract the genetic material from tests and WVT will run the tests. After contacting the county, the pact came together quickly, said Manny Cruz, chief executive officer of WVT, which has a staff of eight people.

In an interview, Thomson gave the Oregon Health Authority credit for visiting Corvallis even though that didnt lead to anything.

I know they were pretty darn busy juggling a lot of things and felt that they just couldnt be of any help to us, Thomson said.

But in an April 4 email to Ackermann and Sen. Brian Boquist, R-Dallas, Thomson criticized the agency.

Our pursuit was not supported in any way by OHA, Thomson wrote. In spite of all the obstacles that OHA enumerated several times during an hour-long pitch by us, it now appears that the lab instrument will be up and running.

The two labs trained together for the first time Friday, with a plan to ramp up testing this week. The lab will not collect samples directly from patients. Instead, local doctors will determine who needs testing, collect samples from patients and send them to the lab for testing.Similar Efforts Elsewhere

The public-private collaboration between OSU and WVT may be unique in the U.S. Other veterinary labs involved in COVID-19 testing have official support. Those states found ways to either obtain the federal certification for the veterinary lab or they hooked the lab up with a partner with federal approval.

Last month, the diagnostic veterinary lab at Colorado State University in Fort Collins forged the path by gaining federal certification through a collaboration with the universitys student health center lab.

Kristy Pabilonia, director of the veterinary lab at Colorado State, said the student health centers lab director had the right qualifications, enabling the veterinary lab to apply for the certification, which requires audits and inspections. Usually, the federal government completes a background check and vets the director. The Colorado lab didnt need that step because the student lab director was already qualified.

The veterinary lab equipment can handle 200 tests a day.

Oklahoma State University is also running COVID-19 tests. It has five machines processing 1,000 tests a day at its diagnostic laboratory, which usually investigates animal diseases and outbreaks. The university could expand to around-the-clock testing if necessary, said Kenneth Sewell, the universitys vice president of research.

Like OSU, the veterinary lab at Oklahoma State lacked CMS certification. But it teamed up with its medical school, which is run by a certified director. The medical schools certification allows the lab to run tests.

The states governor, Kevin Stitt, also helped by signing an executive order that allowed the university to do the tests.

We became an extension or arm of the public health process so the hospitals and health care providers and pop-up specimen collection centers could send specimens to us, Sewell said. It allowed us to relieve the pressure on the department of health.

The Oregon solution came together differently. Ackermann, who avoided criticizing the health authority, said he was grateful that WVT was eager to collaborate.

They were willing to help, so lets go down that road and see where it takes us.

This story is published as part of a collaborative of news organizations across Oregon sharing stories in the public interest. Salem Reporter is part of the collaborative.

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Without state's help, OSU lab found its own way to help COVID-19 testing - Salem Reporter

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