Fact check: Were elderly Italians left to die? And is socialized health care to blame? – USA TODAY

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The Associated Press visited a new intensive care ward in Brescia, one of the hardest-hit provinces in Lombardy. Dr. Sergio Cattaneo, the hospitals head of anesthesiology and intensive care, says hes seen many changes to fight the pandemic. (March 18) AP Domestic

Various claims thatItalians over the age of 80 would be "left to die" have surfaced within the past week on social media, with some posts saying the blame falls on Italy's socialized health care system.

Italy's COVID-19 fatality rate of 5% is higher than the global average of 3.5%. As the country's confirmed cases continue to surge, health officials are scrambling to find adequate resources.

Despite a countrywide lockdown,Italy reached a grave milestone this week when the country's death tollsurpassed China's as of March 19,3,405 people have died.

Italy has an older population,with a median age of 47.3, compared to 38.3 in the United States. Older populations are much more susceptible to complications from COVID-19, and many of the reported deaths in Italy have been people in their 80s and 90s.

The claims of Italy abandoning its elderly population began to surface following a report in the Telegraph about a document prepared by a crisis management unit in Turin, a northern Italiancity hit hard by the virus.

A man wearing a mask rides a scooter in Milan, Italy, March 11, 2020. Italy is mulling even tighter restrictions on daily life and has announced billions in financial relief to cushion economic shocks from the coronavirus. (Photo: Luca Bruno, AP)

The document seen by the Telegraph is a guideline for if and when it"becomes impossible to provide all patients with intensive care service,according to the news outlet, which did not publish a copy of it.

If the crisis reaches a point where health careaccess is too strained and needs to be limited, the document lays out plans for how to prioritize patients.

According to the Telegraph, the document's criteria for intensive therapy in emergency cases includes an age of less than 80 or a score of less than five on the Charlson Comorbidity Index, which indicates a patient's other medical conditions and mortality.

Luigi Icardi, a councilor for health in Piedmont, told the Telegraph that he never wantedthe crisis to reach this point, but that the document "will be binding and will establish, in the event of saturation of the wards, a precedence code for access to intensive care,based on certain parameters such as potential survival."

Italy surpasses China in deaths.(Photo: USA TODAY)

Despite the tentative guidelines in the document, it is not true that Italy as a whole has decided not to treat their elderly for the coronavirus.

The truth is, instead, that overwhelmed Italian health officials are planning for the worst, given the recent influx of cases and lack of available resources. If cases continue to surge, officials might be forced to prioritize care for those with "the best chance of success" and the "best hope of life."

The second part of theclaim that stemmed from the Telegraphreport blamed Italy's socialized health care for the lack of available resources and went viral on Facebook.

One person who posted that claim and saw it go viral, Gene Ballinger,did not respond to request for comment.

Throughout the pandemic, Italy's Prime Minister Giuseppe Contehas remained consistent on his health care promises for all Italians.

"We live in a system in which we guarantee health and the right of everyone to be cured. It's a foundation, a pillar, and I'd say a characteristic of our system of civilization," Conte said in a public statement on March 9. "And thus, we can't allow ourselves to let our guard down."

Health care officials in China were faced with a similar dilemma when the number of cases surpassed the capability of the existing treatment options. As hospitals in China became overwhelmed, patients were forced to wait extended periods of time for treatment.

In the U.S., health care is not socialized.But officials across the country are preparing to facethe same dilemma seen in Italy as cases continue to multiply and available resources deplete.

A new Harvard analysis reveals thathospitals throughout the United States will not have enough beds for patients if the virus continues to spread and capacity is not adequately expanded.

According to the analysis, in 40% of marketsaround the country, hospitals will not be able to make enough room for all patients who fall ill from the coronavirus.

Medical staff work at one of the emergency structures that were set up to ease procedures at the Brescia hospital in northern Italy, March 16, 2020.(Photo: Luca Bruno, AP)

This statistic reflects a "moderate" scenario by the analysis team's standards andassumes 40% of adults will become infected with the virus over the next 12 months.

These numbers are not exact and do not take into account various efforts from hospitals across the country including sending home patients with less critical conditions.

The global push for social distancing, self-isolation and self-quarantine is a preemptive effort to prevent overwhelming health care systems.

The longer the disease takes to spread, the more time hospitals have to accommodate patients. In the United States, officials are attempting to "flatten the curve" and not overwhelm the health care system by closing businesses and schools and canceling large events.

Blaming Italy's socialized health care system for the lack of availableresources doesn't hold up because nonsocialized health care systems, such as those in the United States, are facing similarshortages.

While some Italian health officials are planning for the worst, the health care prioritizationguidelines have not yet been implemented and are influenced bymultiple factors including age, preexisting conditions and available resources. As forthe second claim about socialized health care,Italy's system has become overwhelmed due to the sheer amount of cases and patients, not because of its design. We rate these claims as "false," based on our research.

However, should Italy implement its protocol that triages patients based on age and other conditions, we would change the rating of these claims to "partly false."

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Fact check: Were elderly Italians left to die? And is socialized health care to blame? - USA TODAY

Akouos Announces New Data at the Association for Research in Otolaryngology Midwinter Meeting – Business Wire

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BOSTON--(BUSINESS WIRE)--Akouos, a precision genetic medicine company developing gene therapies to potentially improve and preserve hearing, announced today that data from its inner ear gene therapy platform will be presented during the 43rd Annual Midwinter Meeting of the Association for Research in Otolaryngology (ARO), being held January 25 to January 29, 2020 in San Jose, CA.

Akouos continues to advance our platform for inner ear disorders, and we are excited to share our progress with the scientific community, said Greg Robinson, Ph.D., chief scientific officer of Akouos. The data presented at ARO further substantiates Akouoss use of AAVAnc80 vector technology and its potential to address many forms of hearing loss.

SYMPOSIUM

Title: The Adeno-associated Viral Anc80 (AAVAnc80) Vector - Precision Genetic Medicines to Address Hearing LossPresenter: Michelle Valero, Ph.D., Director, Anatomy & Physiology, AkouosSession: Symposium 11Date and Time: Saturday, January 25, 3 p.m. (PST)

POSTER PRESENTATIONS

Title: The Adeno-associated Viral Anc80 Vector Efficiently Transduces Inner Ear Cells in Olive Baboons (Papio anubis)Day and Time: Monday, January 27, 1 p.m. (PST)

Title: The Adeno-associated Viral Anc80 Vector Efficiently Transduces Inner Ear Cells in Cynomolgus Macaques (Macaca fascicularis)Day and Time: Monday, January 27, 1 p.m. (PST)

Title: Dual Adeno-associated Viral Anc80 Vector Efficiently Transduces Inner Ear Cells in Non-human PrimatesDay and Time: Monday, January 27, 1 p.m. (PST)

About Akouos

Akouos is a precision genetic medicine company dedicated to developing gene therapies with the potential to improve and preserve hearing. Leveraging its adeno-associated viral (AAV) vector-based gene therapy platform, Akouos is focused on developing precision therapies for forms of sensorineural hearing loss. Headquartered in Boston, the Company was founded in 2016 by world leaders in the fields of neurotology, genetics, inner ear drug delivery, and AAV gene therapy. Akouos has strategic partnerships with Massachusetts Eye and Ear and Lonza, Inc. For more information, please visit http://www.akouos.com.

About AAVAnc Technology

Ancestral AAV (AAVAnc) technology was developed in the laboratory of Luk Vandenberghe, Ph.D., Director of the Grousbeck Gene Therapy Center at Harvard Medical School. AAVAnc technology uses computational and evolutionary methods to predict novel conformations of the adeno-associated viral particle. AAVAnc80, one of 40,000 AAVAnc vectors, has demonstrated preliminary safety and effective gene delivery in both mice and non-human primates in numerous preclinical studies.

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Akouos Announces New Data at the Association for Research in Otolaryngology Midwinter Meeting - Business Wire

How one woman became the exception to her familys Alzheimers history – Science News

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A cruel twist of genetic fate brought Alzheimers disease to a sprawling Colombian family. But thanks to a second twist, one member of the clan, a woman, managed to evade the symptoms for decades. Her escape may hold the key to halting, or even preventing, Alzheimers.

The inherited version of Alzheimers disease erodes peoples memories early, starting around age 40. In this family and others, a mutation in a gene called presenilin 1 eventually leaves its carriers profoundly confused and unable to care for themselves. Locals around the Colombian city of Medelln have a name for the condition: la bobera, or the foolishness.

The woman in the afflicted family who somehow fended off the disease carried the same mutation that usually guarantees dementia. And her brain was filled with plaques formed by a sticky protein called amyloid. Many scientists view that accumulation as one of the earliest signs of the disease. Yet she stayed sharp until her 70s.

Researchers were stumped, until they discovered that the woman also carried another, extremely rare genetic mutation that seemed to be protecting her from the effects of the first one. This second mutation, in a different Alzheimers-related gene called APOE, seemed to slow the disease down by decades, says Joseph Arboleda-Velasquez, a cell biologist at Harvard Medical School.

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There was this idea of inevitability, he says. But the womans circumstances bring a different perspective one in which amyloid buildup no longer guarantees problems. Arboleda-Velasquez and colleagues reported the details of the womans exceptional case November 4 in Nature Medicine, omitting the womans name and precise age to protect her privacy.

Although the discovery is based on one person, it points to a biological weak spot in the degenerative disease that affects an estimated 5.8 million people in the United States alone. So far, nearly every clinical trial designed to slow or stop the disease has failed. Those heartbreaking disappointments have prompted scientists to expand their search for treatments.

Perhaps this unusually resilient woman in Colombia shows a way to halt the disease, or at least slow it down. Can we come up with a drug that does this to people who dont have a mutation? asks Arboleda-Velasquez. The potential for that is tremendous.

The vast majority of people with Alzheimers have a sporadic form of the disease with no clear genetic culprit. These people often reach their 70s or 80s before signs of dementia appear. Mutations that cause trouble much earlier, such as the Paisa mutation found in the Colombian family, are unusual. But despite their different origins and different timelines, these two versions of Alzheimers are thought to progress in somewhat similar ways.

Normally, presenilin 1 makes a protein that helps chop up the long, sticky amyloid precursor protein. One of the resulting small bits is called amyloid-beta. Those smaller pieces are harmlessly washed out of the brain. The mutated presenilin 1 gene found in the Colombian family, however, creates a kink in the chopping process that leads to an abundance of a version of amyloid that knits itself into plaques between brain cells.

This pileup is already visible in brain scans of people in their 20s who carry the mutation. By their mid-40s, many of these people have trouble remembering; they typically develop full-blown dementia by age 50.

Inheriting just one copy of the mutation is enough to lead to excess amyloid, and ultimately dementia. The mutations powerful effect in this family is one of the strongest arguments for the fact that amyloid plays a critical role in Alzheimers, says immunologist and aging expert Richard J. Hodes, director of the National Institute on Aging in Bethesda, Md. Since taking on the role in 1993, Hodes has helped set the course for U.S.-funded Alzheimers research, allocating support for promising projects, including studies happening in Colombia.

The Colombian family, 5,000 members strong, includes an estimated 1,000 or so people who carry the Paisa mutation in the presenilin 1 gene. Their involvement in the research has been invaluable. Access to hundreds of people known to be at high risk for the disease allows scientists to study how Alzheimers unfolds, particularly at its earliest stages, and has led to reports of early signs of Alzheimers, both in the brain and the blood. Family members have gone to great lengths to help, walking or taking a bicycle to the nearest bus stop, and then taking a bus to a train, for many hours, to come to the clinic, Hodes says.

During Hodes recent visit to the Medelln area, a resident told him how the disease is just a part of their lives: If I have the disease, I know that my family, my brother and my sister, will take care of me. And if I dont, I will take care of them.

When Colombian researchers learned of the woman who stayed sharp until her 70s, they arranged for her to travel to Boston in the summer of 2016, accompanied by family members and a research assistant. There, neuroimaging researcher Yakeel T. Quiroz and her colleagues used brain scans to measure levels of amyloid and other markers of brain health, including another Alzheimers-related protein called tau, which can tangle up inside nerve cells.

Those scans revealed a brain loaded with amyloid, says Quiroz, of Harvard Medical School. This woman had most likely been accumulating amyloid for decades. On a scale commonly used to quantify amyloid in the brain, she scored 1.96, well above the threshold of 1.2 that signifies extensive amyloid buildup. Her score was, pretty much the highest that we have seen in anybody we have scanned so far, Quiroz says.

Genetic analyses revealed that the woman had whats called the Christchurch mutation in both copies of her APOE gene. Further tests suggested that this mutation, named for the New Zealand city where it was first found, was shielding her from the disease. The fact that the woman had huge amounts of amyloid in her brain, yet didnt seem impaired until her 70s, is extremely surprising, interesting, provocative and potentially very, very informative, Hodes says.

Scientists need to do more work to confirm that the APOE Christchurch mutation protected her brain. Still, the results reveal a simple truth, Hodes says. Amyloid itself is not necessarily sufficient to cause dementia.

Studies outside of the Colombian family also make clear that amyloid isnt the whole story. Other cellular actors contribute to the death of nerve cells and memory loss that Alzheimers brings. Nerve cellclogging tangles of tau and other signs of brain illness are tightly linked to brain decline, research from many studies has shown. Thats reflected in observations from a study of 480 people age 60 and older who live around Rochester, Minn.

These people, none of whom showed signs of dementia, were randomly chosen to be invited into the study, an unbiased selection that offered researchers a glimpse of brain health in the wider population.

To find out which brain changes best predict future memory loss, neuroradiologist Clifford R. Jack Jr. of the Mayo Clinic in Rochester and colleagues tested volunteers memory performance while measuring their amyloid levels and other brain signals. Amyloid seemed to be closely involved in memory decline over about five years but only in the right context, the team reported in June 2019 in JAMA.

Without either of two other troublesome markers tau tangles or brain shrinkage amyloid didnt predict memory loss. In other words, amyloid might be setting up the shot, but then it passes the ball.

Amyloid in the head is the first stage of what will ultimately lead to full-blown Alzheimers disease, Jack says. But there can be a lot of time between that early stage of amyloid accumulation and the development of symptoms.

Among the Colombian family members, that interval lasts around 10 to 15 years. The same is roughly true for people with the sporadic form of Alzheimers. But for the woman described in the report in Nature Medicine, that lag seemed twice as long.

That suggests that at least its possible to live with amyloid not just for 15 years, but for many decades, says Paul Aisen, director of the University of Southern Californias Alzheimers Therapeutic Research Institute in San Diego. Living healthy longer: Thats very exciting.

The protective effect of the womans mutation seems to come from an extremely specific change. In the Christchurch variant, a single spot in the APOE gene is tweaked. The resulting protein has a serine amino acid swapped in for the standard arginine.

The swap prevents the APOE protein from binding to some sugar-dotted proteins called heparan sulfate proteoglycans, or HSPGs, experiments on the isolated proteins revealed. Earlier studies showed that HSPGs may promote amyloid accumulation and nudge nerve cells to slurp up more toxic tau.

But to misbehave, HSPGs might need to partner with the APOE protein. The Christchurch mutation could have protected the womans brain by scrambling that nefarious relationship, the researchers suspect. Without that specific connection between APOE and HSPGs, the disease process gets stalled, Arboleda-Velasquez says. This really puts a block on the cascade of events.

Fleshing out the APOE proteins normal biological cascade, and how that changes with the Christchurch mutation, is going to allow for much more finely targeted drug development, says Aisen, who also works as a consultant for Biogen, a biotechnology company in Cambridge, Mass. The company is developing an amyloid-targeting drug called aducanumab and is expected to apply for approval from the U.S. Food and Drug Administration this year (SN: 1/18/20, p. 8).

As one of the strongest genetic risk factors for dementia, the APOE gene has long been scrutinized as a possible target for Alzheimers drugs. People who carry a version of the gene called APOE4 have a higher risk of Alzheimers.

The APOE2 version dramatically lowers the risk, Quiroz, Arboleda-Velasquez and colleagues report in preliminary research posted online November 2 at medRxiv.org. APOE3 usually brings an average risk of Alzheimers, with the notable exception of the version with the Christchurch mutation carried by the Colombian woman.

In the general population, old age is the biggest risk factor for Alzheimers. As the number of older people balloons, so too will the number of people with dementia. By 2050, an estimated 13.8 million people in the United States will have Alzheimers. Worldwide, an estimated 50 million people have dementia; Alzheimers accounts for the bulk of those cases.

The family in Colombia continues to help. A clinical trial testing a drug that is designed to lower amyloid is under way in Colombia. People who have the Paisa mutation but have not shown Alzheimers symptoms, as well as people without the mutation, are receiving the drug. The drug, crenezumab, is an antibody thats thought to mark amyloid for destruction by immune cells. Its being developed by Roche/Genentech.

Quiroz and her colleagues also plan to follow the Colombian woman and other members of the family over time, as part of a research exchange between Fundacin Universidad de Antioquia in Medelln, which has led the studies on this family, and Massachusetts General Hospital in Boston.

Each month, the project, called COLBOS, for Colombia-Boston, flies a new group of about five adult participants to Boston for extensive evaluation, including thinking and memory tests, brain scans and measurements of smelling ability, fitness and music perception. Participants being studied in Colombia are as young as 9 years old.

The project may yield insights about how Alzheimers takes hold early on. But in a way, the initial trigger might not even matter. It could be that the cause or more likely, causes of Alzheimers might ultimately be poor targets for drugs, Arboleda-Velasquez says.

People with loved ones suffering from Alzheimers, including the Colombian family, dont necessarily care what causes the disease, Quiroz says. They are more interested in seeing if there is anything that can help them to get better. Thats what the patients and families are waiting for.

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How one woman became the exception to her familys Alzheimers history - Science News

Escaping Alzheimer’s – University of California

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There is, in Colombia, a family with the tragic legacy of forgetfulness.

People in this large family get Alzheimers like clockwork at age 45-50, said UC Santa Barbara neuroscientist Kenneth S. Kosik, the campuss Harriman professor of Neuroscience and co-director of the Neuroscience Research Institute. Their aggressive, genetic form of the disease has been passed down from generation to generation, causing rapid cognitive and physical declines in both the men and the women of this family.

For decades, Kosik and colleagues, including Dr. Francisco Lopera of the University of Antioquia; Dr. Eric Reiman of the Banner Alzheimers Institute in Phoenix; clinical neuropsychologist Yakeel Quiroz of Massachusetts General Hospital; and Dr. Joseph Arboleda-Vasquez of Massachusetts Eye and Ear, have been studying this family, from their brains right down to their genes. They have even traced the specific gene mutation of this disease back as far as the time of the Spanish conquistadors.

During their studies the researchers also have witnessed the predictable onset of the disease as members of this family enter into their middle years. Sometimes it happens sooner, sometimes later, but all paths have always led to the same destination.

But one woman has defied the odds. Now in her late 70s, she has the mutant gene and the plaques of amyloid protein that are the hallmark of Alzheimers disease yet she has exhibited no signs of cognitive impairment associated with Alzheimers.

When you find an escapee, its extremely interesting, said Kosik, co-author of a study that appears in the journal Nature Medicine. The woman, and others who are considered outliers in the normal trend of neurodegeneration of this family, may present hints at a new approach for therapy for and even prevention of the disease, he said.

The culprit in this version of Alzheimers is a mutation to the presenilin 1 gene, called E280A, copies of which are found in every member of this family afflicted with the disease. It is implicated in the high production of those sticky amyloid plaques.

The mutation is known to cause the onset of the disease at age 45, and its really flagrant by the time youre in your 50s, Kosik said. The woman, in her late 60s at the time they were conducting their study, was positive for the mutation, but exhibited few symptoms.

It was amazing, Kosik said. In the course of their analysis they found that the woman also had another mutation in another gene that is responsible for making lipoproteins in the central nervous system, a gene called apolipoprotein E or APOE. A variant of this gene called the Christchurch variant is exceedingly rare, but its presence in the patient hinted at a protective mechanism. The researchers turned to the Kosik Labs extensive collection of genomes to look for other family members with this same variant.

They asked us especially to look at people who were also outliers who got it at a very late age, Kosik said. They found a few others who had the variant, he said. Importantly, however, while there were others who did carry the Christchurch mutation, they all carried one copy, inherited from one parent.

The key thing about this discovery is that this patient is homogyzous for the variant; it came from both the mother and the father, Kosik explained. The researchers lab studies showed that the APOE gene variant might delay the onset of Alzheimers by binding to sugars (called heparin sulphate proteoglycans, or HSPG) and preventing the uptake and inclusion of tau proteins in neurons that ultimately lead to the tangles that are a pathological hallmark of the disease. Tau is a common structural protein in the brains of patients with Alzheimers and other neurodegenerative diseases that becomes sticky and insoluble.

More work needs to be done to investigate this single patients resistance to a disease that affects her extended family of 6,000 people, but this promising development could point toward an approach and a therapy for the estimated 44 million people in the world who have Alzheimers, a number that continues to rise.

"This finding suggests that artificially modulating the binding of APOE to HSPG could have potential benefits for the treatment of Alzheimer's disease, even in the context of high levels of amyloid pathology," said the papers co-lead author Joseph F. Arboleda-Velasquez, in a press statement.

For Kosiks part, he and Arboleda-Vasquez (who formerly was Kosiks graduate student at Harvard) continue to probe for other genetic one-offs and outliers that may contribute to Alzheimers resistance.

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Escaping Alzheimer's - University of California

Blackstone to invest $400 million in gene therapy venture with Ferring – Reuters

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(Reuters) - Blackstone Group Inc (BX.N) said on Monday it will invest $400 million in a joint venture with Swiss drug company Ferring that is working on an experimental gene therapy for bladder cancer, the private equity giants largest ever bet on drug development.

FILE PHOTO: The ticker and trading information for Blackstone Group is displayed at the post where it is traded on the floor of the New York Stock Exchange (NYSE) April 4, 2016. REUTERS/Brendan McDermid

Investing in yet-to-be-approved medicines is a lucrative but also risky proposition for buyout firms, and only few have had the stomach to place such bets. Blackstone made its foray in the sector last year, acquiring Clarus, an investment firm specializing in life sciences.

For its part, Ferring will invest $170 million in the joint venture with Blackstone, dubbed FerGene, bringing its total funding to $570 million, the companies said in a statement.

FerGene is developing a gene therapy for bladder cancer patients with an aggressive form of the disease whose current options include having their bladder removed. The treatment works by entering the walls of the bladder where it releases a gene to trigger the patients own body to make a protein to fight off cancer.

We believe, and Ferring also believes, that this can change the standard of care in bladder cancer, a terrible disease, Nicholas Galakatos, senior managing director of Blackstone Life Sciences, said in an interview.

Oncology is a new area for Ferring, but it is one that we as Blackstone Life Sciences have a lot of experience in

The team assembled by Blackstone has worked at several of the worlds largest cancer drugmakers, including Roche unit Genentech, Merck & Co Inc (MRK.N), and Millennium Pharmaceuticals, now a part of Takeda Pharmaceutical Co Ltd (4502.T).

To minimize its risk, Blackstone invests in the late stages of drug development, when a medicine has already gone through important milestones. Late-stage drug development can also be expensive because of the clinical trials involved, something that Blackstone is seeking to capitalize on by partnering with pharmaceutical firms looking to share the cost burden.

FerGenes therapy, named nadofaragene firadenovec, is currently in the final stage of clinical research, results from which will be presented on Dec. 5 at the Society of Urologic Oncologys annual meeting.

Since it launched its life sciences unit, Blackstone has also formed a new company with Novartis AG (NOVN.S) to study a type of heart drug. Blackstone invested $250 million in that venture.

Reporting by Rebecca Spalding in New York; Editing by Alistair Bell

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Blackstone to invest $400 million in gene therapy venture with Ferring - Reuters

Study Shows Evolution Turns Genes Back On to Regain Function – Stony Brook News

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STONY BROOK, NY, November 25, 2019 Genes often mutate and lose their natural or synthetic function over long-term evolution, which could be good if that stops drug resistance of infectious microbes or cancer. A new study by Stony Brook University researchers, published online in PNAS, shows that evolution can exploit positive feedback (PF) within cells to restore gene function. Such repair by evolution may provide a basis for regaining lost gene function, which has implications in medicine and other scientific endeavors.

Based on the idea and experiments of an undergraduate Biomedical Engineering student, Mirna Kheir, and led by Gbor Balzsi, PhD, the Henry Laufer Associate Professor in Stony Brook Universitys Laufer Center for Physical and Quantitative Biology, and Department of Biomedical Engineering, the study included using synthetic PF in yeast cells by way of a chromosomally integrated gene circuit to test the process of regaining lost gene functions.

We showed through these experiments and computational models that many drugs can activate mutant resistance genes through this process, explains Balzsi. Essentially we exposed mutant, drug-sensitive cell populations to conditions where regaining resistance would be beneficial, and we found adaptation scenarios with or without repairing lost gene circuit function.

The results also suggest that inactive, nonfunctional natural drug resistance modules can also regain function upon drug treatment, quickly converting drug-sensitive cancer cells or microbes in drug-resistant ones.

The research is supported in part by a National Institutes of Health (NIH) National Institute of General Medical Sciences grant (R35 GM122561), the Laufer Center, and a Swiss National Science Foundation Ambizione grant.

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About Stony Brook UniversityStony Brook University, widely regarded as a SUNY flagship, is going beyond the expectations of what todays public universities can accomplish. Since its founding in 1957, this young university has grown to become one of only four University Center campuses in the State University of New York (SUNY) system with over 26,000 students, more than 2,700 faculty members and 18 NCAA Division I athletic programs. Our faculty have earned numerous prestigious awards, including the Nobel Prize, Pulitzer Prize, Indianapolis Prize for animal conservation, Abel Prize and the inaugural Breakthrough Prize in Mathematics. The University offers students an elite education with an outstanding return on investment: U.S.News & World Report ranks Stony Brook among the top 40 public universities in the nation. Its membership in the Association of American Universities (AAU) places Stony Brook among the top 62 research institutions in North America. As part of the management team of Brookhaven National Laboratory, the University joins a prestigious group of universities that have a role in running federal R&D labs. Stony Brook University fuels Long islands economic growth. Its impact on the Long island economy amounts to $7.38 billion in increased output. Our state, country and world demand ambitious ideas, imaginative solutions and exceptional leadership to forge a better future for all. The students, alumni, researchers and faculty of Stony Brook University are prepared to meet this challenge.

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Will patients’ lifestyles become more important to precision medicine than gene sequencing? – Genetic Literacy Project

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While much of the excitement surrounding precision medicine focuses on using genomics to tailor personalized treatment plans, speakers at the Precision Medicine Summit said theres more to it.

We cannot achieve precision medicine without having everyone be a participant and benefit and understand, said India Barnard-Hook, director of strategy and associate director of precision medicine at University of California, San Francisco. Precision medicine is about much more than genomics.

Social determinants of health, for instance, typically occur outside the healthcare system and have a significant impact on both health and individual outcomes.

You have to know a lot more than the clinical phenotype, said Linda Chin, chief innovation officer for health affairs at The University of Texas Health System.If you understand all the other factors that contribute to diseases, those can alter the course of the disease and ultimately prevent it.

Penn Medicine associate vice president of health technology and academic computing Brian Wells even made the bold prediction that genetic sequencing may become less relevant as cancer treatments become increasingly sophisticated.

If we discover one immunotherapy that applies to all cancers, we really dont need to sequence your genome anymore, Wells said. Were at a tipping point and sequencing could become less important.

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post:With precision medicine, social determinants could be more insightful than genetics

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Will patients' lifestyles become more important to precision medicine than gene sequencing? - Genetic Literacy Project

Childhood Cancer Radiation May Cause Unwanted Gene Mutation in Some – Sioux City Journal

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FRIDAY, Aug. 4, 2017 (HealthDay News) -- Some adult survivors of childhood cancer go on to develop brain tumors, and now researchers say they've found a gene mutation that seems to increase that risk.

The researchers said their findings could lead to ways to prevent these brain tumors.

Adults who had radiation to their head and spine to treat childhood cancer have a greater risk of meningiomas. These tumors, which are often benign, are the most common type of brain tumor in adults, according to the American Brain Tumor Association.

In this study, Canadian researchers looked at 31 radiation-induced meningiomas in patients who underwent head and spine radiation during childhood. Most of them (74 percent) had survived either leukemia or pediatric brain cancer.

These brain tumors were compared with 30 meningiomas among people in the general population.

Gelareh Zadeh, the study's co-principal investigator, said that radiation-induced meningiomas appear to be the same as those that just occur sporadically. They look the same on MRI scans and under a microscope. And, they feel the same during surgery, Zadeh said.

"What's different is [that radiation-induced tumors] are more aggressive, tend to recur in multiples and invade the brain, causing significant morbidity and limitations (or impairments) for individuals who survive following childhood radiation," Zadeh said.

Zadeh is a brain tumor researcher and associate professor in the neurology division at the University of Toronto.

Ken Aldape is a co-principal investigator on the study. He said the research team found a specific rearrangement involving the NF2 gene in radiation-induced meningiomas. He said there are likely other genetic rearrangements caused by radiation-induced DNA damage.

"So one of the next steps is to identify what the radiation is doing to the DNA of the meninges," Aldape said in a University Health Network news release. Aldape is a professor of laboratory medicine and pathobiology at the University of Toronto.

Figuring out which group of childhood cancer patients have the highest risk of these radiation-induced tumors is critical. These patients could be followed closely for early detection and management, Aldape explained.

The study was published online Aug. 4 in the journal Nature Communications.

The American Brain Tumor Association has more on meningiomas.

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Childhood Cancer Radiation May Cause Unwanted Gene Mutation in Some - Sioux City Journal

Veracyte Announces New Data That Advance Understanding of Genomic Alterations Targeted by Precision Medicine Therapies for Thyroid Cancer – Business…

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SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Veracyte, Inc. (Nasdaq: VCYT) today announced new data that advance understanding of the frequency, positive predictive value and co-occurrence of genomic alterations that are targeted by newly available and investigational precision medicine therapies for thyroid cancer. The findings were enabled by Afirma Xpression Atlas analyses, which uses RNA sequencing, of Veracytes extensive biorepository of thyroid nodule fine needle aspiration (FNA) samples from patients undergoing evaluation for thyroid cancer. The data were presented this week during the 89th Annual Meeting of the American Thyroid Association (ATA).

In one study, researchers assessed the frequency of ALK, BRAF, NTRK and RET fusions in nearly 48,000 consecutive patients whose thyroid nodule FNA samples were deemed indeterminate, suspicious for malignancy or malignant (Bethesda III/IV, V and VI categories, respectively) by cytopathology. The researchers found that 425 (0.89 percent) of the FNA samples harbored one of the alterations, with NTRK fusions the most common at 0.38 percent, followed by RET (0.32 percent), BRAF (0.13 percent) and ALK (0.06 percent). Additionally, RNA whole transcriptome sequencing demonstrated differences in the prevalence of these four fusions across Bethesda categories, with Bethesda V being the highest.

NTRK fusion inhibitors have received pan-cancer FDA approval and clinical trials have included selective inhibitors of ALK, BRAF, NTRK and RET, which makes their detection in patients with thyroid cancer of interest to physicians, said Mimi I. Hu, M.D., professor at The University of Texas MD Anderson Cancer Center, who presented the findings in a poster. As our understanding of the role of genomics in thyroid cancer advances, this information offers the potential to optimize initial treatment, predict response to treatment and prioritize selective targeted therapy should systemic treatment be needed.

In another study, researchers evaluated the positive predictive value of the NTRK, RET, BRAF and ALK fusions in 58 patients with indeterminate thyroid nodules (Bethesda III/IV categories) from Veracytes biorepository for whom surgical pathology diagnoses were available. They found that NTRK and RET fusions were associated with malignancy in 28 of 30 nodules, while risk of malignancy was lower among nodules with ALK (67 percent) or BRAF (75 percent). In a third study, researchers found that when using RNA sequencing data on a large sample of nearly 48,000 thyroid nodule FNA samples (Bethesda categories III-VI), they identified 263 co-occurrences of gene fusions and variants that were previously considered mutually exclusive.

The findings from these three studies underscore the power of our extensive biorepository of thyroid nodule FNA samples and our optimized RNA sequencing platform to advance understanding of the genomic underpinnings of thyroid cancer and to better capture the biology of thyroid lesions, said Richard T. Kloos, M.D., senior medical director, endocrinology, at Veracyte. As precision medicine therapies that target specific gene alterations emerge, understanding individual patients genomic profiles becomes increasingly important to physicians. Our Afirma Xpression Atlas provides this information at the same time as initial diagnosis with the Afirma Genomic Sequencing Classifier, or GSC, to help inform treatment decisions.

Also during the ATA meeting, Veracyte unveiled its new Afirma patient report, which in addition to identifying patients with benign or suspicious-for-cancer nodules among those deemed indeterminate by cytopathology, based on Afirma GSC results, now provides individualized and actionable variant and fusion information on each patient. This information includes: risk of malignancy, associated neoplasm type, relative risk of lymph node metastasis and extrathyroidal extension; availability of FDA-approved therapy; and genetic counseling and germline testing considerations. This information is also provided for patients with cytopathology results that are suspicious for malignancy or malignant (Bethesda V and VI).

About Afirma

The Afirma Genomic Sequencing Classifier (GSC) and Xpression Atlas provide physicians with a comprehensive solution for a complex landscape in thyroid nodule diagnosis. The Afirma GSC was developed with RNA whole-transcriptome sequencing and machine learning and helps identify patients with benign thyroid nodules among those with indeterminate cytopathology results in order to help patients avoid unnecessary diagnostic thyroid surgery. The Afirma Xpression Atlas provides physicians with genomic alteration content from the same fine needle aspiration samples that are used in Afirma GSC testing and may help physicians decide with greater confidence on the surgical or therapeutic pathway for their patients. The Afirma Xpression Atlas includes 761 DNA variants and 130 RNA fusion partners in over 500 genes that are associated with thyroid cancer.

About Veracyte

Veracyte (Nasdaq: VCYT) is a leading genomic diagnostics company that improves patient care by providing answers to clinical questions that inform diagnosis and treatment decisions without the need for costly, risky surgeries that are often unnecessary. The company's products uniquely combine RNA whole-transcriptome sequencing and machine learning to deliver results that give patients and physicians a clear path forward. Since its founding in 2008, Veracyte has commercialized seven genomic tests and is transforming the diagnosis of thyroid cancer, lung cancer and idiopathic pulmonary fibrosis. Veracyte is based in South San Francisco, California. For more information, please visit http://www.veracyte.com and follow the company on Twitter (@veracyte).

Cautionary Note Regarding Forward-Looking Statements

This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as: "anticipate," "intend," "plan," "expect," "believe," "should," "may," "will" and similar references to future periods. Examples of forward-looking statements include, among others, the ability of Veracytes Afirma Xpression Atlas to analyze FNA samples to help diagnose thyroid cancer, the expected impacts of Veracytes collaboration with Johnson & Johnson in developing interventions for lung cancer, on Veracytes financial and operating results, on the timing of the commercialization of the Percepta classifier, and on the size of Veracytes addressable market. Forward-looking statements are neither historical facts nor assurances of future performance, but are based only on our current beliefs, expectations and assumptions. These statements involve risks and uncertainties, which could cause actual results to differ materially from our predictions, and include, but are not limited to: our ability to achieve milestones under the collaboration agreement with Johnson & Johnson; our ability to achieve and maintain Medicare coverage for our tests; the benefits of our tests and the applicability of clinical results to actual outcomes; the laws and regulations applicable to our business, including potential regulation by the Food and Drug Administration or other regulatory bodies; our ability to successfully achieve and maintain adoption of and reimbursement for our products; the amount by which use of our products are able to reduce invasive procedures and misdiagnosis, and reduce healthcare costs; the occurrence and outcomes of clinical studies; and other risks set forth in our filings with the Securities and Exchange Commission, including the risks set forth in our quarterly report on Form 10-Q for the quarter ended September 30, 2019. These forward-looking statements speak only as of the date hereof and Veracyte specifically disclaims any obligation to update these forward-looking statements or reasons why actual results might differ, whether as a result of new information, future events or otherwise, except as required by law.

Veracyte, Afirma, Percepta, Envisia and the Veracyte logo are trademarks of Veracyte, Inc.

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Veracyte Announces New Data That Advance Understanding of Genomic Alterations Targeted by Precision Medicine Therapies for Thyroid Cancer - Business...

Study: Meditation, Yoga and Related Practices Can ‘Reverse’ DNA Reactions – Sci-News.com

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According to a study published in the journal Frontiers in Immunology, mind-body interventions such as mindfulness, yoga, Tai Chi, Qigong, relaxation response, and breath regulation dont simply relax us, they can reverse the molecular reactions in our DNA which cause ill-health and depression.

Ivana Buric et al analyze how the behavior of our genes is affected by different MBIs including mindfulness and yoga. Image credit: Nato Pereira.

When a person is exposed to a stressful event, the sympathetic nervous system the system responsible for the fight-or-flight response is triggered, in turn increasing production of a molecule called nuclear factor kappa B (NF-kB) which regulates how our genes are expressed.

NF-kB translates stress by activating genes to produce proteins called cytokines that cause inflammation at cellular level a reaction that is useful as a short-lived fight-or-flight reaction, but if persistent leads to a higher risk of cancer, accelerated aging and psychiatric disorders like depression.

However, people who practice mind-body interventions (MBIs) exhibit the opposite effect namely a decrease in production of NF-kB and cytokines, leading to a reversal of the pro-inflammatory gene expression pattern and a reduction in the risk of inflammation-related diseases and conditions, according to the study.

The inflammatory effect of the fight-or-flight response which also serves to temporarily bolster the immune system would have played an important role in mankinds hunter-gatherer prehistory, when there was a higher risk of infection from wounds, the authors said.

In todays society, however, where stress is increasingly psychological and often longer-term, pro-inflammatory gene expression can be persistent and therefore more likely to cause psychiatric and medical problems.

Millions of people around the world already enjoy the health benefits of mind-body interventions like yoga or meditation, but what they perhaps dont realize is that these benefits begin at a molecular level and can change the way our genetic code goes about its business, said lead author Ivana Buric, a PhD student at Coventry University, UK.

These activities are leaving what we call a molecular signature in our cells, which reverses the effect that stress or anxiety would have on the body by changing how our genes are expressed.

Put simply, MBIs cause the brain to steer our DNA processes along a path which improves our wellbeing.

More needs to be done to understand these effects in greater depth, for example how they compare with other healthy interventions like exercise or nutrition.

But this is an important foundation to build on to help future researchers explore the benefits of increasingly popular mind-body activities, Buric said.

_____

Ivana Buric et al. What Is the Molecular Signature of Mind-Body Interventions? A Systematic Review of Gene Expression Changes Induced by Meditation and Related Practices. Front. Immunol, published online June 16, 2017; doi: 10.3389/fimmu.2017.00670

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Study: Meditation, Yoga and Related Practices Can 'Reverse' DNA Reactions - Sci-News.com

GE and the Mayo Clinic back software to bring cancer-fighting gene therapies to market – TechCrunch

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GE and the Mayo Clinic back software to bring cancer-fighting gene therapies to market
TechCrunch
So GE (through its GE Ventures arm), the Mayo Clinic (through Mayo Clinic Ventures) and the venture investment firm DFJ have invested $13.75 million to back Vineti a software platform that the companies are billing as a solution to gene therapy's ...
GE Ventures, Mayo Clinic Ventures and DFJ Invest $13.75M in First Software Platform to Accelerate Cancer Cure ...GlobeNewswire (press release)

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GE and the Mayo Clinic back software to bring cancer-fighting gene therapies to market - TechCrunch

Human tissue model developed to test colon cancer drugs – Medical Xpress

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June 20, 2017 by Jane Langille This is a projection image displaying all of the colon organoid layers. The green represents cells that line the colon called epithelial cells; the red represents an increase in the number of cells that are proliferating; and the blue represents the staining of all cells. Credit: Dr. Miguel Crespo/Weill Cornell Medicine

The first-ever "disease in a Petri dish" platform that models human colon cancer derived from stem cells has been developed by Weill Cornell Medicine investigators, allowing them to identify a targeted drug treatment for a common, inherited form of the disease. The discovery also overcomes a long-standing challenge of using mice to research this form of cancer, as they do not typically develop the disease.

In the study, published June 19 in Nature Medicine, the scientists used human-induced pluripotent stem cells (iPSCs), which can in principle differentiate into any type of cell in the body, that were derived from the skin of two patients with an inherited form of colorectal disease called familial adenomatous polyposis (FAP). With FAP, large intestine cells develop into numerous polyps that for these patients eventually become colon cancer. Using iPSCs, they developed 3-D structures called colonic organoids that closely represented large intestine tissue systems and then performed drug testing.

"Creating an effective testing platform for human colon cancer has been a challenge for the entire field," said co-senior study author Todd Evans, the Peter I. Pressman, M.D. Professor in Surgery and professor of cell and developmental biology in surgery at Weill Cornell Medicine. "The protocols for modeling human colon disease for drug testing just weren't there until our team developed a stem-cell-based large intestine tissue system."

Colon and rectal cancers are the second-leading cause of cancer deaths in America. In 2017, it is estimated that 50,260 people will die from the disease and 135,430 new cases will be diagnosed.

The investigators confirmed through a variety of steps including genomic DNA sequencing and gene expression profiling that they had grown large intestine cells with either of two different FAP mutations, FAP8 or FAP9, and that a gene that when mutated allows FAP cells to grow out of control, called APC, was inactivated. They also created colonic organoids using stem cells derived from a person without FAP for comparison.

Next, they tested the colonic organoids with drugs to measure response. The researchers found that two drugs, XAV939 and rapamycin, significantly curbed cell proliferation; but also, significantly decreased growth in the organoids developed without FAP, suggesting that those drugs could harm healthy colon tissue. Another drug, geneticin, known for its ability to rescue gene activity for some types of mutations, successfully restored normal growth in the FAP9 organoids, yet had no impact on the FAP8 or healthy control organoids.

"Our results demonstrate that we can use this platform to model colon cancer and identify precision medicines that may work to target specific genetic mutations driving the disease," said co-senior author Shuibing Chen, associate professor of chemical biology in surgery and of biochemistry at Weill Cornell Medicine.

"The beauty is that we can make patient-specific organoids," Evans added, "increasing the likelihood of predicting which drugs may work and learn about any undesirable effects, all before we treat the patients."

Explore further: Three-pronged approach is key to precision medicine

More information: Miguel Crespo et al. Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing, Nature Medicine (2017). DOI: 10.1038/nm.4355

Journal reference: Nature Medicine

Provided by: Cornell University

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Human tissue model developed to test colon cancer drugs - Medical Xpress

Tapping gene therapy potential for inherited retinal diseases – ModernMedicine

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Reviewed by Edwin M. Stone, MD, PhD

Though gene therapy technology already exists to treat most inherited retinal disease, the current challenge is to drive down the costs of implementing the technologythus availing more patients with the benefits of treatments and possibly prevent inevitable visual deterioration.

Edwin M. Stone, MD, PhD, recounted the case of a 14-year-old boy with an inherited eye disease who was born deaf and received bilateral cochlear implants during the first years of his life. The boys visual acuity levels were 20/25 and 20/32 in the right and left eyes, respectively. Despite good visual acuity, more recently, he had been having difficulty seeing in dim light.

A Goldmann perimetry evaluation showed normal responses to large, bright stimuli. However, there was some restriction at the 12e and 14e isopters, explained Dr. Stone, director, Stephen A. Wynn Institute for Vision Research, and professor, Department of Ophthalmology and Vision Sciences, University of Iowa, Iowa City.

A fundus examination showed that both discs were normal and the vessels were slightly constricted. Some pigmentation was present in the midperipheral retina.

Based on these findings, deafness at birth, and retinitis pigmentosa at the beginning of the second decade of life, the patient was given a diagnosis of type I Usher syndrome. Molecular testing showed the presence of the two most common mutations in the USH1C gene, i.e., Val72Val (a splice variant) and Thr78insC.

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Tapping gene therapy potential for inherited retinal diseases - ModernMedicine

New Antibiotic Resistance Genes Found in Soil Microbes – The Scientist

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The Scientist
New Antibiotic Resistance Genes Found in Soil Microbes
The Scientist
The particularly surprising result is the discovery of a gene that encodes for an unusual small proline-rich polypeptide that confers resistance to the macrolide antibiotics, very important in human and animal medicine, Topp says. Macrolide ...

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New Antibiotic Resistance Genes Found in Soil Microbes - The Scientist

Scientists expanded the Capabilities of CRISPR gene editing technique – Tech Explorist

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CRISPR-Cas9, which is short for clustered, regularly interspaced short palindromic repeats and CRISPR-associated protein 9. The technique is faster, cheaper, more accurate, and more efficient than other existing genome editing methods.

For the CRISPR-Cas9 system to work, a bacterial defense protein got Cas9 seeks out an adjacent protospacer motif (PAM) that is present in the viral DNA yet not in the bacterial DNA. CRISPR-Cas9 has been harnessed for editing the human genome because such PAM sequences are also quite common in our DNA; however, genes that are not near a PAM cannot be targeted.

To conquer this problem, a team led by Benjamin P. Kleinstiver, a biochemist at MGHs Center for Genomic Medicine, engineered variations of a Cas9 protein that dont require a particular PAM to bind and cut DNA. The two new Cas9 variations, named SpG and SpRY, allow editing of DNA sequences at efficiencies not achievable with conventional CRISPR-Cas9 enzymes.

As engineered proteins target independently, they enable targeting of previously inaccessible regions of the genome.

Benjamin P. Kleinstiver, a biochemist at MGHs Center for Genomic Medicine, said,By nearly completely relaxing the requirement for the enzymes to recognize a PAM, many genome editing applications are now possible. And since almost the entire genome is targetable, one of the most exciting implications is that that the entire genome is druggable from a DNA-editing perspective.

Scientists are further planning to comprehend the function of these proteins. They also want to explore their unique capabilities for a variety of different applications.

Lead author Russell T. Walton, also of MGHs Center for Genomic Medicine, said,We have demonstrated that these new enzymes will allow researchers to generate biologically and clinically relevant genetic modifications that were previously unfeasible.

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Scientists Discover a Key to a Longer Life in Male DNA – New York Times

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New York Times
Scientists Discover a Key to a Longer Life in Male DNA
New York Times
But large-scale surveys of people's DNA have revealed few genes with a clear influence on longevity. It's been a real disappointment, said Nir Barzilai, a geneticist at Albert Einstein College of Medicine. Researchers are having better luck following ...

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Scientists Discover a Key to a Longer Life in Male DNA - New York Times

Precision medicine: Hype today but the promise is even bigger than we think – Healthcare IT News

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Precision medicine is more hype than reality right now but, at the same time, the incredible potentialit holds for the future is even greater than all the buzz teases today.

Thats what I came away with from the Precision Medicine Summit in Boston this week.

Lets look into the distant future: A patient walks into a hospital to meet with clinicians who run tests and pinpoint a biomarker for, say, Alzheimers. Then a gene surgeon does some on-the-spot genome editing. The patient walks out with that Alzheimers-free-for-life feeling.

Primary care andgenome sequencing will come to the forefrontto identify which patients can benefit in a future where genome editing is widespread, said Ross Wilson, principal investigator at the University of California Berkeleys Institute for Quantitative Biosciences.

Just how widespread can precision medicine get? Well, Eric Dishman, who spearheads the NIHs All of Us program said the program is starting off with the goal of attracting 1 million American participants but is already thinking about how toscale that into the billionsglobally.

Getting genomic data into an EHR The grand vision is to democratize research and apply more brainpower per problem to the most vexing medical issues.

Before we can get there, though, a lot has to happen to hammer out data gathering and sharing capabilities, retool the healthcare system so its much more adaptable to change and ultimately modernize IT infrastructure to support precision medicine and all the data that entails.

Robert Green, MD, a medical geneticist and physician-scientist at Brigham and Womens Hospital and Harvard Medical School predicted skirmishes,if not all-out war, over genetic and genomic screening practices: with clinicians and patients on one side, calling for as much information as they can possibly get, versus public health officials and others, warning about the unforeseeable consequences of over-screening.

Among the reasons that people are refusing to participate in genetic testing is fear of discriminationby life, disability or long-term care insurance companies, according to Mayo Clinic Department of Laboratory Medicine and Pathology attorney Sharon Zehe. She added that the whole scenario puts providers in an awkward position because even among patients who are willing to undergo screening, many dont want that data to live in their medical records.

Not that getting genetic data into a medical record is exactly easy. One of the fascinating accounts at the conference was Washington University genetics fellow and bioinformaticist Nephi Walton explaining how it took nine months working with Epic to include genetic results into the EHR. You can make a human in that time, Walton said to laughter from the audience as he turned to a slide with a baby picture.

Precision medicine architecture emerging While its true that todays EHRs and IT infrastructure are not ready for the big data needs of precision medicine and I saw that thesame thing is true about population healthlast month at least one architecture is emerging.

Indeed, the strategy of harnessing FHIR standards, with mobile phones as middleware and a common data repository outside the EHR, is an apt way to manage the demands of precision medicine, said John Halamka, MD, CIO of Beth Israel Deaconess Medical Center. The idea is to maximize what patients already have in their homes.

That approach also gives patients more controlover who can and cannot share their data, including researchers, which India Hook-Barnard, director of strategy and associate director of precision medicine at University of California, San Francisco, said it is both the right thing to do and sound science.

But even the architecture Halamka described and giving patients more control over data sharing will not conquer all precision medicine challenges, of course. Michael Dulin, MD, director of the academy for population health innovation at the University of North Carolina Charlotte said simply dumping a whole heap of genomic data on top of the already broken healthcare system, replete with huge variances and medical errors, may actually yield worse outcomes than we have today.

We have to use technology, we need AI, Dulin said. We cannot do this without it.

Walton noted that first we need simple artificial intelligence and machine learning algorithms just to clean up healthcares messy data so its suitable for more sophisticated AI tools.

Becoming'precision health' What was perhaps the boldest prediction to emerge from the conference came from Bryce Olsen, global strategist for Intels Health and Life Sciences unit: Patients will start asking for precision medicine in the second half of 2017 though many of them will not even realize what theyre requesting.

Patients are going to demand that doctors get a better understanding of underlying drivers of disease and defects in their tumor. Were going to see this for cancer first, Olsen said. Doctors that dont have good answers will see patients bounce.

Ill add one more to the mix: Precision medicine, in both term and concept, will be supplanted by the phrase precision health and, yes, this is distinct from how Im seeing digital health become digital medicine.

Precision health, said Megan Mahoney, chief of primary care in Stanfords population health division, is a fundamental shift to a more proactive and personalized approach that empowers people to live healthy lives.

Twitter:SullyHIT Email the writer:tom.sullivan@himssmedia.com

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CYP1B1, VEGFA, BCL2, and CDKN1A Affect the Development of Chronic Obst | COPD – Dove Medical Press

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Danlei Yang, 1 Ying Yan, 2 Fen Hu, 1 Tao Wang 1

1Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Peoples Republic of China; 2Department of Respiratory and Critical Care Medicine, Ningxia Peoples Hospital, Yinchuan 750002, Peoples Republic of China

Correspondence: Tao WangDepartment of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, Peoples Republic of ChinaTel +86-13971477320Email Tomwang_1095@163.com

Purpose: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by poor airflow. The purpose of this study was to explore the mechanisms involved in the development of COPD.Patients and Methods: The mRNA expression profile GSE100281, consisting of 79 COPD and 16 healthy samples, was acquired from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between COPD samples and healthy samples were analyzed using the limma package. Functional enrichment analysis for the DEGs was carried out using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool. Furthermore, DEG-compound pairs were predicted using the Comparative Toxicogenomics Database. The KEGG metabolite IDs corresponding to the compounds were also obtained through the MetaboAnalyst pipeline. Based on the diffusion algorithm, the metabolite network was constructed. Finally, the expression levels of key genes were determined using quantitative PCR (qPCR).Results: There were 594 DEGs identified between the COPD and healthy samples, including 242 upregulated and 352 downregulated genes. A total of 696 DEG-compound pairs, such as BCL2-C00469 (ethanol) and BCL2-C00389 (quercetin) pairs, were predicted. CYP1B1, VEGFA, BCL2, and CDKN1A were included in the top 10 DEG-compound pairs. Additionally, 57 metabolites were obtained. In particular, hsa04750 (inflammatory mediator regulation of TRP channels)-C00469 (ethanol) and hsa04152 (AMPK signaling pathway)-C00389 (quercetin) pairs were found in the metabolite network. The results of qPCR showed that the expression of CYP1B1, VEGFA, BCL2, and CDKN1A was consistent with that predicted using bioinformatic analysis.Conclusion: CYP1B1, VEGFA, BCL2, and CDKN1A may play important functions in the development and progression of COPD.

Keywords: chronic obstructive pulmonary disease, differentially expressed genes, enrichment analysis, disease metabolites, metabolite network

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Why sequencing the human genome failed to produce big breakthroughs in disease – The Conversation US

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An emergency room physician, initially unable to diagnose a disoriented patient, finds on the patient a wallet-sized card providing access to his genome, or all his DNA. The physician quickly searches the genome, diagnoses the problem and sends the patient off for a gene-therapy cure. Thats what a Pulitzer prize-winning journalist imagined 2020 would look like when she reported on the Human Genome Project back in 1996.

The Human Genome Project was an international scientific collaboration that successfully mapped, sequenced and made publicly available the genetic content of human chromosomes or all human DNA. Taking place between 1990 and 2003, the project caused many to speculate about the future of medicine. In 1996, Walter Gilbert, a Nobel laureate, said, The results of the Human Genome Project will produce a tremendous shift in the way we can do medicine and attack problems of human disease. In 2000, Francis Collins, then head of the HGP at the National Institutes of Health, predicted, Perhaps in another 15 or 20 years, you will see a complete transformation in therapeutic medicine. The same year, President Bill Clinton stated the Human Genome Project would revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases.

It is now 2020 and no one carries a genome card. Physicians typically do not examine your DNA to diagnose or treat you. Why not? As I explain in a recent article in the Journal of Neurogenetics, the causes of common debilitating diseases are complex, so they typically are not amenable to simple genetic treatments, despite the hope and hype to the contrary.

The idea that a single gene can cause common diseases has been around for several decades. In the late 1980s and early 1990s, high-profile scientific journals, including Nature and JAMA, announced single-gene causation of bipolar disorder, schizophrenia and alcoholism, among other conditions and behaviors. These articles drew massive attention in the popular media, but were soon retracted or failed attempts at replication. These reevaluations completely undermined the initial conclusions, which often had relied on misguided statistical tests. Biologists were generally aware of these developments, though the follow-up studies received little attention in popular media.

There are indeed individual gene mutations that cause devastating disorders, such as Huntingtons disease. But most common debilitating diseases are not caused by a mutation of a single gene. This is because people who have a debilitating genetic disease, on average, do not survive long enough to have numerous healthy children. In other words, there is strong evolutionary pressure against such mutations. Huntingtons disease is an exception that endures because it typically does not produce symptoms until a patient is beyond their reproductive years. Although new mutations for many other disabling conditions occur by chance, they dont become frequent in the population.

Instead, most common debilitating diseases are caused by combinations of mutations in many genes, each having a very small effect. They interact with one another and with environmental factors, modifying the production of proteins from genes. The many kinds of microbes that live within the human body can play a role, too.

Since common serious diseases are rarely caused by single-gene mutations, they cannot be cured by replacing the mutated gene with a normal copy, the premise for gene therapy. Gene therapy has gradually progressed in research along a very bumpy path, which has included accidentally causing leukemia and at least one death, but doctors recently have been successful treating some rare diseases in which a single-gene mutation has had a large effect. Gene therapy for rare single-gene disorders is likely to succeed, but must be tailored to each individual condition. The enormous cost and the relatively small number of patients who can be helped by such a treatment may create insurmountable financial barriers in these cases. For many diseases, gene therapy may never be useful.

The Human Genome Project has had an enormous impact on almost every field of biological research, by spurring technical advances that facilitate fast, precise and relatively inexpensive sequencing and manipulation of DNA. But these advances in research methods have not led to dramatic improvements in treatment of common debilitating diseases.

Although you cannot bring your genome card to your next doctors appointment, perhaps you can bring a more nuanced understanding of the relationship between genes and disease. A more accurate understanding of disease causation may insulate patients against unrealistic stories and false promises.

[ Youre smart and curious about the world. So are The Conversations authors and editors. You can read us daily by subscribing to our newsletter. ]

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Your hatred of heart-healthy veggies could be genetic – LocalNews8.com

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Super-tasters are extremely sensitive to bitterness, a common characteristic of many dark green, leafy veggies such as broccoli, cauliflower, cabbage and Brussels sprouts, to name a few. Super-tasters are extremely sensitive to bitterness, a common characteristic of many dark green, leafy veggies such as broccoli, cauliflower, cabbage and Brussels sprouts, to name a few. Related stories

ATLANTA - If certain vegetables have always made you gag, you may be more than a picky eater. Instead, you might be what scientists call a "super-taster:" a person with a genetic predisposition to taste food differently.

Unfortunately, being a super-taster doesn't make everything taste better. In fact, it can do the opposite.

Super-tasters are extremely sensitive to bitterness, a common characteristic of many dark green, leafy veggies such as broccoli, cauliflower, cabbage and Brussels sprouts, to name a few.

"The person who has that genetic propensity gets more of the sulfur flavor of, say, Brussels sprouts, especially if they've been overcooked," said University of Connecticut professor Valerie Duffy, an expert in the study of food taste, preference and consumption.

"So that [bitter] vegetable is disliked, and because people generalize, soon all vegetables are disliked," Duffy said. "If you ask people, 'Do you like vegetables?' They don't usually say, 'Oh yeah, I don't like this, but I like these others.' People tend to either like vegetables or not."

In fact, people with the "bitter gene" are 2.6 times more likely to eat fewer vegetables than people who do not have that gene, according to a new study presented Monday at the annual meeting of the American Heart Association.

"We wanted to know if genetics affected the ability of people who need to eat heart-healthy foods from eating them," said study author Jennifer Smith, a registered nurse who is a postdoc in cardiovascular science at the University of Kentucky School of Medicine.

"While we didn't see results in gene type for sodium, sugar or saturated fat, we did see a difference in vegetables," Smith said, adding that people with the gene tasted "a 'ruin-your-day' level of bitterness."

Our sense of taste relies on much more than a gene or two. Receptors on our taste buds are primed to respond to five basic flavors: salty, sweet, sour, bitter and umami, which is a savory flavor created by an amino acid called glutamate (think of mushrooms, soy sauce, broth and aged cheeses).

"But it's also smelling through the mouth and the touch, texture and temperature of the food," Duffy said. "It's very difficult to separate out taste from the rest. So when any of us say the food tastes good, it's a composite sensation that we're reacting to."

Even our saliva can enter the mix, creating unique ways to experience food.

"When we come to the table, we don't perceive the food flavor or the taste of food equally," Duffy said. "Some people live in a pastel food world versus others who might live in a more vibrant, neon food world. It could explain some of the differences in our food preference."

While there are more than 25 different taste receptors in our mouth, one in particular has been highly researched: the TAS2R38, which has two variants called AVI and PAV.

About 50% of us inherent one of each, and while we can taste bitter and sweet, we are not especially sensitive to bitter foods.

Another 25% of us are called "non-tasters" because we received two copies of AVI. Non-tasters aren't at all sensitive to bitterness; in fact food might actually be perceived as a bit sweeter.

The last 25% of us have two copies of PAV, which creates the extreme sensitivity to the bitterness some plants develop to keep animals from eating them.

When it comes to bitterness in the veggie family, the worst offenders tend to be cruciferous vegetables, such as broccoli, kale, bok choy, arugula, watercress, collards and cauliflower.

That's too bad, because they are also full of fiber, low in calories and are nutrient powerhouses. They're packed with vitamins A and C and what's called phytonutrients, which are compounds that may help to lower inflammation.

Rejecting cruciferous or any type of vegetable is a problem for the growing waistline and health of America.

"As we age as a population, vegetables are very important for helping us maintain our weight, providing all those wonderful nutrients to help us maintain our immune system and lower inflammation to prevent cancer, heart disease and more," Duffy said.

Food scientists are trying to develop ways to reduce the bitterness in veggies, in the hopes we can keep another generation of super-tasters from rejecting vegetables.

There's been some success. In fact, the Brussels sprouts we eat today are much sweeter than those our parents or grandparents ate. Dutch growers in the 90s searched their seed archives for older, less bitter varieties, then cross-pollinated them with today's higher yielding varieties.

People who already reject vegetables might try to use various cooking methods that can mask the bitter taste.

"Just because somebody carries the two copies of the bitter gene doesn't mean that they can't enjoy vegetables," Duffy said. "Cooking techniques such as adding a little fat, a little bit of sweetness, strong flavors like garlic or roasting them in the oven, which brings out natural sweetness, can all enhance the overall flavor or taste of the vegetable and block the bitterness."

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