TuesdayJul28,2020at6:56PM

LISBON - A group of Portuguese companies and research institutes announced they have launched a reusable face mask capable of inactivating the new coronavirus.

Credited with reducing the viral rate by 99 percent, the cloth mask passed tests carried out by the Joo Lobo Antunes Institute of Molecular Medicine.Creators claimed the mask has an innovative coating which helps to neutralize SARS-CoV-2, which causes COVID-19, when it comes into contact with the fabric.In a statement released to journalists, the scientists say it remains the same even after 50 washes.In a simplified manner, these tests consist of tissue analysis after contact with a solution containing a certain amount of virus, the viability of which is measured over time, said Pedro Simas, a researcher and virologist at the Joo Lobo Antunes Institute of Molecular Medicine.Manufactured in Portugal, the masks sold for 10 euros are being marketed in Portugal and throughout the European Union.

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Reusable face mask capable of inactivating virus launched in Portugal - Fall River Herald News

Hung Khong, MD, discusses antiestrogen and immunotherapy combinations in ER-positive, HER2-negative breast cancer.

Hung Khong, MD,a breast oncologist within the Chemical Biology and Molecular Medicine Program atMoffitt Cancer Center, discusses antiestrogen and immunotherapy combinations in ER-positive, HER2-negative breast cancer.

When immunotherapy is combined with a different drug in breast cancer, it is typically paired with chemotherapy, says Khong. The phase 2I-SPY 2 study combined pembrolizumab (Keytruda) with paclitaxel, or other chemotherapies, followed by doxorubicin and cyclophosphamide, for patients with ER-positive disease in the neoadjuvant setting.

However, it is known that in this setting, endocrine therapy works just as well, if not better than, chemotherapy in this patient population.In the United States, there is a great deal of comfort with combining immunotherapy with chemotherapy in the neoadjuvant setting, says Khong, but many studies are demonstrating that endocrine therapy works just as well and with less toxicity.

Different types of endocrine therapies are available, and the 2 major therapies are tamoxifen and the aromatase inhibitors. Tamoxifen has been shown to shift the T cells from a Th1 to Th2 phenotype and that will be impactful for a cancer treatment combinations, concludes Khong.

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Dr. Khong on Endocrine Therapy Combinations in ER+/HER2- Breast Cancer - OncLive

While many of us have avoided exposure to Covid-19 by sheltering in place, patients with advanced cancer have faced difficult choices about moving ahead with immune-compromising, but potentially life-saving treatments, and leaving the safety of their homes to receive infusions at hospitals or treatment centers.

Even more challenging, for many patients, the pandemic has altered the landscape of practically available treatment options. The best treatment for many patients with advanced cancer is often available only through a clinical trial. Trials traditionally have taken place at leading academic medical centers, which means patients often must travel long distances to participate and receive novel treatment.

Precision medicine has always been about getting the right drug to the right patient at the right time. I would argue not only do we in the oncology community need to embrace the promise of precision medicine more fully but also that the definition should be expanded to, the right drug to the right patient at the right time and in the right place. We need to make promising treatments, including the latest clinical trials, available locally.

Advancing Precision Medicine through Tumor Molecular ProfilingComprehensive tumor molecular profiling is foundational to precision medicine. While patients may have the same cancer type, variations within individual genomes may determine how well one patient responds to a certain treatment compared to another. Oncologists must have access to actionable molecular information to select the right treatment for their patients.

Since the human genome was mapped for the first time in 2003, a number of technological and scientific advances have made it possible for patients with cancer to receive comprehensive tumor molecular profiling results in less than two weeks, with costs increasingly covered by payers. Biomarkers are now widely used to identify patients for treatment with a specific therapeutic agent. Increasingly, cancer therapies are developed in tissue-agnostic indications, meaning they are approved based on molecular changes rather than the site of tumor. In June of this year, the U.S. Food and Drug Administration approved pembroluzumab (Keytruda) for the treatment of any solid tumor that is tumor mutational burden (TMB) high.

With these advances, one would think that every patient with advanced disease would receive tumor molecular profiling as a standard of care. However, this is not the case. Only about 15% of patients with advanced cancer receive comprehensive tumor profiling. Widespread deployment of tumor molecular profiling is emerging as a rate-limiting factor for how rapidly we can drive better outcomes for all patients with cancer.

Practical Challenges to Widespread Precision Oncology AccessWhy are patients not able to fully benefit from the promise of precision medicine? There are a several key barriers to access, including:

Addressing the ChallengeHow precision medicine companies, providers and health systems work together to develop and deploy solutions will determine how successfully we can deliver on the promise of precision cancer care. Some precision medicine companies are developing blood tests, called liquid biopsies, that identify potential tumor cells circulating in the blood with the goal of reducing reliance on tumor tissue biopsies. Others are undertaking educational campaigns to encourage broader uptake of comprehensive genomic testing. And there are companies that deliver a comprehensive precision oncology program to health systems, providing widespread and routine access to comprehensive tumor molecular profiling paired with local access to a portfolio of biomarker-guided clinical trials. A study presented by Kaiser Permanente Northern California at the 2020 ASCO meeting demonstrated how industry partnerships can enable health systems to implement and deliver a large-scale comprehensive precision oncology program.

Knowing which treatment is right can mitigate risk in unexpected ways as well. In a recent anecdote from our lab, tumor tissue from a 70-year old patient with advanced non-small-cell lung cancer was sequenced and found to have a rare, but highly actionable, gene fusion that could be treated with an orally available targeted therapy. Instead of having to attend multiple infusion visits for chemotherapy and immunotherapy that would result in substantial exposure risk to Covid-19, the patient can now receive a targeted therapy that can be taken at home with an expected dramatic response.

A Better FutureThis pandemic has taken a toll on everyone, and patients with advanced cancer have faced unique challenges. However, the opportunity before us is one to create the future we should all be working toward: a future where the right patient receives the right treatment, at the right time and in the right place. As we continue to work our way through this current pandemic, lets envision a future where every patient with cancer has access to the latest in precision medicine by implementing broad-scale genomic testing and democratizing access to clinical trials so that whatever environment we face, cancer patients will always receive the best care.

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Delivering on the promise of precision cancer medicine and why it matters even more during a pandemic - MedCity News

A new study of Neanderthal DNA suggests our species extinct relatives may have been particularly sensitive to pain, reports Ewen Callaway for Nature.

Neanderthals disappeared some 40,000 years ago, but some humans living today retain bits of Neanderthal DNAevidence that our species once interbred. Though they hunted large, dangerous animalsincluding bison, mammoths and cave bearsin frigid climes, Neanderthals may be the source of a genetic variant associated with increased sensitivity to pain in modern humans, accoring to the new research published last week in the journal Current Biology.

Researchers looking to compare Neanderthals DNA to modern humans have historically only had a few low resolution genomes to choose from. But the team behind the new paper were able to produce three high-quality Neanderthal genomes from genetic material recovered from caves in Croatia and Russia, per Nature.

Researchers found a mutation to a gene called SCN9A that encodes a protein involved in sending pain signals to the spinal cord and brain on both chromosomes of all the Neanderthal genomes. Its presence on both chromosomes of all three genomes suggests it was common in the Neanderthal population, according to Nature.

The mutation to SCN9A codes for three amino acid differences compared to modern humans, researchers tell Brooks Hays of United Press International (UPI).

"[The gene] is unusual in having three differences unique to Neandertals in the protein it encodes," Svante Pbo, a geneticist at the Max Planck Institute for Evolutionary Anthropology and co-author of the study, tells UPI.

Through experiments, the researchers determined that the Neanderthal mutation lowers the threshold required for the bodys nerves to send pain signals to the spinal cord and brain, which could also potentially make those sensations more painful, reports Emma Betuel for Inverse.

People have described it as a volume knob, setting the gain of the pain in nerve fibres, Hugo Zeberg, the papers lead author and a researcher at the Max Planck Institute for Evolutionary Anthropology as well as the Karolinska Institutet, tells Nature.

The researchers used a database of more than 362,944 genomes of British people to investigate whether this mutation was present in modern humans. Only 0.4 percent of Brits who responded to a questionnaire about their pain symptoms had a copy of the Neanderthal mutation to the SCN9A gene, per Inverse, but those who had the mutation were 7 percent more likely to report pain at least one pain symptom. Though its true older folks in the survey tended to report increased pain, the researchers found that people with the Neanderthal variant to SCN9A were reporting pain typical of someone about 8.5 years older than their actual age.

In an emailed statement to Amy Woddyatt of CNN, Zeberg notes that other genetic variants impact peoples experience of pain that are unrelated to Neanderthal ancestry, and that not everyone with a low pain threshold could blame it on Neanderthals.

"Whether Neandertals experienced more pain is difficult to say because pain is also modulated both in the spinal cord and in the brain," Pbo says in a statement. "But this work shows that their threshold for initiating pain impulses was lower than in most present-day humans."

Neuroscientist Cedric Boeckx of the Catalan Institute for Research and Advanced Studies tells Nature that, this is beautiful work. Boeckx, who was not involved in the research, says the paper shows how studying modern humans can illuminate facets of Neanderthal physiology.

But Gary Lewin, a neuroscientist at the Max Delbrck Center for Molecular Medicine in Germany who was not involved in the research, tells Nature that the effect caused by the Neanderthal mutations to SCN9A is small, especially compared to other mutations associated with chronic pain. Lewin further wonders what adaptive advantage increased pain sensitivity might have conferred.

"Pain is not necessarily a bad thing," Zeberg tells Inverse, noting that bad sensations help us avoid injury and survive.

Zeberg tells CNN that he hopes in the future the findings of genetic investigations such as this one could help develop personalized medical treatments based on the patients genes.

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Neanderthals May Have Been More Sensitive to Pain Than Most Humans - Smithsonian Magazine

In the early months of the COVID-19 pandemic, Ben Fried made a difficult decision: He stopped riding New York Citys subway system.

He was not alone. Ridership on the citys notoriously packed commuter trainsdropped92% in mid-April, when New York emerged as an epicenter of the global health crisis.

For Fried, the decision was especially tough because he serves as communications director for TransitCenter, an advocacy group that touts the environmental benefits of mass transit.

But as the virus spread, those benefits were overshadowed by the risk of contagion in the enclosed spaces of subway cars.

I think the prevailing attitude then was, If you dont need to ride, dont ride, Fried recalled in a recent phone interview.

Since those first fateful months, however, Fried has ventured back onto the subway with his wife. And hes become part of a vocal group of advocates saying the initial fears of mass transit were overblown.

Those advocates say there is scant evidence tying major coronavirus outbreaks to buses and trains. On the contrary, they say, transit can play a crucial role in the pandemic era by reducing air pollution that makes people more susceptible to COVID-19.

Two prominent proponents of this argument are Janette Sadik-Khan, the former commissioner of the New York City Department of Transportation, and Seth Solomonow, the co-author of Streetfight: Handbook for an Urban Revolution.

In a recentopinion pieceinThe Atlantictitled Fear of Public Transit Got Ahead of the Evidence, the pair wrote that many have blamed subways and buses for coronavirus outbreaks, but a growing body of research suggests otherwise.

The piece noted that epidemiologists use the term cluster to describe major coronavirus outbreaks. A cluster is defined as more than three cases that can be traced to a common event or venue, excluding transmission within households.

In Paris, a recentstudyfound that none of the citys 150 coronavirus clusters from early May to early June originated on the citys transit systems,Le Parisiennewspaperreported.

The study was conducted by researchers at Sant Publique France, the national public health agency. It was published June 4.

As of July 15, four transport clusters had been identified in Paris, accounting for roughly 1% of 386 total clusters, according to data from the agency.

Its a similar situation in Japan, where researchers failed to connect a single cluster to the countrys commuter trains, said Hitoshi Oshitani, a virologist and public health expert at Tohoku University.

The vast majority of the clusters were instead traced to gyms, bars, live music venues, karaoke rooms and similar establishments where people come in close contact with one another, Oshitani said in an email to E&E News.

The evidence is less robust in the United States, which lags other developed countries in contact tracing and coronavirus testing.

Contact tracing involves determining an infected persons close contacts, which the Centers for Disease Control and Preventiondefinesas any individual within six feet of an infected person for at least 15 minutes.

Epidemiologists interviewed for this story couldnt point to comparable research on contact tracing that focused on U.S. transit systems.

The epidemiologists also were unsure whether riding transit in America was riskier than other activities amid the pandemic, such as going to the gym or eating at a restaurant with outdoor seating.

How risky is it? Well, theres nothing in life that doesnt have risk. And in the COVID era, everybody is trying to assess what risks theyre willing to take, said Ruth Collins, associate professor of molecular medicine at Cornell University.

Its difficult to classify the danger of any activity during the pandemic given the lack of robust data, Collins said. But in general, she noted, riding transit is much safer if all passengers are wearing face masks that cover their noses and mouths.

Melissa Perry, a leading epidemiologist and chair of the Department of Environmental and Occupational Health at George Washington Universitys Milken Institute School of Public Health, agreed with this assessment.

When you have universal adherence and compliance with mask use, thats when you are majorly reducing the risk for transmitting the virus, Perry said.

Both mask wearing and physical distancingor keeping 6 feet apart from fellow passengersare the most important considerations, she said. They take precedence over cleaning and disinfecting surfaces, which are much less likely to spread the coronavirus than respiratory droplets, according to the CDC.

Still, transit poses the risk of high-touch surfaces such as handrails and elevator buttons that a lot of people have touched before you, Perry said.

Not all surfaces are created equal, she said. With the standard surfacelets say you pick up an item in the grocery store or get a box in the mailthe likelihood of getting COVID-19 is very low. With public transportation, what were talking about is high-touch surfaces. And those are higher-risk surfaces.

Regardless of its relative safety, transit can play a crucial role in combating climate change and air pollution, advocates said.

Public transportation produces far less greenhouse gas emissions per mile than cars, according tofindingsreleased by the Department of Transportation under President Obama. Leading the pack are subways, which boast 76% less carbon emissions than the average vehicle carrying a single person.

In addition to planet-warming pollution, transit also produces fewer criteria air pollutants such as particulate matter and nitrogen dioxide.

Recent research from Harvard University, which has not yet been peer-reviewed, found a tentative link between higher exposure to particulate matter and higher mortality rates from COVID-19, particularly among communities of color (Greenwire, April 7).

Shared transportation is so critical to keeping cities congestion-free. And congestion exacerbates the air quality issues that are such a huge part of the calculus of the public health crisis now, said Brianne Eby, a senior policy analyst at the Eno Center for Transportation, a Washington-based think tank.

Fried, the communications director for TransitCenter, agreed.

If everyone who has a car starts to drive instead of taking the train or the bus, then particulate emissions are going to rise, and thats going to exacerbate a lot of the health disparities that have hit communities of color especially hard during COVID, Fried said.

And then theres the long-term climate risk associated with rising carbon emissions, he added. So if we see a big shift from transit to driving, thats going to put climate goals out of reach.

Reprinted from Climatewire with permission from E&E News. E&E provides daily coverage of essential energy and environmental news atwww.eenews.net.

Editors Note (7/30/20): Our partners at Climatewire have edited thisstoryafter posting to correct the sourceof information on the transport clusters identified in July 15 and to remove a comment regarding the June 4 study.

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There Is Little Evidence That Mass Transit Poses a Risk of Coronavirus Outbreaks - Scientific American

SIX patients who were suffering from the acute coronavirus disease 2019 (Covid-19) were cured through the stem cell technology using blood from preserved umbilical cords.

The revolutionary method of curing the dreaded virus, which originated in China and has spread worldwide, was announced by The Medical City (TMC) hospital in Pasig City.

Health Secretary Francisco Duque 3rd was informed of the breakthrough in treating the pandemic illness through a letter sent by Dr. Eugenio F. Ramos, TMC president and chief executive officer, on Thursday, July 23.

Our government, particularly the Department of Health, can take pride in the fact that the Philippines is not behind at all in innovative practice in medicine, said Ramos in his letter to Duque.

The TMC has been experimenting with stem cell therapy since 2015 through its Institute of Personalized Molecular Medicines stem cell program.

The stem cell experiment was made on seven Covid-19 patients who were so ill they were about to be intubated.

Intubation means inserting a tube into the patients mouth that reaches the trachea to allow him/her to breathe through a lung machine.

Six of the seven patients had recovered, the TMC said; one was so ill he died during the procedure.

As I told you this morning, we would have wanted to complete at least 10 Covid-19 cases before informing you, but it might be taken against us if we kept this knowledge from the public too long while patients are dying and no single drug seems to work, Dr. Ramos told Duque.

Ramos simplified for the public how the stem cell therapy works:

Stem cells are very young cells from the body that can be differentiated into whatever cell lines (lung, heart, kidney, liver, skin, etc.) that the body needs when it needs them, e.g., when an organ is injured or deteriorates. Stem cells can be triggered or infused to do [repair] work.

In severe Covid-19 cases, what triggers a cascade of inflammatory cells (called cytokines) is the injury caused by the virus. The lungs, in particular, become inflamed and the respiratory function rapidly deteriorates leading to death.

Before the cascade happens in which case the patient is in a severe condition probably requiring intubation the infusion of mesenchymal stem cells collected [from] the umbilical cord and grown in [the regenerative medicine laboratory of TMC into the patients veins, takes place.

A total of four infusions are given over a short period of a few days. These messenchymal stem cells rally the cells in the lungs to fight the cytokines.

In short, the stem cells from the umbilical cord produce new cells to replace those damaged by the virus in the lungs, leading to the patients recovery.

The umbilical cord is rich in nutrients to rebuild destroyed tissues, according to Ramos.

TMCs stem cell program also makes use of bone marrow taken from a patients spine to cure cancer.

But the bone marrow stem cell is also used to delay the aging process in elderly patients.

TMC had the most number of bone marrow transplantation for blood cancers, with more than 90 percent survival rate, said Dr. Ramos.

Since 2015, a total of 112 patients have enrolled in TMCs regenerative medicine program.

Of the total, 57 percent were cancer patients and 43 percent were non-cancer patients, said TMCs Dr. Michelle Joy Baldorado-de Vera.

Oncologists (doctors who specialize in cancer) are part of the regenerative medicine program Alan Olavere, Marina Chua-Tan and Josephine Tolentino.

Other members are hematologists (blood doctors) Norma Ona and Alma Calavera, neurologists John Tiongson and Marc Joseph Buensalido, and immunologist Michelle de Vera.

Dr. Sam Bernal, a Filipino American who grew up in the United States, is a consultant to the program.

Bernal is a molecular scientist and an oncologist who has been into stem cell technology for decades.

He was part of the foreign group that was tapped by the government for technology transfer.

Former Health secretary Alfredo Bengzon, who is a part owner of TMC, engaged Bernal to pioneer stem cell therapy in the country.

TMC has had foreign patients who underwent stem cell therapy, but refuses to disclose their number.

As is the norm among Filipinos who have the crab mentality, TMCs stem cell program has been criticized by fellow doctors.

Weve been defending the program from the outset, said Dr. Ramos.

But its not only TMC that has been into stem cell therapy; the other hospitals are the Makati Medical Center and the governments National Kidney and Transplant Institute.

Original post:

A breakthrough: Stem cell therapy cures Covid-19 The Manila Times - The Manila Times

What if you could age slower and maintain your ability to be active and enjoy your family well into your 70s or 80s or beyond? What if you could delay the onset of chronic disease by almost a decade? Well, that is no longer a dream. Thanks to advances in the science of aging and chronic disease, we know that there are things that you can do now to impact your health and, perhaps, your longevity.

Lets start our discussion by diving into some of the basic science related to prolongation of a healthy lifespan. Dont worry, we are going to start with a video and its going to be fun.

First, check out this very entertaining short TED talk by Cynthia Kenyon who is a top scientist at the University of California at San Francisco Medical School. Then come back to this post for an expanded discussion.

The importance of Dr. Kenyons work and that of contemporary aging researchers is that they showed, for the first time, that aging and age-related chronic diseases arent things that just happen to us. [1] They are, in fact, related to an evolutionarily-conserved complex, highly regulated, and interconnected series of biochemical pathways.

Central to these pathways is a molecule called mTOR which stands for mechanistic Target of Rapamycin. It is so-named because rapamycin, a naturally occurring substance, inhibits the many of the activities of mTOR triggering a variety of metabolic and clinical outcomes. The most well-known of which is the extension of healthy lifespan.[2, 3]

mTOR exists as a complex of proteins called mTOR complex or mTORC. There are actually two different forms mTORC known as mTORC1 and mTORC2. Activation of the complexes occurs via different pathways. Once activated the mTOR complexes, in turn, activate or inhibit pathways critical to cell function. [2, 3]

mTORC1 and 2 are activated or inactivated depending on the availability of nutrients in the cells environment (e.g., glucose, amino acids and various growth factors). In fact, you can think of mTORC as integrating and responding to the energy status of the cells environment.

When times are good and energy, oxygen, nutrients, and growth factors is plentiful, mTORC1 is activated and stimulates metabolic pathways that lead to growth. When times are tough, those pathways are suppressed and the pathways related to survival are activated.

Here are some of the cellular functions mTORC1 regulates [2,4]:

The last two functions are inhibited when energy, nutrients, and growth factors are plentiful.

mTORC2 is activated by insulin and growth factors. [2,4] It regulates the following:

Rapamycin inhibits most but not all of the activities of mTORC1. However, it does not inhibit mTORC2 in the short run. There is some evidence that chronic administration of rapamycin, however, can inhibit mTORC2.[4] Further, there are important feedback pathways between mTORC1 and mTORC2.

Living organisms on our planet are subject to varying availability of nutrients and other sources of energy. In order to survive, they must be able to sample the energy availability in their surroundings and adjust accordingly.

mTOR-linked pathways provide that mechanism. Receptors found in cell membranes have both an external-facing component and an internal-facing component. The external component binds to nutrients, such as glucose, amino acids, oxygen, and various growth factors. As described above, this leads to the activation or inactivation of different intermediate proteins that ultimately activate or inhibit mTOR.

For example, during times of energetic stress, a protein known as AMPK is activated. This in turn inhibits mTORC1 and leads to activation or inhibition of other intermediate compounds. The result is a state of cellular activity that favors prolongation of lifespan.[5]

Although the pathways are incompletely understood, it is of note that dietary restriction a self-induced famine in a way is also associated with longevity.[5] We must remember, though, because of complex feedback loops, the ability to prolong lifespan via these mechanisms is not limitless.

On the other hand, during times of plenty, the availability of glucose increases. In addition to reducing the activation of AMPK, it also triggers the release of the hormone insulin and insulin-like growth factor). This leads to mTOR activation and creation of a state that favors growth and development including such things as elevated lipid levels that favor the development of chronic diseases.

Understanding the molecular biology of the mTOR pathways has some very practical applications. For example, as we have already pointed out, restricting calories is associated with reduced levels of some factors that inhibit mTORC1 and is associated with lifespan extension.[5] Intermittent fastingand exercise also reduce mTOR activity.

Also, restricting carbohydrates in people with Type 2 diabetes is known to lower blood glucose, insulin, and IGF-1 levels. The benefits of this type of diet does not require weight loss, although many do lose weight with carbohydrate restriction. [6] In fact, some experts have called for dietary carbohydrate restriction to be the first intervention prescribed in diabetes management. [6]

The prevailing American high-carbohydrate, high-fat fast-food diet, on the other hand, drives extra calorie intake and as well as higher levels of the factors that activate mTORC1. This, unfortunately, leads to metabolic conditions that accelerate the development of chronic diseases such as diabetes and heart artery problems.[6]

Metformin is the most commonly prescribed drug for Type 2 diabetes. It interferes with the same signaling pathways that we have been discussing. Specifically, it leads to the reduction of glucose, IGF-1, insulin levels. This, in turn, leads to inhibition of mTORC1. This results in a metabolic state that favors important health outcomes, such as:

Further, the drug has been proven to be safe with relatively few serious side effects. And, it is cheap, making it accessible even for people without health insurance.

Metformin is the also first drug approved by the FDA to enter a clinical trial to assess its effect on prolongation of a healthy lifespan. According to American Association for Aging Research, the Targeting Aging with Metformin (TAME) trials are a series of nationwide, six-year clinical trials at 14 leading research institutions across the country that will engage over 3,000 individuals between the ages of 65-79.

These trials will test whether those taking metformin experience delayed development or progression of age-related chronic diseasessuch as heart disease, cancer, and dementia.

As mentioned, the drug rapamycin inhibits mTORC1 activity and is associated with a prolonged lifespan. However, systemic rapamycin has unacceptable side effects, so its use is limited in humans.

It is used, however, for local applications. One example is the use of Sirolimus (the brand name of rapamycin) in early versions of drug-eluting stents (DES) used to treat coronary artery disease. [7]

More recently, scientists have modified rapamycin to create less toxic forms of the drug. They are known as rapalogs. These include everolimus, zotarolimus, and biolimus. Together with improved stent platform materials, the use of these DESs have been shown to lower thrombotic events related to the stents. [8]

There are a number of drugs that are used for cardiovascular disease that specifically impact the mTORC pathways by various mechanisms. For example, lisinopril (ACE inhibitor), losartan (angiotensin receptor blocker), atorvastatin (statin), and eplerenone (mineralocorticoid receptor blocker) all reduce oxidative particle formation. Indirectly, this lead to the inhibition of mTORC.

This, as we know, leads to metabolic changes that favor healthy aging. These effects on the mTOR-related signaling pathways may be the reason why these medications lower the risk of heart attack and stroke more than they reduce the target risk factors of blood pressure, lipid, and glucose levels.

On the other hand, tobacco smoke increases oxidative stress and favors the activation of mTORC pathways. This may eventually lead to Chronic Obstructive Lung Disease (COPD) and lung cancer.

Interfering with this core signaling is a form of precision medicine that impacts the molecular biology that causes cardiovascular disease, cancer, and accelerated aging. These medications are antioxidants that work.

Here is the most shocking insight. The same core signaling that causes accelerated aging, chronic disease, and ultimately death is essential to produce a perfectly developed newborn. At the moment of conception, there is a single cell that will ultimately become all the cells in the body with their vastly different functions.

The DNA for every cell in your body is the same. Epigenetic regulation determines which genes are turned on or off in a particular cell type. For example, normal EGFR function is necessary to establish pregnancy successfully at the very beginning of life. However, it contributes to chronic disease development later.

Angiotensin II is required to form a normal fetal kidney, but inappropriate activation later in life contributes to developing hypertension, chronic kidney disease, and congestive heart failure.

mTOR activation via nutrient sensing and growth factor signaling in the fetus directs a master symphony of switching genes on in just the right place, at just the right time, with just the right intensity for an exact amount of time to produce a perfect infant.

However, the same genes that are essential to coordinate normal development cause disease and death with chaotic activation later.

The human genome project did not give us the answers for accelerated aging and common chronic diseases. These problems are caused by normal genes that are inappropriately switched on later in life by things like aging, unhealthy diets, and tobacco smoke.

Specific highly effective generic medications with few side effects can block the signaling from those genes and lead to dramatically better clinical outcomes at a lower cost. Caloric restriction, intermittent fasting, exercise, and the specific medications mentioned all impact the same signaling.

New science, new systems, and new payment models can improve our health at a lower cost. All the necessary elements are available. It is time to bring the stakeholders together and get started.

2. Papadopoli D, Boulay K, Kazak L, et al. mTOR as a central regulator of lifespan and aging [version 1; peer-review: 3 approved] latest versions as of 07/27/20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611156/pdf/f1000research-8-18802.pdf

3. Weichhart T. mTOR as regulator of lifespan, aging and cellular senescence. Gerontology. (2018) 64(2):127-134.https://pubmed.ncbi.nlm.nih.gov/29190625/

4. Samidurai A, Kukreja R, Das A. Emerging role of mTOR signaling-related miRNAs in cardiovascular diseases. Oxidative Medicine and Cellular Longevity. Volume 2018, Article II6141902, 23 pages https://www.hindawi.com/journals/omcl/2018/6141902/

5. Longo V, Antebi A, Bartke A, et al. Interventions to Slow Aging in Humans: Are We Ready? Aging Cell (2015) 14, 497-510. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4531065/

6. Feinman R, Pogozelski W, Astrup, A, et al. Dietary carbohydrate restriction as the f first approach in diabetes management: Critical review and evidence base. Nutrition(2015) 31:1-13.https://www.sciencedirect.com/science/article/pii/S0899900714003323

7. Serruys P, Regar E, Carter A. Rapamycin eluting stent: the onset of a new era in interventional cardiology.Heart(2002) 87:305-305.https://www.researchgate.net/publication/277539488_Rapamycin_eluting_stent_the_onset_of_a_new_era_in_interventional_cardiology

8. Im E, Hong, M-K. Drug-eluting stents to prevent stent thrombosis and restenosis (2016) 14(1):87-104 https://pubmed.ncbi.nlm.nih.gov/26567863/

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mTOR and the Science of Aging and Chronic Disease - The Doctor Weighs In

In the United States, two-thirds of Alzheimers disease diagnoses are in women. While its well-established there are indeed sex differences in the risk and prevalence of Alzheimers, scientists are unsure about why women are more likely to get this disease. Even when taking womens average longer lifespans into account, the increased risk remains, indicating that biological sex differences influence how the disease begins and spreads.

To increase understanding, an NIA scientific team used data and samples from participants in the Baltimore Longitudinal Study of Aging (BLSA) along with animal and human cell models to zero in on sex-based differences in how the brain metabolizes sugar as a culprit and potential therapeutic target. Their findings were published the journal Acta Neuropathologica.

Prior studies have shown that women with Alzheimers carry higher levels of amyloid plaques and neurofibrillary tangles than male counterparts. Women also have more severe cognitive symptoms compared to men at the same disease stages. Based on previous work in the field, the NIA team knew that changes in brain glucose metabolism are seen decades before cognitive impairment becomes obvious. They focused on a cross-species approach to further investigate why problems metabolizing glucose (sugars) may be a prelude to dementia-like symptoms. To compare metabolic activity, they analyzed brain tissue and blood samples from BLSA participants who had Alzheimers, along with lab-grown human cell models of Alzheimers, two Alzheimers mouse models, and two specialized strains of flatworms.

The scientists observed that Alzheimers caused impairment in the mitochondria (cell powerhouses") of brain synapses junctions for chemical or electrical signals between neurons in female, but not male, mice. Next, the mouse and human cell models consistently showed that the brain and body try to adapt to this metabolic impairment by shifting from processing glucose (sugars) to lipids (fatty acids.) The scientists then proved that this metabolic shift is needed for survival in both worms and human cell culture Alzheimers models.

Interestingly, further study of animal models and human cell samples showed that males were better able than females to adapt to this metabolic shift at the molecular level. These significant differences in mitochondrial mechanisms and metabolic responses to Alzheimers may explain why there are sex-related differences in risk and disease development.

This study also identified specific molecular and metabolic impairment sites and pathways in mice and humans that are likely connected to sex differences. Further research is needed to develop precision medicine targets for interventions.

This research was funded in part by NIA grant ZIA AG00073817 and the NIA Intramural Research Program.

Reference: Demarest TG, et al. Biological sex and DNA repair deficiency drive Alzheimer's disease via systemic metabolic remodeling and brain mitochondrial dysfunction. Acta Neuropathologica. 2020;140(1):25-47. doi: 10.1007/s00401-020-02152-8.

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A shift in brain glucose metabolism may help explain women's increased risk of Alzheimer's disease - National Institute on Aging

Global Bioinformatics Service Market presents comprehensive insights into the present and upcoming industry trends, enabling the readers to identify the products and services, hence driving the revenue increase and effectiveness. The research report presents a complete breakdown of all the major factors affecting the market on a global and regional scale, including drivers, constraints, threats, challenges, opportunities, and Bioinformatics Service industry-specific trends. Further, the report mentions global facts and figures along with downstream and upstream analysis of leading players.

The study gives answers to the following key questions:

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Major Players:

Agilent TechnologiesQIAGENCD GenomicsThermo Fisher ScientificIlluminaStrand Life SciencesBGI GroupDNANEXUSBiomax InformaticsGene CodesCreative-BiolabsFIOS GenomicsGene CodeDNASTARBiomatters GeneiousPerkinElmerGSL Biotech LLC (SnapGene)Premier Biosoft

This research presents Bioinformatics Service market growth rates and the market value based on market dynamics, growth factors. The complete knowledge is based on the newest innovation in the business, opportunities, and trends. In adding up to SWOT analysis by key suppliers, the report contains an all-inclusive market analysis and major players landscape.

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The regional segmentation covers:

Segmentation by Type:

Drug DevelopmentGene TherapyMolecular MedicineVeterinary ScienceOthers

Segmentation by Application:

Academics and Research CentersPharmaceutical and Biotechnology IndustriesForensics LaboratoriesOthers

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Report Objectives

Global Bioinformatics Service Market Size, Status and Forecast 2020-2024

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Global Bioinformatics Service Market Report COVID-19 Outbreak Development Trends, Threats, Growth Opportunities and Competitive Landscape in 2024 -...

Light and medicine have a long and intertwined past. Most civilizations throughout history appear to have understood that there was a connection between sunlight and good health. The ancient Egyptians worshipped the sun, with Ra the sun god often described as the king of all gods. Both the ancient Romans and Greeks used sunbaths to maintain good health. Heliotherapy (helio is Greek for sun) was deemed an important part of athletic training in ancient Greece as it was thought to improve muscle health.The link between light and medicine was exemplified by Niels Finsen a pioneer of modern phototherapy. Finsen was awarded the 1903 Nobel Prize in Physiology or Medicine in recognition of his contribution to the treatment of diseases, especially lupus vulgaris, with concentrated light radiation, whereby he has opened a new avenue for medical science.

By the end of the first quarter of the 20th century, the use of phototherapy for medical purposes, in northern Europe and some regions of North America, was considerable. Prof. Dirk Trauner says that whist phototherapy has been hugely successful, the chemistry that currently mediates the effects of light in phototherapy is relatively simple.

Trauner and his team set out to develop more sophisticated ways to harness light therapeutically. We have been joined in this effort by a growing number of colleagues, explains Trauner. Ben L. Feringa is one such colleague, who was jointly awarded the Nobel Prize in Chemistry for the design and synthesis of molecular machines in 2016.

Trauners work is based photopharmacology, an innovative approach whereby light is used to activate and deactivate therapeutics and/or biological processes.

However, by introducing photopharmacology, Trauner explains that it is possible to add a further level of control to the PROTAC. One can target their [PROTACS] action to specific tissues or tumors, avoiding side effects elsewhere in the body, says Trauner.

Whilst phototherapy is typically applied to the surface of the skin, PHOTACs could be switched on and off within the body by means of an endoscope combined with a light source, or by using an implanted LED.

Furthermore, in future, by using different colors of light a concept known as color dosing it could be possible to control the activity of PHOTAC-based therapeutics even more precisely. By regulating the concentration of the active or switched-on form of the PHOTAC, dosage of the drug could be altered within the body gradually.

PHOTACs do work like PROTACS but can be activated or inactivated at will as long as light-delivery is possible. Light-delivery in the human body has become quite sophisticated in recent years. New technologies for light delivery are emerging, largely driven by optogenetics and photodynamic therapy, concludes Trauner.

Reference: Reynders, et al. (2020). PHOTACs enable optical control of protein degradation. Science Advances. DOI: 10.1126/sciadv.aay5064Dirk Trauner was speaking with Laura Elizabeth Lansdowne, Senior Science Writer for Technology Networks.

Excerpt from:

Photopharmacology Switching Drugs On and Off With Light - Technology Networks

The COVID-19 pandemic didnt just transform how we work and communicate. It also accelerated the need for more proactive health measures for chronic health problems tied to diet. Such problems have emerged as a top risk factor for coronavirus and people with poor metabolic health accounted for half of COVID-19 hospitalizations in some regions around the world. The resulting high numbers led the authors of a report in The Lancet to issue a call for more resources to tackle metabolic health to avoid needless deaths.

Thankfully, new tools have been developed to offer comprehensive understanding of nutrition. This expertise and technology wont just help us tackle metabolic health it could help us finally fully realize the power of plants to improve health and wellness outcomes.

The first global pandemic in more than 100 years, COVID-19 has spread throughout the world at an unprecedented speed. At the time of writing, 4.5 million cases have been confirmed and more than 300,000 people have died due to the virus.

As countries seek to recover, some of the more long-term economic, business, environmental, societal and technological challenges and opportunities are just beginning to become visible.

To help all stakeholders communities, governments, businesses and individuals understand the emerging risks and follow-on effects generated by the impact of the coronavirus pandemic, the World Economic Forum, in collaboration with Marsh and McLennan and Zurich Insurance Group, has launched its COVID-19 Risks Outlook: A Preliminary Mapping and its Implications - a companion for decision-makers, building on the Forums annual Global Risks Report.

The report reveals that the economic impact of COVID-19 is dominating companies risks perceptions.

Companies are invited to join the Forums work to help manage the identified emerging risks of COVID-19 across industries to shape a better future. Read the full COVID-19 Risks Outlook: A Preliminary Mapping and its Implications report here, and our impact story with further information.

We know that plants are critical for health, but do not fully understand why. Humans have not mapped the breadth of what plants offer, nor have we pinpointed the specific biological mechanisms of action triggered in our bodies when we eat them. This knowledge gap exists at the molecular level, with a need to understand how phytonutrients tiny plant molecules with anti-inflammatory, cardioprotective and neuroprotective properties work in our bodies. In fact, the scientific community refers to the vast world of phytonutrients as the dark matter of nutrition because less than 1% of these molecules have been catalogued to date. The opportunity to learn more about phytonutrients and further tangibly connect their impact to health is massive.

Technologies, such as Artificial Intelligence, are helping researchers learn more about the biological connections between plants and humans. For instance, Brightseed has created a powerful artificial intelligence called Forager, which coupled with advanced metabolomics instrumentation, systematically identifies unknown plant compounds and predicts their likely roles in human health. Thus far, the technology has predicted beneficial phytonutrients for many important health conditions.

Recently, in collaboration with leading biomedical researchers, Brightseed discovered a powerful phytonutrient with the potential to improve metabolic health. This phytonutrient helps restore proper function of a central metabolic regulator, including maintaining healthy lipid and sugar levels in the bloodstream and key organs such as the liver, whose function is impaired by a poor diet. Brightseed will start clinical studies on this phytonutrient before the end of this year.

The impact of this discovery could be wide reaching and have profound implications for more than two billion people worldwide at elevated risk of chronic metabolic diseases. Elevated levels of fat in the liver (which are directly caused by chronic overeating) afflict between 25% and 30% of the global population. These individuals with fatty liver disease are 57% more likely to die prematurely and much more like to develop other debilitating metabolic diseases, including diabetes. The discovery of this phytonutrient is a glimpse into the positive change deeper nutritional understanding could bring.

Just as 1918 pandemic led to creation of the modern medicine industry, we now are at a similar tipping point with nutrition, on the precipice of developing a much more complete understanding of how plants are connected to human health.

The first step is improving our foundational knowledge. In the U.S., there is a broad-based effort among leading academic, non-profit and industry stakeholders to create a National Institute of Nutrition (NIN) to accelerate nutrition science and uncover the role of human nutrition in improving public health and reducing disease. The NIN, similar to institutes that exist in other countries, can support and incentivize higher-quality, more rigorous nutrition research at the molecular level. This research will provide a stronger foundation for nutrition recommendations and guidelines, which is essential to developing consensus in both the scientific and consumer communities.

The second step is a mindset shift. Modern food and agricultural systems have largely focused on - and solved - the problem of food insufficiency. However, preventable diet-driven chronic diseases have emerged instead. We need to pivot from merely increasing the supply of food to leveraging technologies that can help improve the nutritional quality of what we consume.

"We need to pivot from merely increasing the supply of food to leveraging technologies that can help improve the nutritional quality of what we consume."

Healthier food options can be the center of a new proactive health industry and provide the food industry the opportunity to make important contributions to health and longevity, while benefiting economically from the capture of existing healthcare investment that currently is directed to treating chronic disease. Our current treatment-focused healthcare system is increasingly unaffordable and poorly suited to addressing the needs of individuals at heightened risk of developing chronic diseases that are largely preventable through lifestyle modifications, especially those related to diet.

No changes will be possible without forging new collaborations between public and private entities. Through cooperation we can develop more nutritious options and greatly influence policy change. Partnerships are also how well create a more nourished world and maximize our impact.

For the first time, we have the tools to explore the plant kingdom at the molecular level and answer questions such as How does what we eat really affect us? or How can food become medicine?

Technology is exponentially improving our understanding of how plants are connected to health. Together, we can goal shift the healthcare model from one squarely focused on treatment of disease to one that promotes health and natural resilience.

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How AI is uncovering the 'dark matter of nutrition' - World Economic Forum