StemCell Therapy

If you think daily exercise and a healthy diet were the key to a long life, think again.

Scientists say that the secret to living more than 100 years comes down to a hardy immune system, thanks to an abundance of a particular infection-fighting white blood cell.

In a study coordinated by scientists at Japans RIKEN Center for Integrative Medical Sciences (IMS) and Keio University School of Medicine, researchers discovered that supercentenarians those aged over 110 years have an excess of cytotoxic CD4 T-cells.

These super immune system cells, according to the study published in Proceedings of the National Academy of Sciences (PNAS), are more aggressive and known to kill any damaged cell that crosses its path, such as virus-infected or cancer cells.

We believe that this type of cells, which are relatively uncommon in most individuals, even young, are useful for fighting against established tumors, and could be important for immunosurveillance, said Piero Carninci, deputy director of RIKEN, in a statement. This is exciting as it has given us new insights into how people who live very long lives are able to protect themselves from conditions such as infections and cancer.

Scientists noticed that most of Japans supercentenarians had managed to dodge illness most of their lives, leading them to believe their advanced age might have something to do with their extraordinary immune systems.

To find out, they pulled a total of 41,208 immune cell samples from seven supercentenarians, and 19,994 cells from younger individuals ages 50 to 89. They found that while both groups had about the same number of T-cells altogether, the supercentenarians had an excess of the unique cytotoxic CD4 T-cells.

This finding might help explain why so many centenarians will say that drinking booze regularly didnt stop them from reaching 100. Others, though, credit a life without the stress of marriage or children as helping them to outlast their peers.

Amparo Perez, 105, told The Post she doesnt regret never remarrying when her first husband died. No aggravation, she said, [is] the most important thing, not to have aggravation.

Caroline Binns, 101, would agree that husbands were only trouble. She told The Post last year, Id rather be left in peace, not in pieces.

Her friend, 101-year-old Lucille Watson, said dancing and cheesecake inspires her to get out of bed every morning: Lifes pleasures are meant to be enjoyed.

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110-year-olds live so long thanks to 'super' immune systems: study - New York Post

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Its that time of year time to break out the boots, light up the fireplace, and restock your over-the-counter cold medicine.

But maybe this year youre not so keen on the de rigueur drowsiness that comes with Tylenol Cold or the sugary aftertaste of Emergen-C. If so, consider the power of plants to up your immunity and help you hedge infections.

Yep, this is how to build a cold/flu season first aid kit with herbs.

Remedies made from herbs and plants are a modality full of powerful allies for your health and immunity, explains Sarah Corbett, Atlanta-based clinical herbalist at Rowan and Sage and science is starting to agree: Research is beginning to confirm the efficacy of folk medicines people have been using for hundreds of years, says Corbett.

Here are six easy herbal medicines you can add to your medicine cabinet (or fridge, as it may be) for a prevention booster, or as a healing aid.

Get the power combo

Herbs may give your immune system a little boost but nothing says wellness booster like the flu shot. Each year the flu shot is updated to help better fight viruses going around, because yes, the virus gets stronger and so should you. Get your flu shot.

Chances are, youve already tried elderberry in some form or another, as this deep-purple berry has definitely gone mainstream in the past few years.

Also called sambucus, elderberry is antifungal, antibacterial, and antimicrobial, so its good at knocking out any kind of crud youve got going on. Theres evidence that elderberry is effective at treating the flu, as well.

Its most commonly found as a syrup (it will make your kitchen smell divine if you DIY), but tinctures (a plant extract made with alcohol or glycerin), lozenges, and even gummies can work too.

Corbett advises taking this remedy once per day if youre trying to prevent sickness, and then much more frequently once youre already sick every few hours or so.

Elderberry is considered safe, but dont chug a whole bottle or anything like that a teaspoon to a tablespoon of syrup at a time will work. Keep syrups in the fridge, as they arent shelf-stable. If you have any autoimmune disorders, its probably best to stay away (because it stimulates the immune system).

Another well known immune booster is echinacea, aka coneflower. It works by stimulating the immune system to produce natural killer cells and other sickness-fighters.

A 2015 meta-analysis concluded that echinacea may benefit folks with low immune function the most, even reducing the risk for a cold up to 35 percent.

Corbett suggests echinacea is most effective used right when you start to feel that tickle at the back of your throat, rather than when a full blown sickness has already taken hold.

A tincture is the best way to take it, she says, but teas wont fail you either (especially since youll be hydrating your system in the meantime). Look for Echinacea angustifolia or a whole plant extract, because its the most chemically bioavailable (easily absorbed and used by the body).

Its important to note that if you have a ragweed allergy, you may also be sensitive to echinacea so if you feel any telltale allergy symptoms like itchiness, hives, or increased congestion, stop taking it immediately.

If you have an autoimmune disorder, skip echinacea.

Yes, ginger will soothe an upset stomach, but its also great for boosting your overall immunity during cold and flu season.

This versatile plant (which has been shown to be antimicrobial, antibiotic, and anti-inflammatory) lends its natural fire to many different uses sip on a ginger tea, head to the juice bar for a fresh ginger shot if youre feeling icky, or just add more ginger to your cooking.

Its pretty safe when used in cooking and remedies, but pregnant people shouldnt ingest more than 2 grams of dried ginger per day.

Garlics powers go well beyond making food taste delicious. Its thought to stimulate the immune system and boost the efficacy of white blood cells, though studies are inconclusive.

Garlic is really easy to use eat it every day to keep yourself feeling top notch. Up your garlic intake when youre actually sick, too. Make a super garlick-y soup (dont skimp on the bone broth, either), eat a couple of raw garlic cloves, roast a garlic bulb, or pack it into a jar of honey and let it sit for a few weeks to infuse.

Dietary doses of garlic are pretty safe. It would be difficult to take enough to harm you, but if youre on anti-clotting medications, be cautious. (And brush your teeth if you find yourself going high on the hog with raw garlic, too!)

This intense liquid, sometimes also called the Master Tonic, is kitchen medicine at its best: an intense mixture of garlic, ginger, onion, horseradish and hot peppers (plus any number of other immune-boosting ingredients like turmeric, or tasty ones like lemon or rosemary) marinated in apple cider vinegar.

Fire cider gets its efficacy from the communal power of these sinus-clearing, warming, infection-fighting plants plus an extra boost from the fermented ACV. And yes, this immune brew will burn (in a good way!) going down.

Its ridiculously easy to make, so whip up a batch and toss it on your salad every night, sprinkle it on rice or quinoa, or take a shot when you feel a cold coming on. If handcrafting isnt your jam, you should be able to find some from a local herbalist or at a natural food store.

Steer clear if you have GERD or a history of stomach ulcers.

Youve probably heard this wellness world buzzword in the last few years adaptogens but may not be clear on what exactly it means.

Essentially, adaptogens are therapeutic herbs that support the body in combating and adapting to stress. Theyre great to use for people who get sick often, says Corbett, or in times of heavy stress, travel, or extra exposure to pathogens (rather than for every day maintenance or prevention).

Ashwagandha, reishi (both of which stimulate your infection fighting lymphocytes, or white blood cells,) and holy basil (stimulates the immune system and also fights viruses) are all good choices for immune support, explains Corbett.

Buy reishi as a powder and mix it into anything youre eating or drinking its safe to take in small doses (like a scoop of powder or a squirt of tincture). Ditto for ashwagandha although steer clear of ashwagandha if youre taking thyroid hormones like Synthroid.

Holy basil can be made into an infusion and sweetened with honey (dont take it if youre pregnant, though, says Corbett). Research some other options, try a few, and see which ones work for you.

Corbett explains that many people think that herbal remedies dont work, but that its often because they arent using enough.

One cup of your basic grocery store cold-fighting tea blend per day isnt really going to do much to help your immune system flush out any offending bacteria, especially once youre already showing symptoms.

If you want to get the benefits from a tea, you have to steep it longer and/or use more herbal material (read: 2 or 3 tea bags per cup, or load everything up in a French press and let it really brew for 30 or more minutes).

The same goes for tinctures when suffering an acute condition, you need to be ingesting a full dropper (or whatever the guideline on the tincture bottle says) every few hours or so.

When in doubt about dosage (or even whether or not a certain herb will work with your body), consult a trained clinical herbalist, holistic physician, naturopath, or other trusted source regarding natural medicine.

And always see your healthcare provider or a pharmacist if youre planning to mix plant medicine with prescription medication.

Above all, tune in to your body before, during, and after any seasonal illnesses, says Corbett. The best medicine for illness is prevention.

While healthy looks different for everyone, there are solid steps you can prioritize this time of year to fight off winter nasties from taking root. You know the drill: sleep, fresh foods when possible, exercise and/or spending time outside, and staying hydrated. And if the cold does creep in, youve got plenty of plant allies to help you out.

No herb is a replacement for a healthy lifestyle, says Corbett. It can help, but it wont fix you. Your body has a vital intelligence that is equipped to send you messages about what it needs. Listen to it.

Carrie Murphy is a freelance health and wellness writer and certified birth doula in Albuquerque, New Mexico. Her work has appeared in or on ELLE, Womens Health, Glamour, Parents, and other outlets.

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6 Herbs to Keep Your Immune System in Fighting Shape - Greatist

A single dose of CD45-ADC, an investigational targeted therapy being developed to treat different types of autoimmune diseases, is enough to reset the normal function of the bodys immune system in a mouse model of multiple sclerosis (MS), and to delay onset of the disease.

Those findings were presented earlier this week in the poster Administration of a CD45 Antibody Drug Conjugate as a Novel, Targeted Approach to Achieve Immune System Reset: A Single Dose of CD45-targeted ADC Safely Conditions for Autologous Transplant and Ameliorates Disease in Multiple Models of Autoimmune Disease (abstract #120), at the American College of Rheumatology (ACR) Annual Meeting in Atlanta, Georgia.

CD45-ADC is an antibody-drug conjugate (ADC) being developed by Magenta Therapeutics in collaboration with Heidelberg Pharma. The medication works by delivering amanitin a toxic compound that belongs to a group of natural poisons produced by some species of mushrooms to overactive immune cells containing the CD45 protein on their surface. That destroys them and restores the normal function of the immune system. (Of note, the CD45 protein is typically found on immune cells and stem cells.)

For that reason, CD45-ADC is currently being explored as a new form of targeted therapy for several autoimmune diseases, including MS.

New findings presented at the ACR meeting showed that in mice withexperimental autoimmune encephalomyelitis(EAE, a mouse model of MS), a single dose of CD45-ADC was sufficient to eliminate overactive immune cells, and to restore the normal function of the animals immune systems.

Moreover, investigators reported that treatment with CD45-ADC, followed by a stem cell transplant to repopulate the animals bodies with healthy immune cells, delayed the disease onset and halted the progression of disease activity in EAE mice.

According to the research team, immune reset through stem cell transplant in which disease-causing cells are replaced by healthy cells to rebuild the immune system has been shown to induce durable remission in patients with autoimmune diseases, including MS.

Given the encouraging results in animal models, the team developed an anti-human CD45-ADC that cross-reacts with non-human primates (NHP). Substantial depletion of both lymphocytes [white blood cells] and hematopoietic [blood] stem cells (HSCs) was observed at well-tolerated doses, the researchers wrote.

CD45-ADC also is being tested in mice models of systemic sclerosis (scleroderma) and inflammatory arthritis, two other autoimmune diseases, and it has shown promising results.

Overall, the results suggest that targeted immune depletion with a single treatment of CD45-ADC may be sufficient for auto-HSCT [hematopoietic stem cell transplant], and allow re-establishment of immune tolerance, the team concluded.

Millions of patients worldwide live with debilitating autoimmune diseases, with no options for curative therapy. Magenta is developing targeted medicines, such as CD45-ADC, to enable more patients with autoimmune diseases to undergo a one-time, curative immune reset, John Davis, MD, MPH, chief medical officer of Magenta, said in a press release:

The data presented at ACR provide important proof of concept for our immune reset platform across a broad range of diseases, including multiple sclerosis and systemic sclerosis, Davis said. We expect to declare a development candidate and progress this medicine into IND [investigational new drug]-enabling studies next year as we work to allow more patients to live their lives without autoimmune disease.

Magenta also announced it has exercised its right to become the exclusive holder of global development and marketing rights of any ADC targeting CD45 based on Heidelberg Pharmas proprietary amanitin toxin-linker platform technology.

Under the terms of the collaboration agreement established between Magenta and Heidelberg Pharma in 2018, Magenta is eligible to use Heidelberg Pharmas proprietary amanitin technology to generate up to four different ADC compounds based on an exclusive target of choice. In turn, Heidelberg Pharma is eligible to receive milestone payments.

Joana is currently completing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. She also holds a BSc in Biology and an MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells cells that make up the lining of blood vessels found in the umbilical cord of newborns.

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Patrcia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.

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Single Dose of CD45-ADC Resets the Immune System in Mice with MS - Multiple Sclerosis News Today

The following is an article of faith for many who refuse to have their children vaccinated against childhood diseases: That when healthy children get and recover from an infection naturally, their immune systems come out stronger.

However, when it comes to measles, the opposite is true, according to two studies published on Oct 31, 2019.

In a group of 77 Dutch schoolchildren whose parents declined to vaccinate them on religious grounds, the new research documents several ways in which infection with measles can hobble a childs immune function for months, or even years, after that child has recovered from her bout with the virus.

The effect was mild in some of the children.

But in roughly 16% of those who suffered an active measles infection, the result was a severe case of immune amnesia.

In those children, a genetic census of antibodies immune proteins that recognise and destroy invading microbes showed that they had lost at least some immunity to more than 40% of common childhood diseases.

Measles appeared to have stripped away immune protections these children had built over years of exposure to diseases and germs.

Measuring the same childrens immune memory 40 days after measles infection, a second team found significant shrinkage in their stores of B-cells, which fight disease by killing infected cells and spawning legions of antibodies to confront viral invaders in the blood.

For weeks after the unvaccinated children had recovered from measles, their depleted stocks of B-cells signalled a loss of memory for past infections and of strength to mount a defence against new infections.

For some, the damage appeared to be even more extensive.

In two of 19 measles-infected children tested, the machinery that supplies the immune system with new disease-targeting cells was profoundly disrupted, raising questions about whether they would fully recover their previous strength.

The measles virus is like a car accident for your immune system, said Harvard University geneticist Stephen Elledge, one of the papers co-authors.

An unvaccinated child who weathers the measles may emerge only slightly the worse from such a crash.

Or he might sustain an injury from which it takes months or years to recover.

For parents, the studies implications are clear, Elledge added.

We know how to prevent injuries in car accidents by wearing seatbelts.

The measles, mumps and rubella (MMR) vaccine is like a seatbelt for your immune system, and parents should buckle their kids up.

The studies were published in the Science and Science Immunology journals respectively.

One in six children who are infected with measles will find themselves more vulnerable to other common childhood illnesses after recovering from measles. PP

A concurrent fall

The research sheds new light on the biological basis for a mysterious phenomenon long recognised by doctors.

After children recover from the measles hallmark rash and fevers, they are highly unlikely to fall ill with it again.

But for two to three years following infection, patients remain unusually vulnerable to catching or developing other infections, from viruses like the common cold and influenza to potentially deadly bacterial infections that can cause pneumonia or swelling in the brain.

Researchers reckon that before the introduction of a measles vaccine in 1963, as many as half of childhood deaths from infectious diseases were linked to measles or the immunosuppression that follows.

In that period, this most contagious of viruses infected over 95% of all children and directly caused over four million deaths a year.

But in places where vaccine campaigns have virtually eliminated outbreaks, public health officials have documented unexpectedly large reductions in childhood deaths from other diseases.

Preventing infection with measles was clearly saving kids from succumbing to other bugs as well, experts say.

The mystery of how measles sets kids up for poorer health might have lost its urgency if global vaccine campaigns were expanding without pushback.

But they are not.

Every year, more than seven million people, mostly in poor countries, are still infected and roughly 100,000 die of measles.

And in recent years, an uptick of vaccine refusal in the United States and Europe has reversed decades of rising vaccination rates in the worlds most affluent countries.

In the first three months of 2019, parents reluctance to have their children vaccinated helped drive worldwide cases of measles up 300% over cases reported in the first quarter of 2018, according to the World Health Organization (WHO).

The US declared measles eliminated in 2000. But pockets of anti-vaxxers have allowed it to gain a foothold in communities across the nation.

Between Jan 1 and Oct 1, there have been 22 US outbreaks of measles.

Of the 1,250 cases documented in 31 American states during that period, 89% of patients were unvaccinated or did not know their vaccination status.

Not since 1992 has the tally of measles cases in the US reached so high.

While none have died, 119 required hospitalisation and 60 developed pneumonia. One patient suffered encephalitis, a life-threatening swelling of the brain.

Measles is not a trivial disease and these findings add evidence that its important to vaccinate your kids against it, said US National Institute of Allergy and Infectious Diseases director Dr Anthony Fauci.

Theres scientific proof here that not only is measles itself a serious disease; it can have consequences of suppressing the bodys defence mechanisms for a year or more.

Decreased immunity

The measles virus is somehow related to a loss of over 40% of antibodies for common childhood diseases after it infects a child. 123rf.com

The two new studies human subjects belong to part of the vaccine-refusal movement with deep roots.

Members of a Dutch sect of orthodox Protestants, they form a closed community within Dutch society, with their own churches, schools, newspapers and political party.

Since the 19th century, when vaccination campaigns gained steam and drew protests throughout the US and Europe, these Dutch Protestants have declined vaccination.

Their opposition rests on passages in the Bible that call on believers to trust in divine providence for protection.

In the US, those opposed to vaccination on religious grounds have remained a steady presence.

But discredited claims that the MMR vaccine is a cause of autism have driven down vaccination rates in pockets across California, New York and elsewhere, and prompted vaccine reluctance among many parents.

Most recently, false claims circulating among members of New York Citys Orthodox Jewish community that MMR vaccine contains monkey, rat and pig DNA, and contravenes kosher dietary requirements have figured prominently in recent outbreaks.

More than three-quarters of measles cases in the US this year have been in New York.

The Dutch schoolchildren in the new studies, who ranged in age from four to 17, were followed for only up to eight weeks after their infections.

But each team also conducted animal studies that found measles affects immunity in real and enduring ways.

One of the teams, based in the Netherlands and the United Kingdom, used ferrets to demonstrate post-measles vulnerability to flu.

Even after they had been immunised against influenza, ferrets who were infected with measles and then exposed to a flu virus, got much sicker than ferrets who had not had measles.

A second team, led by Harvard epidemiologist Michael Mina and Elledge, assessed the array of antibodies in four rhesus macaque monkeys before and after measles infection, and found that for five months after their infections cleared, the monkeys sustained a loss of immunity to an average of 40% to 60% of diseases.

Mina and Elledge said their work offers new insights into the longstanding mystery of how measles seems to put children at increased risk of infections.

And they added, it underscores the outsize value of a simple protective step: having a child vaccinated with the MMR vaccine just after her first birthday and again between the ages of four and six.

Such evidence may not sway the most committed vaccine opponents, Mina said, but most people are really trying to do whats right for their kids.

Even when those parents are inclined to believe their child could weather a bout of rash and fevers, he added, telling them that for the next few years, theyre going to have to look over their kids shoulder at diseases he might get sick from, that makes this amnesia effect quite a bit more scary. Los Angeles Times/Tribune News Service

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Measles infection causes 'amnesia' of the immune system - The Star Online

By Gege Li

The keto diet involves foods that are high in fat and low in carbohydrates

Ditching carbohydrates and eating lots of fat may give some protection against the flu. Feeding mice the so-called keto diet seems to boost certain immune cells, which may be responsible for the effect.

The keto diet forces the body to burn fat for energy, which can help with weight loss, and people may get flu-like symptoms known as the keto flu as their body adapts to so little carbohydrate. The keto diet has also been linked to improved heart health and control of blood sugar in diabetes, but much of the evidence is conflicting.

Akiko Iwasaki at Yale School of Medicine and colleagues previously found that the keto diet reduced inflammation in mice with gout. Because inflammation is common to both gout and flu, the team thought the keto diet could similarly deal with flu-related inflammation, which can severely damage the lungs.

To put this theory to the test, the team fed mice infected with influenza A the most serious type of the virus either a keto or standard diet for a week before infection. After four days, all seven of the mice fed a standard diet succumbed to the infection, compared to only five out of the 10 mice on the keto diet. These keto diet mice also didnt lose as much weight, which is usually a clear sign of flu infection in animals.

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The team found that the keto diet amped up the numbers of a specific type of T cell key players in the bodys immune response found in the lungs. Boosting these T cells dampened the sensitivity of cells lining the lungs to infection and increased mucus production.

It seems that this extra mucus is important for protecting the mice, says Iwasaki, because it traps the flu virus to stop it spreading. It still isnt clear what these T cells do outside of this study though, she says.

Although mouse and human metabolisms differ, the finding could mean that people get a similar protection from influenza when on the keto diet.

We already knew of a link between diet and immunity, says John Tregoning at Imperial College London, who wasnt involved in the work. Eating foods rich in vitamin C, for example, is known to strengthen our immune system. Switching to a keto diet may help boost the immune system so that it is better programmed to fight off the infection, says Tregoning.

Journal reference: Science Immunology, DOI: 10.1126/sciimmunol.aav2026

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Eating a keto diet may give some protection against the flu - New Scientist News

AsianScientist (Nov. 18, 2019) ASLAN Pharmaceuticals, a clinical-stage oncology and immunology focused biopharma company, has established a joint venture with Korean pharmaceutical company Bukwang Pharmaceutical to develop preclinical aryl hydrocarbon receptor (AhR) antagonists.

AhR is a druggable protein that acts as a master regulator of the immune system. When kynurenine, a molecule produced in the tumor microenvironment, binds to AhR on a group of immune cells known as T-cells, the anti-tumor activity of T-cells is suppressed. Hence, by targeting AhR, scientists hope to prevent the suppression of T-cell activity, which in turn allows for stronger immune responses that destroy tumors.

Under the terms of the agreement, ASLAN will transfer the global rights to all of the assets related to AhR technology into the joint venture, manifested as the independent company JAGUAHR Therapeutics and based in Singapore. Bukwang will invest US$5 million in JAGUAHR in two tranches to fund the development of the assets, identify a lead development compound and file an investigational new drug application.

The launch of JAGUAHR Therapeutics is an important step by ASLAN to realize the value of our early stage assets and advance the development of our AhR antagonist technology at a time when focus is shifting towards AhR antagonists as a hot new area in immune-oncology, said Dr. Carl Firth, CEO of ASLAN Pharmaceuticals.

Bukwang has a strong track record of achievement in the pharma business, and creating this spinout together allows both companies to quickly progress these exciting compounds and potentially provide novel clinical assets to enrich the ASLAN pipeline. We look forward to working with the Bukwang team as we focus on identifying JAGUAHRs first drug candidate, he added.

Source: Aslan Pharmaceuticals; Photo: Shutterstock.Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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ASLAN And Bukwang Team Up To Develop Immune-Oncology Drugs - Asian Scientist Magazine

Study design and period

The trial is a single center, two-armed phase III study. The trial has been registered at http://www.clinicaltrials.gov (NCT03201926). Patients will be recruited by the Pancreatobiliary Cancer Clinic, Gangnam Severance Hospital, Yonsei University College of Medicine. The expected total duration of patient accrual is 2years and 6months and the follow-up period is 6months.

The primary endpoint is to evaluate body cell mass index at 2months postoperatively. Secondary endpoints include other body composition changes as well as nutrition index and immune function.

Patients scheduled for surgery with pancreatobiliary disease and liver cancer (HCC, CCC, and metastatic liver cancer)

Karnofsky performance status 70

Patients who provide informed consent

Patients who underwent palliative surgery

Patients with uncontrolled preoperative conditions

Previous history of surgery affecting nutritional status (ex, gastrectomy, colectomy, etc)

Pregnant and lactating women

Patients with an allergy to mealworms

The output of the sample size will be based on an independent two-sample t test. It is expected that there will be a difference in body cell mass between the standard meal group (control) and the group ingesting the mealworms. Assuming an alpha value of 0.05 and 1- (power) of 0.8, 75 samples will need to be obtained for each group; considering the dropout rate of 10%, 84 samples will need to be obtained for each group. The total of the two groups is 168. The primary endpoint will be the number of subjects and body cell mass. A comparison will then be made between the two groups at 2months. A subgroup analysis of pancreatobiliary and liver disease will also be performed as a secondary endpoint. Patients with pancreatobiliary and liver disease in our clinic have a 2:1 ratio. Therefore, the 168 patients were divided into two groups: one with 112 patients and the other with 56 patients. Patients with pancreaticobiliary disease (Group A & B) and liver (Group C) disease were assigned through stratified randomization. Pancreatobiliary disease group is divided into enteral feeding group(Group A) and non enteral feeding group.(Group B).

All patients who are potential candidates for hepatopancreatobiliary surgery will undergo a standard evaluation that will include contrast-enhanced computed tomography (CT), endoluminal ultrasound (EUS), magnetic resonance imaging (MRI), and positron emission tomography (PET-CT), which will be discussed at the preoperative conference.

Patients recommended for major hepatopancreatobiliary surgery (such as a liver resection, pancreaticoduodenectomy, or total/distal pancreatectomy) will be contacted and provided with a participant information sheet. Patients will be divided into three groups according to the type of surgery.

Patients receiving dietary supplementation with mealworms after their pancreatectomy, bile duct resection and hepatectomy will be given the mealworms during their hospitalization period and for another 2months after discharge. The patients in group A will undergo enteral feeding after surgery (for those who undergo a pancreaticoduodenectomy, nutrients will be administered by an enteral feeding tube for early feeding while securing the pancreatojejunostomy). A feeding nasojejunal tube will be placed for patients in the enteral feeding group. Enteral feeding (Newcare 300 RTH, Daesang, Korea) will start within 24h postoperatively at a rate of 20mL/h. The velocity will be progressively increased by 20mL/d until reaching the full nutritional goal (25kcal/kg). Enteral feeding will be delivered by an infusion pump for 18h/day with 6h of rest.

On postoperative day 7, abdominal and pelvic CT scans will be obtained, and if there are no complications, we will then start patients on a clear liquid diet for 1day. In addition, the patients will be permitted to have a full liquid diet for 2days and then a soft diet for 3days following the liquid diet.

The patients of group B will undergo oral feeding 2days after the surgery. (distal pancreatectomy, total pancreatectomy and bile duct resection) We will start patients clear liquid diet for 1day. The patients will be permitted to have a full liquid diet for 2days and soft diet for 3days following the liquid diet.

The patients of group C will undergo oral feeding 2days after surgery (which includes liver resections). We will then start the patients on a clear liquid diet for 1day. In addition, the patients will be permitted to have a full liquid diet for 2days and soft diet for 3days following the liquid diet. The mealworm powder include 3g of carbohydrate, 14.4g of protein and 11g of fat, 163kcal per 30g. (Table 1) As a result of a nutritional analysis of mealworm powder, 10.28g of carbohydrate, 48.26g of protein and 35.81g of fat were found per 100g. In particular, the protein includes essential amino acids as well as many unsaturated fatty acids ranging from 76 to 80% of the total fatty acids. In addition, iron and calcium and other minerals were found (Table 2).

Patients receiving dietary supplementation with grainpowder after pancreatectomy and hepatectomy will be given grainpowder for their hospitalization period and 2months after discharge. The grainpowder include 23g of carbohydrate, 2.9g of protein and 0.5g of fat, 106kcal per 30g. Group A will receive the grainpowder on postoperative day 7. And group B and C will receive grainpowder in the same dose as trial groups mealworms at the start of diet at postoperative 2days (Table 3).

The primary outcome is the body cell mass index as measured by body composition (Inbody S-10 (Biospace, Seoul, Korea)). The secondary outcome measures are as follows: nutritional index (weight, soft lean mass, fat free mass, fat mass, PG-SGA [Scored Patient-Generated Subjective Global Assessment]) and immune function test (that assesses T cells, B cells, cytokines). We will confirm changes in immune cells through FACS (fluorescence-activated cell sorting). Based on the immune assay using blood samples from patients, we will identify changes in several cytokines.

Once the patients surgery is confirmed, the research staff will give the study staff a list of the patients. After determining the suitability of the patient, the study staff will assign the patient to the test or control group in a randomized sequence in the order in which they are enrolled. In addition, they will be assigned in a double-blinded manner.

The researchers will select patients after obtaining consent. Randomization will take place via an allocation randomization system 2days before the surgery, which will be directed by our department. Patients will be randomized to one of the treatment groups in a 1:1 ratio. After consent for study enrollment is obtained, the randomization process will be applied to identify the next allotment. The surgeons will be blind to the allotment throughout the enrollment process.

Patients and all team members will be blinded to the intervention. Adverse event (AE) and serious adverse event (SAE) need to be reported as soon as they are noted. This will not have any impact on the endpoint assessment of the patient.

The amount of food consumed by the patient daily will be assessed as a diary entry. The researcher collects the bags left over from the patients at the outpatient clinic. Individual participant medical information obtained as a result of this study is considered confidential and disclosure to third parties is prohibited. Blood samples transferred to the laboratory of Gangnam Severance Hospital will be identifiable by unique trial numbers only. Results related to nutrient indicators (Inbody, PG-SGA) will be managed by a Gangnam Severance Nutrition Team. The blood sample associated with the immune function test will be transferred to the lab of the study staff in Gangnam Severance Hospital, which will then undergo FACS (Fluorescence-activated cell sorting).

If patients wish to voluntarily withdraw from the study, the patient will be asked if they would be given medical care until any AE symptoms resolve or the patients condition becomes stable.

Patients can quit the trial at any point without the need to give reasons for their decisions. If voluntary withdrawal occurs prior to diet intervention, the patient will not be randomized, and no more trial data will be collected for that patient. Patients can also withdraw from the trial following diet intervention.

All data will be entered into a single Microsoft Excel spreadsheet with participants identified only by their unique subject number. All entries will be double-checked by another member of the research team. Statistical analysis will be performed using IBM SPSS version 21.0 (IBM Corp; released 2012. IBM SPSS Statistics for Windows Version 21.0. Armonk, NY, USA). The mean difference in nutrient intakes, changes in body measurements, changes in body composition, and PG-SGA scores will be calculated using the Wilcoxon signed rank test and the Mann Whitney test.

The research team is responsible for monitoring the study. At 1week after discharge, the participants are asked whether they are willing to continue ingesting the mealworm. Every 2weeks after the patients visit their outpatient clinic, the monitoring researcher will check whether they are taking the mealworm regularly. The research team is also responsible for systematically reviewing the causes of withdrawal from the study. Assessment of these changes will be determined 2months after surgery (Table 4).

The study protocol was approved by the institutional review board at Gangnam Severance Hospital, Yonsei University of Korea (32017-0077). The study complies with the Declaration of Helsinki and the principles of Good Clinical Practice.

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Clinical application of invalid foods using mealworms and evaluation of nutrition status and immune function: a study protocol for a randomized,...

The secret to living past 100 could lie in your immune system, suggests a new study.

In a study recently publishedin Proceedings of the National Academy of Sciences (PNAS), scientists found that supercentenarians those who are 110 years of age or older have an overabundance of a certain type of disease-fighting cell within their immune systems, possibly explaining their longevity.

To come to this conclusion, researchers looked at the circulating immune cells from supercentenarians and controls aged 50 to 89. About 41,208 immune cell samples were taken from seven supercentenarians, while 19,993 cells were collected from the five controls.

The study found that while the supercentenarians and controls had roughly the same amount of T-cells overall, the former group had an excess amount of one particular subset of T-cells called cytotoxic CD4 T-cells. These cells, according to a news releaseon the findings, are aggressive and quickly destroy cancer and infection-causing cells.

In some cases, the cytotoxic CD4 T-cells accounted for 80 percent of the supercentenarians T-cells, while only 10 to 20 percent of the T-cells in the controls were cytotoxic CD4 T-cells, according to the research, which wasconducted by the RIKEN Center for Integrative Medical Science (IMS) and Keio University School of Medicine in Japan.

The super immune system cells are likely not a marker of youth, but rather a special characteristic of the supercentenarians, the researchers wrote. The cytotoxic CD4 T-cells are likely the offspring of a sole ancestor cell.

We believe that this type of cells, which are relatively uncommon in most individuals, even young, are useful for fighting against established tumors, and could be important for immunosurveillance, said Piero Carninci, the deputy director of RIKEN, in a statement. This is exciting as it has given us new insights into how people who live very long lives are able to protect themselves from conditions such as infections and cancer."

Gallery: 100 Ways to Live to 100 (Provided by Best Life)

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Study: The secret of living to 110 - msnNOW

The holiday season is coming up quick, and along with dancing sugar plums and a strong dose of seasonal cheer can come some uninvited guests, including the common cold and flu bug. So, what can you do to give your body the best fighting chance to avoid getting sick this holiday season? Sleigh Family Chiropractic offers the following tips to help boost your immunity system with the goal to remain among the healthy:

Decrease Sugar Intake and Exercise: Avoiding too much sugar (especially at all those holiday parties) can be a bit of trick. Over-consumption can substantially decrease the immune system's ability to attack viruses and bacteria for up to eight hours after you enjoy that delicious piece of pie. Meanwhile, getting just 30 minutes of exercise (maybe before or after the party) each day can help the immune system to remain strong against infection.

Reduce Your Stress: The holidays can create a variety of stress for some, which is a natural immune depressor. Different ways to reduce stress include utilizing deep breathing exercises, meditation and yoga, or simply scheduling some time for yourself. Whether it's a day at the salon for a mani/pedi, a massage, spending time with your favorite friends, or taking a peaceful (and potentially brisk) walk in the park, take the steps that will help you keep it stress-free over the holidays.

Get More Sleep: More sleep simply makes sense it allows your body to recharge and take on all the challenges of the day. Ashwaghanda is an herb that has been shown to reduce anxiety and encourage calm and relaxation. It is made up of phytochemicals called withanolides that are believed to reduce the body's stress response and help to achieve restful sleep. Other tips include having a consistent wake up and bedtime routine and avoid 'blue light' activities such as using a computer or a cell phone up to two hours before going to bed. Keep your office out of the bedroom; allow it to be a sanctuary away from technology that invites rest and relaxation.

Eat Foods High in Vitamins C & D or Take Supplements:

Try Elderberry Syrup: The berries and flowers of elder trees and plants (known as Sambucus nigra) contain antioxidants and vitamins that have shown promise in boosting the immune system over centuries. The use of these trees and plants, and the syrup that comes from them, dates to 400 B.C. and Hippocrates, who called the elder tree his 'medicine chest'. Elderberry syrup has also been used to reduce stress and inflammation, as well as protect the heart.

Wash Your Hands Frequently: Washing your hands often, with soap, is one of the easiest ways to avoid spreading germs to others and yourself. Germs can be spread through contact with your eyes, nose and mouth, and can be transmitted through a variety of surfaces. Remember to wash your hands often to reduce the spread of sickness, especially over the holidays so you can enjoy all the festivities.

Katie and Quintin Sleigh, along with the entire Sleigh Family Chiropractic team wish you and yours a very happy - and healthy - holiday season!

About Sleigh Family Chiropractic

Drs Katie and Quintin Sleigh own and operate Sleigh Family Chiropractic, a family wellness clinic located at 3285 N. Arlington Heights Road in Arlington Heights. For more information, call 847-788-0880 or visit SleighFamilyChiropractic.com.

Resources/Reference Information:

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Immunity Boost Tips to Help You Stay Healthy Over the Holidays - Patch.com

A new project has shown how a one-off injection can halt peanut allergies for up to six weeks.

Scientists from Stanford University School of Medicine carried out a small pilot study involving an injectable antibody treatment that allows people with severe peanut allergies to eat a peanut with no trouble at least two weeks later.

Allergiesare simply a misguided overreaction by the bodys immune system. We typically experience an immune response to a foreign substance or pathogen that could cause harm to the body. With allergies, however, the response is fired up to substances that arent actually harmful to your body, such as the protein in peanuts, a rogue piece of pollen, or pet hair.

The only currently available treatment, oral immunotherapy, involves the patient eating minuscule but escalating doses of the allergen over the course of months, eventually desensitizing their immune system to the substancein question.

The new treatment takes a much more direct approach. Reported in JCI Insight, the treatment called etokimab works to interfere with an immune-signaling molecule known as interleukin-33 which triggers the chain of events that amount to a full-blown immune system response.

By inhibiting IL-33, we potentially inhibit features of all allergies, which is promising, senior author Kari Nadeau, professor of medicine and of pediatrics at Stanford, said in astatement.

Whats best, and quite surprising, is how long the treatment lasts. The double-blind study involved 20 participants with severe peanut allergies 15 received a single etokimab injection and five were given a placebo. Up to 15 days later, 73 percent of the etokimab group was able to eat a nuts worth of peanut protein without any allergic reaction. By day 45, 57 percent of them were able to.

The small study only involved 20 participants, but its success holds real hope for the 32 million Americans who suffer from potentially deadly food allergies. Next up, the researchers are looking to carry out another study with more participants and take a deeper look at the mechanisms involved.

Perhaps most promising of all, the treatment could theoretically be used to protect against a whole host of allergens, not just peanuts.

Whats great about this treatment as an option for food allergies is that people did not have to eat the food to get desensitized, Nadeau added. Although this is still in the experimental stages, were delivering on the hope of testing a drug that wont be for one food allergy but for many, and for other allergic diseases, too.

Cases of food allergies, along with eczema and hay fever, have risen rapidly in the developed world over the past few decades. There are thought to be a number of explanations for this, ranging from adecreased exposure topathogens to a change in diet. Regardless, despite this increase,allergies remain surrounded by myth and misinformation. Here are some common myths about allergiesthat you should be aware of.

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A Single Injection Stops Peanut Allergies For Up To Six Weeks - IFLScience

Immunotherapy is a form of cancer treatment that is now being used to treat many different types of cancer. However, stimulating the immune system through activated t-cells may result in T-cells acting upon other body systems or organs, unable to distinguish the cancer, causing inflammation and other adverse events (AEs).

Beth Eaby-Sandy, nurse practitioner at the Abramson Cancer Center, spoke at theCUREpatient-focused sessions held in tandem with theAnnual New York Lung Cancers Symposiumabout immunotherapy AE management. Your body is in a constant state of self-tolerance, she said. These drugs that we use do 1 of 2 things. We are either trying to stimulate the immune system to kill cancer [or] were trying to stop cancer from alluding the immune system.

Any body system or organ can become inflamed or damaged by the overactivity of T-cells. Some types of immunotherapy may result in severe inflammation-related reactions. If patients are experiencing any AEs from immunotherapy, they should be seen and treated immediately.

Hypothyroidism is one of the most common AEs caused byimmunotherapy. Once immunotherapy disables the thyroid gland, it is permanent, and the patient will not regain thyroid function and must then be on levothyroxine for life. Patients may also experience hyperthyroidism, though less common, causing a patient to over-secrete thyroxine and can lead to hypothyroidism if prolonged.

Fatigue is commonly reported in patients who receive immunotherapy, though it is unclear as to what causes it. Another common AE of immunotherapy can be arthritis, induced by T-cells attacking the joints. Low-dose steroids or other drugs traditionally used to manage arthritis are recommended for patients. Nausea and diarrhea (without colitis) have been reported, though not necessarily known why.

More AEs include:

Lowering of blood counts is not commonly seen in immunotherapy as it is in chemotherapy. Hair loss should also not occur, though hair thinning may.

Dont be afraid of immunotherapy! The majority of these patients do very, very well for often long periods of time, so its not something to be afraid of. We can usually manage these side effects very easily, Eaby-Sandy said.

Reference:

Eaby-Sandy. Immunotherapy Adverse Effect Management. Presented at:CUREpatient-focused sessions held in tandem with theAnnual New York Lung Cancers Symposium; November 9, 2019; New York, New York.

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Adverse Events To Be Aware of With Immunotherapy Treatment in Lung Cancer - Cancer Network

MENLO PARK, Calif.--(BUSINESS WIRE)--Personalis, Inc. (Nasdaq: PSNL), a leader in advanced genomics for cancer, today announced that the company will participate in the AACR Tumor Immunology and Immunotherapy conference at the Boston Marriott Copley Place in Boston, MA, November 17-20, including poster presentations on November 18th and 19th.

The company will showcase ImmunoID NeXT, the first platform to enable comprehensive analysis of both a tumor and its immune microenvironment from a single sample. ImmunoID NeXT can be used to investigate the key tumor- and immune-related areas of cancer biology, consolidating multiple oncology biomarker assays into one and maximizing the biological information that can be generated from a precious tumor specimen.

Following is a list of abstracts that will be presented at the meeting.

Scientific Poster Presentations

Poster Number

Title & Presenter

Day & Time

Location

A19

HLA allele-specific loss of heterozygosity detectionusing augmented exome capture approach

Presenter: Rachel Marty Pyke, Ph.D.

November 18:12:30 PM 3:00 PM

Back Bay

B18

Exome scale liquid biopsy monitoring of putativeneoantigens and genomic biomarkers in patientson anti-PD-1 therapy in squamous cell carcinoma ofthe head and neck

Presenter: Charles Abbott, Ph.D.

November 19:4:30 PM 7:00 PM

Back Bay

Personalis will also be exhibiting during the conference (Exhibit # 10). Representatives will be available to answer questions about the companys cancer immunogenomics services.

About Personalis, Inc.

Personalis, Inc. is a growing cancer genomics company transforming the development of next-generation therapies by providing more comprehensive molecular data about each patients cancer and immune response. The companys NeXT Platform is designed to adapt to the complex and evolving understanding of cancer, providing its biopharmaceutical customers with information on all of the approximately 20,000 human genes, together with the immune system, from a single tissue sample. Personalis also provides genomic information to the VA Million Veterans Program as part of their goal to sequence over a million veteran genomes. The Personalis Clinical Laboratory is GxP aligned as well as CLIA88-certified and CAP-accredited. For more information, please visit http://www.personalis.com and follow Personalis on Twitter (@PersonalisInc).

Link:
Personalis, Inc. to Present New Data at the AACR Tumor Immunology and Immunotherapy Conference - Business Wire

According to results of a study presented at the Society of Immunotherapy for Cancer (SITC) Annual Meeting 2019 in National Harbor, Maryland, a next-generation sequencing (NGS)-based approach was capable of simultaneously characterizing all 7 T- and B-cell receptor chains, and also provided potential predictors of treatment benefit in patients with renal cell carcinoma (RCC).

An extensive repertoire of T-celland B-cell populations that expresses a wide range of antigen-specificreceptors are at the heart of the adaptive immune system. More specifically, T-and B-cell receptor diversity is created through random recombination ofvariable (V), diversity (D), and joining (J) gene segments, or V and J genesegments alone. Hence, at any given point in time, the T-cell and B-cellrepertoire in a single individual is represented by a huge number of differentT- and B-cell clones or clonotypes.

Recently, high-throughput NGS hasbeen used to profile the diversity of the T-cell and B-cell repertoire inindividuals. One approach to this process involves RNA-based multiplexpolymerase chain reaction (PCR) amplification of V-D-J or V-J gene segments,followed by high-throughput sequencing of the PCR amplicons, and subsequentbioinformatic interpretation of the reads obtained through NGS.

In thisstudy, a novel quantitative PCR-based NGS technique was reported to allow forthe simultaneous characterization of RNA associated with the loci of all 7 T-and B-cell receptors (ie, the alpha, beta, gamma, and delta chains of theT-cell receptor; and immunoglobulin (Ig)-K and Ig-L of the B-cell receptor)collected from both peripheral blood mononuclear cells (PBMCs) andformalin-fixed paraffin-embedded (FFPE) specimens from patients undergoingtreatment for RCC.

Furthermore,this process was carried out as single reaction that circumvented the problemof PCR dimer artifacts.

Results of this study suggestedthat pretreatment diversity in T-cell receptor alpha and beta chains, as wellas the B-cell to T-cell expression ratio, may be useful predictors of treatmentresponse in patients with RCC.

Reference

Depinet M, Pan W, Wu S, et al. All-in-One, quantitative immune repertoire profiling of PBMC and FFPE for renal cancer treatment evaluation. Presented at the Society for Immunology of Cancer (SITC) Annual Meeting 2019. November 6-10, 2019. National Harbor, MD. Abstract P87.

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High-Throughput Multichain Immune Repertoire Sequencing for Prediction of Treatment Response in Renal Cell Carcinoma - Cancer Therapy Advisor

For most patients,sudden cardiac death iscompletely unexpected, according toDr. Amit Khera, a cardiologist at Massachusetts General Hospital.

Its always particularly devastating because many dont have prior symptoms. Their first symptom is actually dropping dead, Khera said. The question is can we find these people before something really bad happens?

Many scientists, including Khera, theorizedthat one way to find people who might suffer these sudden cardiac deaths fatal events related to an abrupt cardiovascular failure could betheir genetics.

We always had a hunch that maybe there was something in their DNA that predisposed them to this tragedy, he said.

Now, he and his colleagues believe theyve found 14 different gene variants, spread across seven genes that may put their carriers at greater risk for sudden heart death.

The researchers made this discovery by sequencingthe genes of 600 people who died from sudden cardiac death and600 people of the same age whowere healthy. Khera said they focused on 49 genesalreadyknown to be important for cardiovascular disease.

These genes contribute to any of the four major causes [for sudden cardiac death], he said. Sometimes its a weak heart and the pumping function is not quite right. The second is a heart attack. The third is a problem with the hearts rhythm. The last is a tear in a major blood vessel.

After a geneticist on the team analyzed the genetic data, Khera said 14 different versions of 7 genes stood out.

These 14 variants were found in 15 people. Whats really striking is that all 15 people were sudden cardiac death cases and zero were [healthy], he explained.

The team reported their findings Saturday in the Journal of the American College of Cardiology.

After identifying the specific gene variants, theresearchers looked ata larger database of 4,000 individuals. They found that about 1% of the population without a history of heart disease carries them.

Its a really small percent of people, but an important percent," said Khera. "These people are predisposed to sudden cardiac death, and if we can find them then we have tools to prevent disease onset.

Carrying one of these gene variants doesn't mean a person is certain to suffer from sudden cardiac death. But over a period of 15 years, Kherasaid, peoplewho carry at least one of the 14 gene variantsare three times more likely to succumb tosudden cardiac death.

In most cases, doctors saysudden cardiac death arises from preventable causes.

Most of the gene variations underlying [sudden cardiac death] are related to the electrical rhythm of the heart going chaotic or haywire," said Dr. Eric Topol, vice president of Scripps Research and a cardiologist who did not work on the study.

"There are many ways you can prevent this occurrence if you know a person has a high risk mutation, Topol said. Medications or a device like a defibrillator or pacemaker can fix the underlying problem.

There are likely many more mutations that increase the risk for sudden cardiac death.

The more we find of these, the more confident we are that they are the real deal, the better we will, in the future, be at preventing these catastrophes, Topol said. So, I think this is really important work.

And not every sudden cardiac death strikes healthy individuals with no previous history of heart disease, Khera added.

Of course, important lifestyle factors play a role, like smoking over the course of a lifetime or not well controlled blood pressure, he said.

But often, families and friends of those who die from sudden cardiac death dont get a reason for why it happened.

The DNA can provide an explanation as to why this happened, Khera said. And even more importantly, this persons family members may also have the gene variant, and if they know about it then they can take preventative measures.

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Knowing If You Have One Of These 14 Genetic Mutations May Help Prevent Sudden Cardiac Death - WBUR

Mining the rich uncharted territory of the genome, or genetic material of a cancer cell, has yielded gold for Princess Margaret Cancer Centre scientists: new protein targets for drug development against prostate cancer.

Using state-of-the-art, whole-genome sequencing technologies on prostate tumour samples, researchers at the Princess Margaret focused on the often overlooked noncoding regions of the genome: vast stretches of DNA that are free of genes (i.e. that do not code for proteins), but nonetheless harbour important regulatory elements that determine if genes are turned on or off.

Previously dismissed as "junk" DNA, noncoding regions were once thought to have little to offer for a cure against cancer.

But this never dissuaded Dr. Mathieu Lupien, Senior Scientist, Princess Margaret Cancer Centre, to commit his research program to the study of the noncoding genome.

"We are exploring uncharted territory," says Dr. Lupien, who is also an Associate Professor in the Department of Medical Biophysics, University of Toronto, whose lab's tagline is "Decoding cancer through epigenetics."

"Our goal is to conquer cancer in our lifetime. We have to look everywhere including the 'darkest' parts of the genome of cancer cells for that hidden 'gold,'" he says.

In his latest paper, entitled "Cistrome-partitioning reveals convergence of somatic mutations and risk-variants on master transcription regulators in primary prostate tumors," published inCancer Cellon Thursday, Dr. Lupien and a 21-member team of national and international clinicians, scientists, pathologists and computational scientists assessed the role of more than 270,000 mutations found in primary prostate tumours.

They found that these accumulate in specific noncoding regions bound by a specific set of proteins that control the on/off state of genes. Inhibiting these proteins, which Dr. Lupien refers to as "the maestro of the cell," blocks growth of prostate cancer cells, showing their value for drug development.

This represents a new approach that exploits the rich information from all mutations found in tumours, from both coding and noncoding sources. It allows us to prioritize targets for therapy, he explains.

"Just imagine the possibilities the noncoding genome opens up," he adds.

Understanding the non-coding or dark genome is an area of increasing focus for scientists.

In 2003, the Human Genome Project mapped and sequenced the human genome, consisting of all the genes necessary to grow a human being.

It found that about 21,000 protein-coding genes make up about only two per cent of our entire genome the blueprint of life or the human genetic instruction booklet.

And the other 98 per cent of the genome the non-coding (for proteins) portion what role does it play?

Scientists have come to realize that hidden amongst this noncoding DNA are crucial elements that not only control the activity of thousands of genes, but also play a major role in many diseases. Mining this area could provide important sequencing clues for potential cures.

The human genome is incredibly complicated, says Dr. Lupien. He explains that the dark, or as yet undiscovered, portion of the genome contains millions of gene switches, affecting all the cells in our bodies, at various points throughout our lives.

"Now we can start connecting these genetic switches to cancer development to get a more precise understanding of how disease begins and how we can treat it," he says.

Precision medicine currently relies on a few hundred biomarker-drug combination, and we need to expand our list of biomarkers and drugs if we want to deliver on the promise of precision medicine, adds Dr. Lupien. "The inclusion of the noncoding genome in our analysis is a leap in the right direction to achieve our goal," he says.

Reference:Mazrooei, et al. (2019) Cistrome Partitioning Reveals Convergence of Somatic Mutations and Risk Variants on Master Transcription Regulators in Primary Prostate Tumors. Cancer Cell DOI:https://doi.org/10.1016/j.ccell.2019.10.005

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Mining the Genome: Exploring Uncharted Territory To Discover New Drug Targets - Technology Networks

By Stephanie Miceli | Nov. 13, 2019

When Sara Altschule took a 23andMe ancestry test, the results confirmed what she already suspected: She is 77 percent Ashkenazi Jewish. However, months later, after opting into add-on health tests, she received life-changing news: She had a BRCA2 gene mutation, which is particularly prevalent among Ashkenazi Jewish women. Altschules BRCA2 mutation meant her lifetime risk of developing breast cancer is about 69 percent; for ovarian cancer, it is about 17 percent.

As at-home genetic tests grow in popularity, some individuals have expressed concern about the complexities of the results. Speaking about her experience with at-home genetic testing at a recent workshop of the Roundtable on Genomics and Precision Health of the National Academies of Sciences, Engineering, and Medicine, Altschule told attendees, The results not only probably saved my life, but may have also saved the lives of people in my family who now know they are also BRCA2 positive. While empowering for her, she also wishes she had received the results from a genetic counselor not via email.

Traditionally, there have been two main types of genetic testing: traditional tests initiated by a doctor, and direct-to-consumer (at-home) tests. Most people do a combination of both, said keynote speaker Robert Nussbaum, chief medical officer of Invitae. About one-third of people who take an at-home test share the results with a provider, who can make appropriate referrals based on the results, he said.

Knowledge Is Power

After seeing a genetic counselor and getting a more comprehensive blood test, Altschule decided to undergo a preventive double mastectomy at the age of 31. I felt powerless during this process, and I wanted to take my power back. This was the easiest and toughest decision of my life, said Altschule.

Panelist Dorothy Pomerantz, who also received news of her BRCA status via 23andMe, said online test results are not a replacement for a one-to-one conversation with a trusted provider. Pomerantz considers herself lucky to have received actionable information, though she still has complicated feelings about how that information was delivered.

This information is complicated and nuanced. We need someone to walk us through the dark, said Pomerantz. When my genetic counselor confirmed my results, she asked me what I needed in that moment. Did I need to vent? Did I want information? Did I need to be alone or cry?

Affordability Is Part of Accessibility

Aside from having access to genetic testing in the first place, Altschule and Pomerantz acknowledged they had the resources to get immediate follow-up testing and surgery.

What about those who cant get their doctors on the phone? What about those who dont have doctors at all? asked Pomerantz.

Without insurance, someone with a risk of cancer may not have those options, said Sadie Hutson, director of the Cancer Genetics Program at Pikeville Medical Center in Kentucky. In the Appalachian communities where she works, coal mining, the dominant industry, has been linked to high incidences of lung cancer. However, many people have to live with the knowledge of that risk and the inability to act on it.

Affordability of genetic testing is a very real problem, said Hutson.

There is also a dire shortage of genetic counselors in the region, she added. Hutson has partnered with mobile clinics and faith-based organizations that provide genetic testing and counseling free of charge, particularly to the regions Medicaid population. Hutson also noted the importance of offering free follow-up testing to family members.

Panelists discussed the accessibility of direct-to-consumer genetic tests for underserved and rural populations and ways to increase engagement, literacy, and reduce disparities.

Steps Toward Including All of Us

We have a skewed evidence base in human genomics research, said Malia Fullerton, professor of bioethics and humanities at the University of Washington School of Medicine. Because certain populations are underrepresented in research, when they do receive genetic testing, there is a lack of data that they can act on. Joyce Tung, 23andMes vice president of research, acknowledged most of the companys customers are white people of European descent and it wants to change that.

We cant provide information that we dont have, she said. A lack of data can halt progress and new discoveries in diseases that primarily affect diverse communities such as sickle cell disease, which is prevalent in people of African descent. Tung highlighted several initiatives at 23andMe that aim to improve diversity, including the African American Sequencing Project, Global Genetics Project, and the Latino Sequencing Project.

In addition, underrepresented populations are more likely to receive uncertain test results, often because their genetic variants have not been well-studied. As a result, they may experience unnecessary testing or lifestyle changes, or false reassurance, and the psychological burden that comes with it, Fullerton said.

To address the lack of diversity in genetic databases, last year, the National Institutes of Health launched its All of Us research initiative. It aims to collect data from 1 million Americans from various population groups.

The vast majority of 23andMe consumers 80 percent agree to share their data in the hopes of contributing to science and new insights about health and disease. However, the current lack of diversity in genetic databases risks hindering the science.

There is a critical opportunity for multiple sectors to come together to ensure proper inclusion of all individuals in genetic and genomic testing, said Hutson.

Integrating Consumer Genomics into Health Care

Speakers throughout the day acknowledged the challenges around integrating consumer genomics data into clinical care. Consumers often want information fast, but health systems may not be able to quickly provide the confirmation genetic testing following a positive DTC result.

This continuum of care has a lot of access points and a lot of people trying to find pathways, but really it is reflective of the overall health system, said Siobhan Dolan, a professor and vice chair for research at Albert Einstein College of Medicine. Maybe genetics has given people an opportunity to find alternative routes and maybe we could continue to learn from that try to put something together that is continuous.

Visit http://nationalacademies.org/hmd/Activities/Research/GenomicBasedResearch/2019-OCT-29.aspx to view speaker presentations and other information about the Workshop on Exploring the Current Landscape of Consumer Genomics.

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At-Home DNA Tests Still Need the 'Human Touch,' Say Panelists at Genomics Roundtable Workshop - National Academies of Sciences, Engineering, and...

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Researcher Tom Cappola tells us about the latest clinical trials and medical breakthroughs to be announced during Scientific Sessions.

Chief of the cardiovascular medicine division in the Perelman School of Medicine at the University of Pennsylvania, Tom Cappola.

For the first time in its near 100-year history, the American Heart Association (AHA)will host its annual meeting in Philadelphia. AHAs Scientific Sessions is the largest cardiovascular meeting in the United States. On November 16-18, the meeting will attract nearly 18,000 attendees from more than 100 countries to the Pennsylvania Convention Center, and an additional two million medical professionals who will participate virtually in lectures and discussions about basic, translational, clinical and population science innovations aimed at reducing disability and deaths caused by cardiovascular disease and stroke.

The American Heart Association is excited to be in Philadelphia, said Michelle Kirkwood, director of National Science Media Relations for AHA. It has been on our wish list for some time, especially since the renovations at the Pennsylvania Convention Center and the citys landmark, robust nonsmoking laws that align directly with the American Heart Associations health and wellness goals. We are excited for our thousands of attendees to visit Philadelphia.

More than 610,000 people die of heart disease in the United States every year, according to the CDC. While heart disease is a leading cause of death for both men and women, it claims the lives of over 400,000 American women each year, or one death every 80 seconds. During the three-day meeting, more than 12,000 leading physicians, scientists, cardiologists and healthcare professionals in the global cardiovascular health community will host 850 educational sessions and more than 4,100 original research presentations to unveil the late-breaking science, clinical trials, and novel therapeutics and pathways that are shaping the future of cardiovascular care.

Its very fitting for Scientific Sessions to be here, chief of the cardiovascular medicine division in the Perelman School of Medicine at the University of Pennsylvania Tom Cappola said. We have the first medical school in the country and the first teaching hospital in the country. It makes sense that these new innovations would be presented in a place where theres already been so much innovation.

Cappola will be one of several Penn researchers leading the Cardiovascular Expert Theater, Innovations in Cardiovascular Therapies session during the meeting. Here are just a few big trends in heart care that Cappola says we can expect to learn more about during this weekends meeting:

Using artificial intelligence to monitor heart health

Artificial intelligence (AI) is having a big impact on cardiovascular care. Results from two preliminary studies to be presented this weekend will show AI can be used to accurately examine electrocardiogram (ECG) test results to possibly predict irregular heartbeat and risk of death. There will also be a presentation on the Apple Heart Study, which found that the Apple Watch and other wearable remote monitoring devices may be capable of detecting atrial fibrillation (aFib), an irregular and often rapid heartbeat that can lead to blood clots, stroke, heart failure and other complications.

Identifying new risk factors for aFib and stroke

George Mason University researchers will present results from two studies that found young people who smoke marijuana regularly have an increased risk of stroke. According to the study findings, young adults between the ages 18 and 44 who reported frequent use of marijuana, cigarettes and e-cigarettes were three times more likely to suffer stroke than young adults who did not smoke marijuana at all. The study also found that African-American males between the ages of 15 and 24 faced the highest risk of being hospitalized for arrhythmia.

In one Penn study to be presented this weekend, researchers found women who are diagnosed with peripartum cardiomyopathy (PPCM) during late pregnancy or within a month following delivery are more likely to experience restored cardiac function and improved outcomes compared to those who are diagnosed later in the postpartum period. The findings underscore the need for increased awareness and monitoring of heart failure symptoms, particularly among black women, who, on average, are diagnosed significantly later than white patients, according to study results.

Making advances in genetics and genomics

Another big trend at this years meeting will be the continued advancement in genetics and genomics, and how thats impacting cardiovascular care.

I think that genomic medicine has arrived and its arriving in waves, but it will ultimately affect all aspects of cardiovascular care, Cappola said. We have lots of people getting their 23andMe for sort of recreational purposes and they dont know what to do with it. But were starting to figure out what to do with that genetic information to improve care.

Another Penn Medicine study to be presented during the meeting will show why taller people may have an increased risk of developing atrial aFib. The research found a strong link between the genetic variants associated with height and ones risk for AFib, for the first time demonstrating that height may be a causal not correlated risk factor for the condition. Researchers hope insight from human genetics in large studies like this one will help them better understand causal risk factors for common disease.

It takes expertise to find links like this. Thats why researchers go to the American Heart Association meetings. You get all the experts together, they share their knowledge and this helps us to actually figure out what to do with this genetic information, Cappola said. Thats true across the board, but its particularly important for genomic medicine as it continues to advance.

Excerpt from:
The American Heart Association's Annual Conference Comes to Philly This Weekend - Philadelphia magazine

A new study led by researchers at Baylor College of Medicine revealed how in utero Zika virus infection can lead to microcephaly in newborns. The team discovered that the Zika virus protein NS4A disrupts brain growth by hijacking a pathway that regulates the generation of new neurons. The findings point at the possibility of developing therapeutic strategies to prevent microcephaly linked to Zika virus infection. The study appeared Thursday in the journal Developmental Cell.

Patients with rare genetic mutations shed light on how Zika virus causes microcephaly

The current study was initiated when a patient presented with a small brain size at birth and severe abnormalities in brain structures at the Baylor Hopkins Center for Mendelian Genomics (CMG), a center directed by Dr. Jim Lupski, professor of pediatrics, molecular and human genetics at Baylor College of Medicine and attending physician at Texas Childrens Hospital, said Dr. Hugo J. Bellen, professor at Baylor, investigator at the Howard Hughes Medical Institute and Jan and Dan Duncan Neurological Research Institute at Texas Childrens Hospital.

This patient and others in a cohort at CMG had not been infected by Zika virus in utero. They had a genetic defect that caused microcephaly. CMG scientists determined that the ANKLE2 gene was associated with the condition. Interestingly, a few years back the Bellen lab had discovered in the fruit fly model that ANKLE2 gene was associated with neurodevelopmental disorders. Knowing that Zika virus infection in utero can cause microcephaly in newborns, the team explored the possibility that Zika virus was mediating its effects in the brain via ANKLE2.

In a subsequent fruit fly study, the researchers demonstrated that overexpression of Zika protein NS4A causes microcephaly in the flies by inhibiting the function of ANKLE2, a cell cycle regulator that acts by suppressing the activity of VRK1 protein.

Since very little is known about the role of ANKLE2 or VRK1 in brain development, Bellen and his colleagues applied a multidisciplinary approach to tease apart the exact mechanism underlying ANKLE2-associated microcephaly.

The fruit fly helps clarify the mystery

The team found that fruit fly larvae with mutations in ANKLE2 gene had small brains with dramatically fewer neuroblasts brain cell precursors and could not survive into adulthood. Experimental expression of the normal human version of ANKLE2 gene in mutant larvae restored all the defects, establishing the loss of Ankle2 function as the underlying cause.

To understand why ANKLE2 mutants have fewer neuroblasts and significantly smaller brains, we probed deeper into asymmetric cell divisions, a fundamental process that produces and maintains neuroblasts, also called neural stem cells, in the developing brains of flies and humans, said first author Dr. Nichole Link, postdoctoral associate in the Bellen lab.

Asymmetric cell division is an exquisitely regulated process by which neuroblasts produce two different cell types. One is a copy of the neuroblast and the other is a cell programmed to become a different type of cell, such as a neuron or glia.

Proper asymmetric distribution and division of these cells is crucial to normal brain development, as they need to generate a correct number of neurons, produce diverse neuronal lineages and replenish the pool of neuroblasts for further rounds of division.

When flies had reduced levels of Ankle2, key proteins, such as Par complex proteins and Miranda, were misplaced in the neuroblasts of Ankle2 larvae. Moreover, live imaging analysis of these neuroblasts showed many obvious signs of defective or incomplete cell divisions. These observations indicated that Ankle2 is a critical regulator of asymmetric cell divisions, said Link.

Further analyses revealed more details about how Ankle2 regulates asymmetric neuroblast division. They found that Ankle2 protein interacts with VRK1 kinases, and that Ankle2 mutants alter this interaction in ways that disrupt asymmetric cell division.

The Zika connection

Linking our findings to Zika virus-associated microcephaly, we found that expressing Zika virus protein NS4A in flies caused microcephaly by hijacking the Ankle2/VRK1 regulation of asymmetric neuroblast divisions. This offers an explanation to why the severe microcephaly observed in patients with defects in the ANKLE2 and VRK1 genes is strikingly similar to that of infants with in utero Zika virus infection, Link said.

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For decades, researchers have been unsuccessful in finding experimental evidence between defects in asymmetric cell divisions and microcephaly in vertebrate models. The current work makes a giant leap in that direction and provides strong evidence that links a single evolutionarily conserved Ankle2/VRK1 pathway as a regulator of asymmetric division of neuroblasts and microcephaly, Bellen said.

Moreover, it shows that irrespective of the nature of the initial triggering event, whether it is a Zika virus infection or congenital mutations, the microcephaly converges on the disruption of Ankle2 and VRK1, making them promising drug targets.

Another important takeaway from this work is that studying a rare disorder (which refers to those resulting from rare disease-causing variations in ANKLE2 or VRK1 genes) originally observed in a single patient can lead to valuable mechanistic insights and open up exciting therapeutic possibilities to solve common human genetic disorders and viral infections.

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How in utero Zika virus infection can lead to microcephaly in newborns: Baylor research - Outbreak News Today

Scholars are divided on how to regulate heritable genome editing.

Heritable genome editing refers to changing human reproductive cells so that the resulting fetus has genetic changes that its future offspring may inherit.

Proponents of heritable gene-editing champion the possibility of editing out incurable heritable diseases, but others caution that gene editing may have unintended effects. For example, an edit to prevent a child from inheriting a disease might also reduce that childs immunity to other diseases, a concern that is amplified by the fact that any changes to immunity would be heritable.

The debate is no longer theoretical. Shortly after reports of the first live births of gene-edited babies surfaced in 2018, a number of prominent scientists called for a ban on any further experimentation that would result in live births, at least until regulatory schemes were put in place.

This weeks Saturday Seminar explores scholarly works on current and proposed regulatory approaches to heritable gene-editing, as well as the unique challenges to effective regulation given factors like the medical tourism industry.

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The Next Generation's Genes - The Regulatory Review

The taller you are, the higher your risk of developing developing atrial fibrillation, a new study by Penn Medicine says.

The study found a strong association between the genetic variants of height and an increased risk of atrial fibrillation (AFib) a heart condition that causes an irregular and rapid heartbeat. The link appears to be causal, meaning it's more than a correlation.

The studywill be presented on Saturday at the American Heart Association's 2019 Scientific Sessions in Philadelphia.

Researchers analyzed the association by examining data from Genetic Investigation of Anthropometric Trials, a consortium that studied genetic height variants, and Atrial Fibrillation Genetics, a consortium that studied associations between genetic variants and AFib.

They found that the risk of developing AFib increased by 3% for every one-inch increase in height when compared to those who are considered average in height 5 feet, 7 inches.

This association remained strong even after the data was adjusted for additional risk factors, including heart disease and diabetes.

Researchers thenanalyzed more than 7,000 patients enrolled in the Penn Medicine Biobank to study the association on an individual level. They again found again that height and its genetic variants are strongly linked to an increased risk of developing AFib.

Atrial fibrillationcan lead to severe complications such as stroke, blood clots, and heart failure, according to the Mayo Clinic. Patients with AFib do not always exhibit symptoms, but when symptoms do occur they can includepalpitations, shortness of breath and fatigue.

AFib affects more than 33 million people across the world.

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Tall people have a higher likelihood of developing atrial fibrillation, Penn researchers say - PhillyVoice.com