StemCell Therapy

Scientists piece together the inflammation mechanism in IgG4-related disease, an autoimmune condition with no current cure, revealing possible therapeutic targets

IgG4-related disease is an autoimmune disorder affecting millions and has no established cure. Previous research indicates that T cells, a major component of the immune system, and the immunoglobulin IgG4 itself are key causative factors, but the mechanism of action of these components is unclear. Now, Scientists from Tokyo University of Science have meticulously explored this pathway in their experiments, and their research brings to light new targets for therapy.

Autoimmune diseases are a medical conundrum. In people with these conditions, the immune system of the body, the designated defense system, starts attacking the cells or organs of its own body, mistaking the self-cells for invading disease-causing cells. Often, the cause for this spontaneous dysfunction is not clear, and hence, treatment of these diseases presents a major and ongoing challenge.

One recently discovered autoimmune disease is the IgG4-related disease (or IgG4-RD), which involves the infiltration of plasma cells that are specific to the immunoglobulin (antibody) IgG4 into the body tissue, resulting in irreversible tissue damage in multiple organs. In most patients with IgG4-RD, the blood levels of IgG4 also tend to be higher than those in healthy individuals. Previous studies show that T cellswhich are white blood cells charged with duties of the immune responseplay a key role in the disease mechanism. In particular, special T cells called cytotoxic T lymphocytes, or CTLs, were found in abundance from the inflamed or affected pancreas of patients, along with IgG4. But what was the exact role of CTLs?

In a new study published in International Immunology, a team of scientists from Tokyo University of Science decided to find the answer to this question. Prof. Masato Kubo, a member of this team, states that their aim was twofold. We planned to explore how IgG4 Abs contributes to the CTL-mediated pancreas tissue damage in IgG4-RD, and also to evaluate the pathogenic function of human IgG4 Abs using the mouse model that we have established. The latter is especially important, as IgG4 is not naturally present in mice, meaning that there is a severe lack of adequate animal models to explore this disease.

With these aims, they selected mice that have been genetically programmed to express a protein called ovalbumin (the major protein in egg white) in their pancreas. Then, they injected IgG4 that specifically targets ovalbumin into the mice. Their assumption was that IgG4 would target the pancreas and bring about IgG-4-RD-like symptoms. However, what they found was surprising. No inflammation or any other symptom typical of IgG4-RD appeared. This convinced the researchers that IgG4 alone was not the causative factor of IgG4-RD.

Next, to check if it was the CTLs that were perhaps the villain of the story, the scientists injected both IgG4 specific against ovalbumin as well as CTLs. Now, the pancreas of the mice showed tissue damage and inflammation. Thus, it was established that the presence of CTLs and IgG4 was necessary for pancreatic inflammation.

When they probed further, they found that another variation of T cells, known as T follicular helper or TFH cells, which develop from the natural T cells of the mice, produce self-reactive antibodies like IgG4, which induce inflammation in combination with CTLs.

Once the puzzle was pieced together, the scientists now had the opportunity to zero in on the target step for intervention; after all, if one of these steps is disrupted, the inflammation can be prevented. After much deliberation, they propose that Janus kinase, or JAK, can be a suitable target. JAK is a key component of the JAK-STAT cellular signaling pathway, and this pathway is an integral step in the conversion of natural T cells of the mice to TFH cells. If this JAK is inhibited, this conversion will not take place, meaning that even the presence of CTLs will not be able to induce inflammation.

Prof. Kubo also suggests a broader outlook, not limited to the therapeutic option explored in the study. He states, based on our findings, the therapeutic targets for IgG4-related diseases can be the reduction of TFH cell responses and the auto-antigen specific CTL responses. These can also provide the fundamental basis for developing new therapeutic applications.

These proposed therapeutic targets need further exploration, but once developed, they have the potential to improve the lives of millions of patients with IgG4-RD worldwide.

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Reference

Journal:

International Immunology

About The Tokyo University of Science

Tokyo University of Science (TUS) is a well-known and respected university, and the largest science-specialized private research university in Japan, with four campuses in central Tokyo and its suburbs and in Hokkaido. Established in 1881, the university has continually contributed to Japans development in science through inculcating the love for science in researchers, technicians, and educators.

With a mission of Creating science and technology for the harmonious development of nature, human beings, and society, TUS has undertaken a wide range of research from basic to applied science. TUS has embraced a multidisciplinary approach to research and undertaken intensive study in some of todays most vital fields. TUS is a meritocracy where the best in science is recognized and nurtured. It is the only private university in Japan that has produced a Nobel Prize winner and the only private university in Asia to produce Nobel Prize winners within the natural sciences field.Website: https://www.tus.ac.jp/en/mediarelations/

About Professor Masato Kubo from Tokyo University of Science

Dr Masato Kubo is a Professor at the Tokyo University of Science. A respected and senior researcher in his field, he has more than 226 publications to his credit. He is also the corresponding author of this study. His research interests include Immunology and Allergology. He is the team leader at the Laboratory for Cytokine Regulation, RIKEN Center for Integrative Medical Sciences.

Funding information

This study was supported by grants from JSPS KAKENHI (grant no. 19H03491), Japan Agency for Medical Research and Development (AMED), AMED-CREST, and Toppan Printing CO., LTD.

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Solving the puzzle of IgG4-related disease, the elusive autoimmune disorder - QS WOW News

CLEVELAND, Ohio Immunotherapy, which boosts a patients immune system to destroy cancer cells, is widely seen as the future of cancer care.

This kind of therapy uses substances made by the body, or in a laboratory, to improve or restore the immune system. It can slow the growth of cancer cells, help the immune system do a better job of destroying tumors and slow the spread of cancer to other parts of the body.

There are several kinds of immunotherapy, including CAR-T cell therapy and immune checkpoint inhibitors. In CAR-T, white blood cells called T cells are genetically modified to activate the immune system to recognize and destroy certain cancers.

Immune checkpoint inhibitors are drugs that block proteins made by some immune system cells. When these proteins are blocked, T cells are better able to kill cancer cells.

Cancer vaccines, which are used to prevent and treat cancer, also are a kind of immunotherapy.

Have you or a family member experienced immunotherapy treatment for cancer? Was the treatment effective or ineffective? We want to hear your story.

Please write a short email, no more than 500 words, about your experiences with immunotherapy. Include your full name, age, city and daytime phone number. Your name, age and city will be published with your comment, but your phone number will be kept private.

Comments must be received by Friday, Jan. 10.

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When it came to biomedical breakthroughs, this past decade represented a lot more hype than substance. We were promised a new era of "precision medicine," where every patient would receive highly personalized treatments to target specifics fault in their genes. But in recent months, reports surfaced that these experimental therapies were failing most of the time.

Vas Bailey, a biotech investor with Artis Ventures, acknowledges that it might have seemed like a disappointing decade, barring a few important breakthroughs in the fields of gene editing and therapeutics. But Bailey thinks that there's a lot more to the story.

In recent years, he notes, scientists have focused on the "tools and building blocks" that will drive the breakthroughs in next decade.

"With HIV, we made progresses in life expectancy but didn't cure it; with gene-editing, we achieved one approval that could lay the foundation for others; with AI we learned how to develop it, but haven't yet applied it; and with the microbiome, we have learned more about the relationships (between organisms) but we still haven't designed next generation drugs."

So with the help of a team of biotech experts, here's our list of the most important advancements in biomedicine, many of are likely to propel great advancements going forward.

CAR-T sounds like the stuff of science fiction: Take blood from a cancer patient, re-engineer the blood cells to target and fight cancer cells, and re-infuse the cells in the human body.

But it's real, with the U.S. Food and Drug Administration granting approval in 2017 to the first two drugs that use this approach: Novartis's Kymriah for acute lymphoblastic leukemia (ALL) and Gilead Sciences' Yescarta for certain types of non-Hodgkins lymphoma.

But this therapeutic approach has faced roadblocks, including price -- the drugs cost hundreds of thousands of dollars -- and the logistical complexity of making a treatment out of the patient's own T cells. It can take up to a month to manufacture the cells while the patient's health might be getting progressively worse from the cancer. But this decade also saw progress in companies making off-the-shelf T cells, which are made from healthy donor cells and used for multiple patients.

The next ten years could see advances in using these donor cells -- in particular, reducing the likelihood that patients' immune systems will attack them -- by applying technologies and tools like CRISPR/Cas9.

And that brings us to...

Jennifer Doudna, inventor of the revolutionary gene-editing tool CRISPR photographed in the Li Ka Shing Center on the Campus of the University of California, Berkeley.

Nick Otto | The Washington Post | Getty Images

CRISPR has been hailed as one of the most important breakthroughs of all time. It's essentially a pair of molecular scissors, or a technique to make precise edits in DNA. It was discovered by scientists while exploring the immune system of bacteria.

Scientists have subsequently learned that there are risks to making these modifications. There are also ethical considerations, which were brought to the fore this decade when a scientist in China called He Jiankui reported that he had used the technology to create the first human babies with CRISPR-edited genes.

But this decade ended on a positive note. NPR reported that the first patient in the United States with a genetic disease -- a blood disorder called sickle cell anemia -- was treated with the CRISPR technique. The director of the National Institutes of Health Dr. Francis Collins, told NPR it could give patients a "chance for a new life."

After decades of research into better treatments for Hepatitis C, a debilitating liver disease that could affect as many as 4 million Americans, the U.S. Food and Drug Administration approved a new treatment in 2017 that can reverse the disease in as little as 8 weeks.

The drug from AbbVie followed approvals for similar drugs from fellow drug makers Gilead and Merck, providing a welcome alternative to the prior regimen of shots and pills that didn't always work and came with many side effects. Gilead, which saw its first drug for Hepatitis C approved in 2013, provided a cure in 12 weeks for about 90 percent of patients.

The drugs are extremely expensive, and led to a big spike in revenues for Gilead, but new entrants will provide more competition, potentially leading to lower prices.

A man checks in with a program manager after driving nearly three hours to get to his appointment at Open Arms Healthcare Center on Wednesday, January 23, 2019, in Jackson, MS. Open Arms provides PrEP, or Pre-exposure prophylaxis, which is "a way for people who do not have HIV but who are at substantial risk of getting it to prevent HIV infection by taking a pill every day," according to the CDC.

Jahi Chikwendiu | The Washington Post | Getty Images

This decade, scientists did not cure HIV, the virus that causes AIDS, but they did make some major breakthroughs.

In 2012, the Food and Drug Administration approved Truvada, the first drug to reduce the risk of HIV infection in uninfected individuals who might be at high risk. The drug, which can be taken daily, is used for pre-exposure prophylaxis (PrEP) to lower chances of becoming infected with HIV if exposed.

Unlike some of the other breakthroughs on this list, Truvada has become more pervasive and widespread throughout the decade as costs have come down. The Trump Administration recently unveiled a plan to make these drugs free for people who don't have insurance coverage, and virtual medicine companies like Nurx and Plushcare have sprung up to prescribe PrEP online without a lab visit.

A young boy is handed a certificate confirming he is Ebola-free, outside the Ebola treatment centre in Beni, eastern Democratic Republic of the Congo.

Sally Hayden | SOPA Images | LightRocket | Getty Images

In November of 2019, European regulators finally approved an immunization against Ebola. That decision means that Merck can market its vaccine and distribute it beyond Africa. It has also been approved by regulators in the U.S.

Several vaccines are in development to prevent the outbreak of the fever, which causes such symptoms as diarrhea and bleeding, but Merck's is the only one that was tested during a real outbreak from 2014 to 2016. Ebola has killed more than 2,000 people in the Congo since the middle of this year alone.

Merck has said that it expects to start manufacturing licensed doses of the vaccine in the third quarter of 2020, and that it is working closely with the U.S. government, public health organizations and other groups.

These are just five of the breakthroughs from the past decade, which also saw developments in new "biologic" drugs, which contain or are produced from living organisms, advancements in prosthetics, and in a heartwarming twist, a new medicine for a single patient.

But as Bailey reminds, the best might still be to come. In the past ten years, scientists also made great strides to map out all the cells in the human bodyand to understand contributors to disease encoded in DNA. Teams of researchers also sought to create reference databases for the collections of microbes living in our bodies, and computer scientists teamed up with biologists to extract meaning from huge volumes of medical information, including X-ray imaging and pathology slides.

With all this in mind, Bailey thinks we could see in the next ten years regulatory approvals for the first blood test to screen for cancer at the earliest stages, new therapies that take advantage of our understanding of RNA (the intermediary between DNA and the proteins it instructs the body to make), drugs based on our ever-growing knowledge of the human microbiome, a cure for HIV, and novel approaches to ending multi-drug resistance.

What we've built in recent years are "enabling systems," said Bailey, "and we will benefit from it in the next decade."

Follow @CNBCtech on Twitter for the latest tech industry news.

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These biomedical breakthroughs of the decade saved lives and reduced suffering - CNBC

Science News drew more than 15 million visitors to our website this year. Heres a rundown of the most-read news stories of 2019 that didnt make our Top 10 list, as well as the most popular longer reads.

1. A chip made with carbon nanotubes, not silicon, marks a computing milestoneResearchers built a new kind of computer chip with thousands of carbon nanotube transistors. Though the prototype cant yet compete with silicon chips, carbon nanotube computing technology could lead to faster electronics (SN: 9/28/19, p. 7).

2. People can sense Earths magnetic field, brain waves suggestPeoples brain waves showed a distinct pattern when exposed to an Earth-strength magnetic field pointing in a specific direction in the lab. That finding hints that humans may have magnetoreception, similar to birds and certain other organisms .

Headlines and summaries of the latest Science News articles, delivered to your inbox

3. In a first, scientists took the temperature of a sonic black holeThe temperature of a lab-made black hole that traps sound instead of light agrees with a prediction by cosmologist Stephen Hawking: that black holes emit a small stream of particles called Hawking radiation (SN: 6/22/19, p. 14).

4. Why kids may be at risk from vinyl floors and fire-resistant couchesChildren from homes with all vinyl flooring and flame-retardant couches had higher levels of some potentially harmful chemicals in blood and urine than other kids did, one study found. The finding suggests that these home furnishings release the chemicals quickly enough for them to build up in residents bodies (SN: 3/16/19, p. 14).

5. Archaeologists tie ancient bones to a revolt chronicled on the Rosetta StoneAn ancient soldiers skeleton unearthed from Egypts Nile Delta may be physical proof of a revolt around 2,200 years ago. The Rosetta Stone describes the victory of pharaoh Ptolemy V, from a Greek dynasty, over a faction of the native Egyptian revolt. But archaeological evidence of the uprising is scarce.

1. Vitamin D supplements arent living up to their hype Vitamin Ds popularity soared after findings hinted that it could protect against multiple sclerosis, asthma, depression, heart disease, cancer and other ailments. But a series of studies has cast doubt on these supposed benefits (SN: 2/2/19, p. 16).

2. Measles erases the immune systems memoryMeasles wipes away the immune systems memories of germs it has previously fought. This immune amnesia can leave people at risk of infections from harmful viruses and bacteria for months to years (SN: 6/8/19, p. 20).

3. With its burning grip, shingles can do lasting damageThe virus responsible for chicken pox can lay dormant for decades, only to reemerge later in life as shingles. The disease is more than just a painful rash. Shingles can damage arteries and may raise the risk of stroke and dementia, scientists are finding (SN: 3/2/19, p. 22).

4. The CBD boom is way ahead of the scienceFood, health and wellness products infused with cannabidiol, also known as CBD, are becoming increasingly popular. The substance, derived from cannabis plants, is sold as a remedy for pain, anxiety, insomnia and other conditions without getting the user high. But most health benefits attributed to CBD dont yet have scientific backing (SN: 3/30/19, p. 14).

5. How the periodic table went from a sketch to an enduring masterpieceScience News kicked off its coverage of the periodic tables 150th anniversary with a look at Russian chemist Dmitrii Mendeleev, whose original table had just 63 elements. Scientists have since added many more elements to the table, one of the most important tools in chemistry (SN: 1/19/19, p. 14).

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These are the most-read Science News stories of 2019 - Science News

The immune system coordinates a complex array of components consisting of specialised organs, cells and proteins. On the surface, the primary role of the immune system in defending the body against infectious pathogens might appear straightforward. This begs the question: why is the immune system so complicated?

There are a number of reasons for this degree of complexity. The first is that the immune system evolved to fight pathogenic infection while minimising collateral damage to healthy tissue. For sake of argument, if the lungs of a patient were infected with a pathogenic microorganism, the immune system could release molecules that would kill the pathogen. However, if these molecules were to be released in an uncontrolled and directionless fashion, healthy tissue would be destroyed too.

This analogy raises another important feature of the immune system, namely, the recognition of differences between healthy cells and pathogens referred to as self and non-self respectively.

Each one of us has a personal army of immune cells that are programmed to harmoniously communicate with one another ensuring discrimination of self from non-self and efficiently respond to infection. Inflammation is a key process that ensures the recruitment of immune cells and proteins to the site of infection.

Among these are killer immune cells and antibodies that specifically neutralise pathogen-associated molecules called antigens. Once the pathogen is eliminated, other immune cells play a key role in restoring normal conditions by promoting tissue repair processes.

In autoimmune disorders, rogue immune cells fail to recognise healthy tissue as self and attack it. Among such disorders are psoriasis, lupus, rheumatoid arthritis, multiple sclerosis, Crohns disease and type I diabetes. Overall, they affect 5 per cent of the population in industrialised countries.

Autoimmune responses resemble normal immune responses but are initiated by self-antigens rather than pathogen-associated antigens. The human body has evolved a multitude of checkpoints that prevent the immune system from attacking healthy tissue. Together, these checkpoints must act concertedly to strike a delicate balance of dampening autoimmune responses while maintaining the ability of the immune system to strike against pathogenic infection. Indeed, it is quite common to observe isolated breakdown of one of these checkpoints in healthy individuals without any clear consequences.

Autoimmunity occurs when there is a collapse of enough checkpoints resulting in sustained reaction to self-antigens ultimatelyleading to tissue damage. In autoimmunity, self-antigens are not eliminated by the immune system. The constant presence of self-antigen leads to a salient feature of autoimmune disorders called chronic (sustained) inflammation, which leads to a continuing self-destructive process. Both auto-antibodies and killer cells directed at self-antigens participate in this immune mediated tissue damage.

The focus of my research is, therefore, directed at understanding how immune cells recognise antigens and communicate effectively with one another. Understanding these events is relevant in developing future therapies where the immune system plays a central role and intervention can help balance its response to disease.

David Saliba is a senior lecturer in the Department of Applied Biomedical Sciences, Faculty of Health Sciences at the University of Malta and also holds an honorary research fellow position at the Kennedy Institute of Rheumatology at the University of Oxford.

Identifying the cause of auto-immune disorders. While we understand the complex mechanisms that result in autoimmunity, intense research by the scientific community is directed at identifying the root cause of each of these disorders. In recent years, it has become clear that both genetic and environmental factors contribute to the development of autoimmune disorders. Genetic studies have identified multiple genes that contribute to increased susceptibility to autoimmune diseases. On the other hand, it is much more difficult to identify environmental influences. This is partly due to the chronic nature of these disorders. It is hard to pinpoint exactly when the autoimmune response began and therefore challenging to determine the single or combination of environmental triggers.

Imbalance in gut flora linked to Rheumatoid arthritis. The intestinal gut flora is an intricate world of microbes that has important implications in proper development of the immune system. Alterations of non-pathogenic microbial populations are often associated with immune disorders, particularly of the autoimmune kind. Rheumatoid arthritis is a debilitating disease since it primarily affects the hands, wrists and synovial joints. Scientists have compared faecal microbes of healthy individuals to rheumatoid arth-ritis patients. These studies have evidenced a clear shift in microbial populations demonstrating that specific microbial species may be responsible for the onset and progression of rheumatoid arthritis. It will be exciting to see how this field shapes the development of novel therapeutic approaches and biological markers of this disease.

For more soundbites listen to Radio Mocha every Saturday at 7.30pm on Radju Malta and the following Monday at 9pm on Radju Malta 2 https://www.fb.com/RadioMochaMalta/

To test the first barcode design, IBM employees hired a softball pitcher to fling one attached to a bean bag as fast as he could past a scanner.

Word of the Day: Cryptophasia when twins develop a language that only they can understand.

The board game The Campaign for North Africa is famously complex. It has 1,800 pieces, three volumes of rules and takes teams of five 1,500 hours to complete.

Jingle Bells was originally a Thanksgiving song.

Online porn has the same carbon footprint as the whole of Belgium.

Drinking alcohol with a diet mixer gets you 18 per cent more drunk than regular mixer.

For more trivia see: http://www.um.edu.mt/think

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Autoimmune disorders when the body attacks itself - Times of Malta

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Napping may boost your heart health. That's the finding of researchers in Switzerland, who tracked 3,462 healthy adults for five years. Those who dozed for five minutes to an hour once or twice a week were 48 percent less likely to suffer a heart attack, stroke, or heart failure than those who never snoozed in the daytime. Napping longer or more often didn't deliver any additional health benefits. Lead author Nadine Husler says it's still unclear how napping might influence heart health. "Our best guess," she says, "is that a daytime nap just releases stress from insufficient sleep."

Eating mushrooms could lower your chances of developing memory problems in later life. A study involving 663 Chinese men and women found that those who ate one or two 5-ounce portions of mushrooms a week had a 43 percent lower risk of developing mild cognitive impairment a precursor to Alzheimer's than participants who consumed less than one. Those who ate more than two portions had a 52 percent reduced risk. Lead author Lei Feng says the most likely explanation for this "dramatic effect" is that the fungi contain antioxidants that protect neurons from damage.

Having kids makes you happier once they've grown up and moved out. Previous research has shown that, earlier in life, people with children are less happy and more prone to depression than childless peers, partly because they get less sleep and experience more stress. But a study of 55,000 Europeans found that parents were more likely to be happier when they got older, provided their offspring had flown the nest. Researchers say grown kids can offer parents more social and emotional connection, as well as care and other support. "There is no simple answer on whether children bring happiness," says lead author Christoph Becker. "It depends on which stage of life your children are at."

Running just once a week could significantly cut your risk of a premature death. Researchers in Australia looked at 14 studies that tracked the health of some 230,000 people for up to 35 years. Those who did any running at all were 27 percent less likely to die early. Surprisingly, the runners who ran longer distances or at a faster pace didn't see their risk decline any further just 50 minutes of jogging a week was enough. "If you are physically inactive and don't have much time on your hands for exercise," says lead author Zeljko Pedisic, "running might just be the right activity for you."

NSAIDs such as aspirin and ibuprofen may help relieve depression. In an analysis of previous studies, researchers in China found that a daily dose of nonsteroidal anti-inflammatory drugs (NSAIDs) was 79 percent more effective than a placebo at eliminating depressive symptoms. Several studies have linked depression to brain and body inflammation, leading to speculation that an overactive immune system which can cause inflammation could be a factor. Alan Carson, who edited the study, says depression "may simply be the price we pay for having an immune system."

Northern Irish soil could have healing properties. Residents of the Boho Highlands have been using the alkaline dirt from a local churchyard as a folk remedy for 200 years. An analysis of this "sacred clay" revealed that it contains a previously unknown strain of Streptomyces bacterium that can halt the growth of four of the top six superbugs resistant to conventional antibiotics. Scientists believe such traditional medicines may prove to be a useful source of new antibiotics. "Some of these cures might have been perfectly effective," says co-author Gerry Quinn. The people "just didn't have any knowledge of the scientific principles or biochemistry behind them."

High-fiber foods can shrink your risk of dying early or developing a chronic condition. A scientific review commissioned by the World Health Organization noted that people who ate the most fiber found in fruit, vegetables, and whole-grain cereals, pasta, and bread were 15 to 30 percent less likely to die prematurely than those who ate the least. Heavy fiber consumers were also 16 to 24 percent less likely to suffer a stroke or develop heart disease, type 2 diabetes, or colorectal cancer. The optimal fiber intake was 25 to 29 grams a day; American adults consume an average of 15 grams.

Playing soccer may increase your risk of neurodegenerative disease. Researchers in Scotland compared the deaths of 7,676 male former pro soccer players with those of more than 23,000 people from the general population. The ex-players had a longer life expectancy overall, but a 3.5 times higher risk of dying from diseases such as Alzheimer's and Parkinson's. While soccer players don't endure the same kind of crashing tackles that can cause degenerative brain disease in football players, frequent heading of the ball can alter the makeup of the brain. "It is not just the 'big hits' resulting in symptomatic concussions that increase the risk of neurologic disorders later in life," says neurologist Robert Stern.

Aspirin could significantly raise the chance of dangerous bleeds in the gut and skull. A daily dose of the blood-thinning drug can help prevent heart attacks and strokes for those with existing cardiovascular issues. But a review by British scientists of 13 previous studies found that for people with no issues, the cons outweigh the pros. Overall, aspirin reduced the risk of cardiovascular problems by 11 percent but was linked to a 43 percent increase in significant bleeding events. Co-author Sean Lee Zheng says that before prescribing the drug, physicians should weigh "any small potential cardiovascular benefits [against] the real risk of severe bleeding."

Ultraprocessed foods can shorten your life. A French study found that every 10 percent increase in consumption of these foods such as chicken nuggets, potato chips, and ready-to-eat meals was linked to a 14 percent higher risk of early death. The researchers say some additives in ultraprocessed products are carcinogenic and that chemicals from packaging may leak into the foods. Co-author Mathilde Touvier recommends people "avoid these foods as much as they can."

Getting a tattoo can put toxic metal fragments in your body. German scientists examined 12 new steel tattoo needles with a high-powered microscope, both before and after use. They found that chromium and nickel particles break off during the tattooing process and become embedded in the skin. Those metals can travel through the body and build up in lymph nodes, potentially triggering an allergic reaction. Anyone thinking of getting inked, says lead author Ines Schreiver, should be aware they could be exposed to "impurities that might be allergenic or carcinogenic."

Vaping may damage blood vessels. Using MRI scans, University of Pennsylvania scientists monitored blood flow in 31 nonsmokers. After participants had several puffs on an e-cigarette without a flavor or nicotine, their blood flow was noticeably worse. Overall, vaping temporarily constricted arteries in the legs, heart, and brain by more than 30 percent. The researchers believe glycerol and propylene glycol, the core ingredients of vape fluid besides water, can irritate the lining of blood vessels. More than 2,400 people have been hospitalized over the past year for vaping-related lung illnesses, and at least 52 have died. Scientists suspect many had vaped illicit liquids containing THC the psychoactive compound in marijuana that had been cut with vitamin E acetate, a sticky oil that can cling to the lungs.

Also from The Week: The best things you didn't watch, read, and listen to in 2019

Doctors' coats are often contaminated with dangerous bacteria and other pathogens. A review of previous studies found that up to 16 percent of the garments tested positive for MRSA, and up to 42 percent for Gram-negative rods antibiotic-resistant bacteria that can cause skin and blood infections, sepsis, pneumonia, and other health issues. Researchers found that stethoscopes, phones, and digital tablets can also be contaminated with dangerous bacteria. Previous studies have found that most American physicians wash their coats less than once a week; up to 17 percent go more than a month between washes.

White meat may raise your cholesterol levels as much as red meat. Researchers put 113 adults on three rotating monthlong diets: one centered on lean cuts of beef, the second on lean cuts of chicken, and the third on plant proteins. Half the participants' diets irrespective of their main protein source were high in saturated fats, while half were low. Overall, white meat raised levels of LDL cholesterol, the so-called bad cholesterol that clogs arteries, just as much as red meat even when saturated fat levels were equal.

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The best health advice from 2019 - The Week

Exercise is good for you. Thats hardly news: People who exercise tend to have longer, healthier lives. But until recently, researchers have tallied its benefits only in narrow slices: Exercise lowers your cholesterol and blood pressure; it keeps you from getting fat. Now its becoming clear that those known slices dont add up to the full pie.

When people totaled up those effects, they only account for about half the benefit, says Michael Joyner, an exercise physiologist at the Mayo Clinic in Rochester, Minnesota. So whats contributing to the biomedical dark matter?"

To solve that mystery, researchers are now digging deeper into the mechanisms that underlie the benefits of physical activity. They are finding that exercise is both powerful and wide-reaching, affecting not just muscles and the cardiovascular system, but almost every part of the body, from the immune system to the brain to the energy systems within individual cells. And as scientists understand more precisely which levers exercise pulls to improve our health, clinicians are on the verge of being able to change their practice. The goal is to think of exercise as a medicine a therapy that they can prescribe in specific doses for specific needs.

Its like your own personal regenerative medicine, says Joyner.

Scientists have long known that some of the benefits of exercise are a simple matter of plumbing. Exercise makes blood vessels bigger and keeps them functioning smoothly, which makes them less likely to plug up and cause a heart attack or stroke. There have been hints that this may also mean more blood flow to the brain, which could help prevent cognitive decline. For example, studies have linked exercise to a reduced risk of Alzheimers.

Now researchers are making a more explicit connection between exercise and brain health. They are discovering that the full benefit of exercise comes not from mere physical movement but from actual physical fitness, the bodys cardiovascular health. A long-term study of Norwegian military recruits, for example, found that theiraerobic fitness at age 18 was highly predictive of their risk of dementiain old age. And Swedish women who were highly fit in middle age had aneight times lower risk of dementiaover the next 44 years than women of only moderate fitness, researchers reported in 2018 inNeurology.

Another recent study, led by K. Sreekumaran Nair, an endocrinologist at the Mayo Clinic, found that after just 12 weeks of a high-intensity exercise regimen, participants brains showedincreased glucose uptake and higher metabolic activity, particularly in regions that usually show decline in Alzheimers disease.High-intensity exercise was found to have a similar effecton the parts of the brain most affected by Parkinsons disease, in research led by Marcas Bamman, an exercise physiologist at the University of Alabama at Birmingham.

Exercise doesnt just build bigger blood vessels; it also builds bigger muscles. That benefits health in a number of ways, from minimizing the risk of diabetes to enhancing the bodys immune response to ills such as cancer.

Muscle is the largest consumer of all the glucose that floods into the bloodstream after a meal. More muscle means quicker removal of this glucose surge, says Bamman and therefore, less exposure to the harm caused by elevated blood sugar, a serious health issue for people prone to diabetes.

Just getting the minimum recommended amount of exercise (7.5 metabolic equivalent (MET) hours per week) reduces mortality risk by 20 percent compared with no exercise at all. Exercising a little more than that minimum continues to reduce the risk, but such benefits taper off after about three times the recommended minimum. (MET is the ratio of a person's working metabolic rate relative to their resting metabolic rate, 1 MET is the rate of energy expenditure while at rest, walking at 3 to 4 miles-per-hour is considered to require 4 METs.)

The muscle-building aspects of exercise also help reverse a key change associated with aging: a decline in the function of mitochondria, our cells energy generators. This decline, often seen in sedentary individuals, can leave the mitochondria unable to completely burn the cellular fuel and that can lead cells to generate more oxidants, the oxygen-rich, reactive molecules that damage proteins and DNA.

Muscles are chock-full of mitochondria and exercise can help avoid this oxidative damage. Nairs studies show that aerobic exercise, alone or in combination with strength training,improves peoples mitochondrial function, reduces the production of oxidants and forestalls oxidative damage. High-intensity aerobic exercise alsoencourages mitochondria to produce more of the proteinsthey use to burn fuel.

Muscle has another important role: Its abundant proteins serve as reservoirs of amino acids for the rest of the body. Usually, when other organ systems need amino acids, says Bamman, those are drawn from muscle. Thats especially important when someone is sick because the immune system needs lots of amino acids to make antibodies that fight infection.

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The biggest benefit from building muscle, though, may come from the signaling molecules it pumps into the blood. Bente Klarlund Pedersen, an exercise physiologist at the University of Copenhagen, identified the most-studied of these signaling molecules back in 2000, and later coined a term for them: myokines. Since then, she and other researchers have found hundreds more, many of which are activated by exercise. These molecules, which are released in response to muscular exertion, help regulate muscle growth, nutrient metabolism, inflammation and a host of other processes. I think for most people its difficult to understand why muscle work can influence my liver or be good for my brain or bones, she says. Myokines serve as the link between muscle activity and these other organs.

One of the most important myokines in this crosstalk is interleukin-6. Released in response to muscular exertion, IL-6 has several effects, includingsuppressing hungerandenhancing the immune systems response to cancer. Another signaling molecule, cathepsin B, triggersbeneficial changes in the brain, including the production of new brain cells. Other signaling molecules can help moderate depression.

Exercise, of course, also helps keep you thinner and especially, it forestalls the accumulation of abdominal fat, a particularly harmful sort. One reason abdominal fat is so bad for you is its partnership with inflammation. If we take out visceral fat and study it in the lab, we see that visceral fat is more inflamed than subcutaneous fat, says Pedersen. This inflammation will spill over into the blood, causing chronic systemic inflammation.

Chronic inflammation, Pedersen suggests in the 2019Annual Review of Physiology, may be the underlying reasonwhy inactivity contributes to so many different diseases. We know that being physically inactive increases the risk of approximately 35 different diseases or disorders, she says. And if you have one of these diseases lets say you have type 2 diabetes you have increased risk of others, like cancer or heart disease. If we tie it all together, one feature of all these diseases is physical inactivity, and the other is chronic inflammation.

Even a few weeks of inactivity can cause fat to accumulate in the abdomen, which spurs chronic inflammation throughout the body. This inflammation contributes to a range of ailments, including type 2 diabetes, cardiovascular disease and Alzheimers disease.

About a decade ago, Pedersen conducted an experiment in which she had healthy young men reduce their daily step count from about 10,000 steps per day to just 1,500. Within two weeks, the men showed a7 percent increase in abdominal fat mass. Along with this change, the men showed hints of reduced insulin sensitivity, a change also seen in type 2 diabetes.

Interleukin-6 appears to be at the heart of exercises effect on visceral fat and inflammation. In a recent experiment, Pedersen and her colleagues put 27 potbellied volunteers on a 12-week exercise-bike program, while 26 other volunteers remained inactive. Half the participants in each group also received a drug that blocks the action of IL-6. At the end of the 12 weeks, the exercisers had lost abdominal fat, as expected butonly if they had not received the IL-6 blocker. (Oddly, IL-6 is generally thought of as a pro-inflammatory molecule, because it is more abundant in obese people with systemic inflammation. But Pedersen has some evidence that in these people, elevated IL-6 is an effect, not a cause, of the inflammation.)

As researchers tease out more of the details about how physical activity benefits health, the moment is fast approaching when exercise becomes not merely a good thing to do, but a medicine in its own right, just like pharmaceutical drugs. Several studies already point in this direction. For example, more than half of 64 adults with type 2 diabetes were able tostop taking medication to lower their blood sugarwithin a year of beginning a regular exercise program, Pedersen and her team found. And a survey of more than 300 randomized controlled trials found thatexercise was just as effective as drugsfor people at risk of heart disease and diabetes, and was more effective than drugs for rehab after a stroke.

But if exercise is to truly become a medicine like any other, clinicians will need to learn how much to prescribe to maximize its benefits. Just saying be physically active is like telling people eat better it doesnt tell us what we should be doing, says Kirk Erickson, an exercise psychologist at the University of Pittsburgh. But developing more precise dosing recommendations is difficult, because there are so many ways to exercise, which vary in duration, intensity, frequency and kind. (Tailoring to individual disease risks telling one person to doX because theyre at risk of diabetes, and another person to doY because of a family history of dementia is an even more distant goal.)

Researchers are still working out what matters in this complex arena. Exercises that involve more muscle groups generate more IL-6, so full-body exercises like running have a greater anti-inflammatory effect than exercises that target just a few muscle groups, says Pedersen. And the benefits go away within a couple of days, suggesting that exercising frequently is important. If its been 48 hours since you exercised, its time to do it again, says Jill Barnes, an exercise physiologist at the University of WisconsinMadison.

A series of upcoming randomized trials may soon bring more certainty to the dosing question. One of the largest, which Bamman is involved with at the University of Alabama, will have nearly 2,000 volunteers undertaking either 12 weeks of endurance exercise, 12 weeks of weight training or no exercise program. Researchers will measure gene activity, molecular signaling and other changes within the body, which could allow them topin down exactly how these two modes of exercise differin effect. Because the study is so large, researchers should also be able to explore why some people respond more strongly than others to the same dose of exercise.

Another large study that Bamman is participating in, funded by the US Department of Defense, aims to comparegenes activated by moderate exercise to those activated by high-intensity exercisein young, healthy volunteers.

Erickson is trying to parse the specifics with a study that will assess theeffect of exercise volume on brain aging. Researchers will measure inflammation, signaling molecules, body composition and other markers, as well as mental acuity, on more than 600 volunteers ages 65 to 80, both before and after a year of exercise. Some of the volunteers will do 150 minutes per week of supervised moderate exercise, others will do 225 minutes per week, while a third group will do light stretching instead.

Of course, even after the results of these and other forthcoming trials are in, the right amount of exercise for a particular person is likely to depend on their individual circumstances. For someone with diabetes who wants to improve blood-sugar control, even 10 minutes is probably great, says Barnes. But for cardiovascular risk or brain health, that may be different.

Bamman agrees. Theres not a single organ system in the body that isnt affected by exercise, he says. Part of the reason the effect of exercise is so consistent and so robust is that there isnt a single molecular pathway its going to be a combination of all these things. So at the end of all these trials, were going to look back and list off not just one or two mechanisms, but a number of them. Its going to be a complicated answer in the end.

If exercise is good medicine, how do researchers in the field dose themselves?Knowableasked the experts about their own exercise regimens.

K. Sreekumaran Nair, Mayo Clinic:For many of my diabetic patients, I recommend three days per week of high-intensity aerobic exercise and two days of weight training, with the other two days to do walking. But myself, I do 5 days of high-intensity interval training. And every day I do one kind of resistance exercise: leg press, chest press

Michael Joyner, Mayo Clinic:Forty-five to 60 minutes every morning. I do alternate days biking with intervals one day and a strength circuit the next day. I ride my bike to work 100 to 150 days per year. We just moved near a small lake and I have been swimming across it and back (about a mile) three to four times per week. That will stop when it gets cold.

Jill Barnes, University of WisconsinMadison:Six days a week, movement in the morning (usually yoga, 10 to 60 minutes). Five days a week, cardio in the evening (cycling, running, paddling, hiking at a moderate pace) 25 to 80 minutes. One to two days a week, strength training in the evening, 10 to 25 minutes."

Marcas Bamman, University of Alabama, Birmingham:I exercise five days per week, and sometimes six. I exercise at a pretty high intensity and combine resistance and endurance training.

Kirk Erickson, University of Pittsburgh:I run regularly, usually four to five times per week, and also do some strength training exercises. I have also played squash for many years.

10.1146/knowable-121919-1

Bob Holmesis a science writer based in Edmonton, Canada.

This article originally appeared in Knowable Magazine, an independent journalistic endeavor from Annual Reviews.

Read more here:
Why Exercise is the Real Miracle Drug - Discover Magazine

In 1979, Danish anthropologist Peter Aaby, in his mid-30s, was studying malnutrition in the small West African country of Guinea-Bissau when the outbreak hita measles epidemic of horrific proportions. At least 20 percent of children under 5 years old who got measles that year would die. He and his colleagues began vaccinating, hoping to save the remaining healthy children.

His teams effort would lead to a remarkable discovery: The vaccinated children, about 1,500 of them, didnt dienot from measles or any other condition. In a year, the kids mortality rate for all causes declined threefold compared to unvaccinated children. This is strange, he began to think. Something incredible happened here.

Decades of research and hundreds of studies later, Aaby and a growing community of scientists now hypothesize that some vaccines may help children fight more illnesses beyond the target infection. Your immune system is so smartits just like a brain, explains Christine Stabell Benn, a professor of global health at the University of Southern Denmark, and Aabys partner both in life and in research. It learns something from the event [of getting a vaccine] that it can use in other situations. The pair have observed this knock-on effect in children in Guinea-Bissau whove gotten vaccines for tuberculosis (BCG), smallpox, and polio.

Other research has detected similar results, called nonspecific effects. In a 2015 meta-study, researchers analyzed hundreds of thousands of hospitalizations in Spain that occurred between 1992 and 2011 and found that 10- to 14-year-olds who had received the BCG vaccine at birth saw nearly 70 percent fewer hospital visits due to non-tuberculosis infections than those who had not. In 2018, a study of more than 3,000 hospitalized adults in New Zealand showed that having previously gotten the flu shot decreased the severity of illness and hospitalization time for people who ultimately contracted the flueven for strains they hadnt been protected against. The average vaccinated patient, the study found, spent four fewer days in the ICU for flu-related infections than their unvaccinated counterparts. (The flu vaccine also reduces your risk of hospitalization in the first place.) And in 2019, a small study led by researchers in England suggested that the typhoid vaccine, made with a weakened form of salmonella, might also help combat the flu by giving the immune system a boost to fight other pathogens.

The exact mechanisms behind these unintended positive effects arent fully understood. One clue is that the vaccines that show off-target benefits are in most cases live, meaning they contain an active version of a pathogen in a weakened state. (Most flu shots given in the United States are not live.) In 2012, researchers published a landmark study that revealed how some nonspecific effects might work. As Mihai Netea, a professor at Radboud University in the Netherlands and an author of the study, describes it, when you receive a live vaccine for a disease, certain cells in your body bookmark in their DNA the instructions for fighting it. Next time you encounter the pathogen, or one like it, they know exactly where to open the book, he says.

But research on the nonspecific effects of vaccines is controversialin part because of concerns about the way Aaby and Stabell Benn conducted their initial studies. For example, the children in Guinea-Bissau most likely to receive a measles vaccine, which is administered as early as 12 months of age, were probably healthier to begin with, since parents were unlikely to bring a sick child to receive a live measles vaccine. Other studies by Aaby and Stabell Benn have shown negative outcomes of vaccines: In the developing world, childrenespecially girlswho receive standard, nonlive vaccines for tetanus and polio are more likely to die from any cause than their unvaccinated peers, according to their research. Its unclear whyand the evidence is limited.

Stabell Benn believes that switching to a live vaccine could eliminate many of those negative effects. In a 2019 TEDx talk, she argued that a simple change to the World Health Organization vaccination sequence to emphasize live vaccines over nonlive ones could save more than a million children every year in the developing world. While live vaccines do come with some problemsvery rarely, they can cause a person to contract a form of the disease that theyre supposed to preventshe believes the benefits far outweigh the risks. But in 2016, a group of experts commissioned by WHO analyzed existing studies on the nonspecific effects of vaccines and recommended no change in the sequence of live versus nonlive vaccinesthough they noted the data raise sufficient concerns and they strongly recommend further studies.

While experts admit that no one fully understands how immunizations activate our natural defenses, many scientists are optimistic about the potential of vaccines, especially the live kind. Netea believes they might even be able to rewire the immune system to fight all sorts of conditions, including allergies and cancers. Live vaccines may also hold the secret to making current ones more effective. As I see it, Stabell Benn says, we have a wonderful toolbox with the vaccines.

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40 Years Ago, Doctors Vaccinated a Group of Children in Africa. Then Something Incredible Happened. - Mother Jones

By Glenn Ellis

According to the statistics, somewhere between 5 and 20 percent of those reading this column will get the flu this season. The actual average of those who get it is 8 percent. The numbers get higher because some of us get the flu, but never realize that the reason we feel lousy is because we have the flu.

I hope you dont have media fatigue from hearing about the flu all the time, because this is serious business, and could be a health tragedy for you or for someone you love. Depending on the severity of strain of the flu virus, each year the flu kills anywhere from 3,000 to 49,000 people in the U.S. and sends about 200,000 to the hospital. So, dont make the mistake of thinking a bad cold and the flu are the same thing.

When most of us think of the flu, we tend to think of a sore throat, runny nose, cough, body aches, fever and all those other nasty flu symptoms. What you may not realize is that, for people who are less than healthy to start with, the flu can trigger some other serious medical problems: complications as severe as heart attack and stroke.

My biggest personal reason for being an advocate of the flu vaccine is simple: I care about the vulnerable people around us: the elderly; children; cancer patients; people with weakened immune systems.

Even though the sickest among us suffer the greatest consequence from the flu, it is healthy people who need to get vaccinated. The people we come in contact with on a regular basis, who are really healthy, can be just mildly sick from the flu, but theyre the ones who are moving the flu around the community infecting those whose health is far more vulnerable.

Those whose immune systems are compromised are far more vulnerable to infections secondary to the flu. A cancer patients ability to fight infection is hampered by not only their disease but also by treatments, such as chemotherapy, that weaken their immune system. This means that the flu can lead to complications like pneumonia and delays in life-saving treatments for diseases such as cancer.

The underdeveloped immune system of younger children and infants also puts them at greater risk of the flu and ensuing complications. Same goes for pregnant women who experience changes to their immune system, heart and lungs that make them more vulnerable and lead to complications such as premature labor, preterm birth or birth defects in their unborn children.

No one really knows why the flu season happens when or where, but its happening right now.

Flu season has come early this year due to a strain of the virus not typically seen during this time of year, according to the Centers for Disease Control and Prevention (CDC). The early activity is primarily being caused by influenza B/Victoria viruses, which is unusual this early in the season. It typically hits in late February or March.

While seasonal influenza (flu) viruses are detected year-round in the United States, flu viruses are most common during the fall and winter. Experts are able to determine that the flu season is underway when there is a significant increase in the number of cases turning up at doctors offices for three consecutive weeks.

I am well aware of the decades of controversy surrounding the flu vaccine. I am also aware of how many of us have no idea what the logic is around the vaccine, or how it works.

Flu vaccines protect against three or four types of flu virus (usually 2 A types and 1 or 2 B types). Vaccine manufacturers produce flu vaccines based on the World Health Organizations (WHO) recommendations. In February each year, the WHO assesses the strains of flu virus that are most likely to be circulating in the northern hemisphere over the following winter. Based on this assessment, WHO recommends which flu strains the vaccines should contain for the forthcoming winter.

The flu vaccine stimulates your bodys immune system to make antibodies to attack the flu virus. Antibodies are proteins that recognize and fight off germs, such as viruses, that have invaded your blood.

If youre exposed to the flu virus after you have had the flu vaccine, your immune system will recognize the virus and immediately produce antibodies to fight it. It may take 10 to 14 days for your immunity to build up fully after you have had the flu vaccine. This is why you must ignore those who say they only got the flu after they receive a flu shot. Apparently, they were already infected with the virus when they got the vaccine, but they got sick before the vaccine had a chance to kick in.

Oh, and by the way, you need to have a flu vaccination every year as the antibodies that protect you from flu decline over time, and flu strains can also change from year to year.

Regardless of your religious beliefs; your philosophical position; or your thoughts about conspiracies, the best way to prevent flu is by getting a flu vaccine each year. It is not too late to get vaccinated. As my friend, bioethicist Dr. September Williams states, Remember you do not know how vulnerable the person next to you may be to your slight response to the flu.

Glenn Ellis, is Research Bioethics Fellow at Harvard Medical School and author of Which Doctor?, and Information is the Best Medicine. For more good health information visit: http://www.glennellis.com.

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Ellis: The Worst is Yet to Come this Flu Season - Birmingham Times

People take part in a pro-democracy protest in Hong Kong on Sept. 29. Adryel Talamantes/NurPhoto via Getty Images

Its become fashionable to wonder whether the liberal international order can survive the malign forces that have been lining up against it during the 2010swhat the Wall Street Journal called the Decade of Disruption.But based on recent trends, its a fair bet that democracy, globalism, and open trade will endure handily into the third decade of the 21st century.

Start with the state of democracy. Nothing has been more alarming to internationalists than the one-two punch of U.S. President Donald Trump and British Prime Minister Boris Johnson, who have taken power in two of the worlds oldest and most important democracies by awakening the old demons of nationalism. With Trump focusing his ire on NATO and the World Trade Organization, and Johnson stalking out of the European Union, the two leaders have transformed the once-hallowed special relationship from a bulwark of global stability (sullied though it was by the Iraq War) into what looks more like a wrecking ball. Elsewhere, illiberalism has overtaken young democracies, such as Hungary and Poland, and even threatened mature ones with the rapid rise of nationalist parties such as the Alternative for Germany and Norbert Hofers anti-immigrant Freedom Party of Austria. In the worlds largest democracy, India, Prime Minister Narendra Modi and his Hindu nationalist Bharatiya Janata Party appear to be sending the same message. And there are considerable doubts about whether the democratic body politic possesses an immune system strong enough to fight off a plague of cyber-generated misinformation and disinformation, and systemic hacking by such autocrats as Russian President Vladimir Putin.

But democracy just wont give up, and in 2019which could justly be called the year of global protestit kept reinventing itself at the grassroots. This has been happening in the most unlikely of places around the globe, in countries such as Iran, Lebanon, Iraq, Chile, and above all in Hong Kong, where thousands of determined protesters have braved bullets and tear gas, embarrassing Chinese President Xi Jinping even as he brutally consolidates his autocratic rule on the mainland. Perhaps the U.S. and British democracies are becoming decadentand 2020 will tell us a lot about that question come Novemberbut the idea of democracy remains a powerful, ever-replenishing urge that, as sociologists and political scientists have long told us, only gets stronger the more that income and educational levels increase around the world.

The international economy is also undergoing some severe stress testsand surviving remarkably intact. The year 2019 began with deep-seated fears that Trumps trade wars would help trigger a global recessionand among the most concerned was Federal Reserve Chairman Jerome Powell, who midway through the year suggested he and other central bank chiefs simply didnt know how bad things could get. The thing is, Powell said, there isnt a lot of experience in responding to global trade tensions. Growth and investment are still slowing due in large part to the uncertainty Trump has created, but fears of a recession have receded. It turns out the U.S. president cannot single-handedly return the United States to the days of Smoot-Hawleyeven his fellow neonationalist Boris Johnson believes in free tradeand the domino effect of retaliatory tariffs that followed in the 1930s, setting the stage for world war. (In June 1930, under the Smoot-Hawley Act, the United States raised tariffs to an average of 59 percent on more than 25,000 imports; just about every other nation reacted in tit-for-tat protectionist fashion, severely depressing the global economy.)

Today, the complexities of a deeply integrated global economy and its supply chains may prove too much to undoeven for the most powerful person on the planet.

And what of the institutions of the international system? The United States has always had an uneasy relationship with its post-World War II progeny, principally the United Nations, the WTO, and NATOdespite helping create themand Trump only gave expression to an American id that was long seething under the surface. True, Trump is demeaning these institutions to an unprecedented degree and demanding far more of them. But hes only saying more stridently what was said by, say, President Barack Obama, who also criticized the NATO allies for being free-riders, and former President George W. Bush, whose administration privately mocked the alliance and sneered at the U.N. (Another little-remembered precursor to Trump was President Bill Clintons feisty first-term trade representative, Mickey Kantor, who once said he wasnt interested in free-trade theology and preferred that Americans behave like mercantilists.)

Trump is making a serious run at denuding the WTO by taking down its appellate court, but even that institution is likely to outlast a 73-year-old president who, at most, has only four more years in office to wreak havoc on the global system. This is especially likely because he is now mostly alone in his anti-globalist passion with the departure of his deeply ideological national security advisor, the militant John Bolton.

Lets not forget either that the advent of Trump and Johnson represents a legitimate backlash to major policy errors made by the elites who have dominated the international system. George W. Bush led the Republican Party badly astray with his strategically disastrous Iraq War and fecklessness over the deregulation of Wall Street, which set the stage for the biggest financial crash since 1929 and the Great Recession. That turned voters off to traditional Republican thinking and opened the door to Trumps unlikely takeover of the party. Something similar happened in Britain, when Bushs partner in these neoliberal economic delusions and his ally in an unnecessary war, the once-popular Labour leader Tony Blair, set the stage for Labours eventual handoff to the socialist Jeremy Corbyn. (A shift that was, in turn, analogous to the ascent of Sen. Bernie Sanders, Sen. Elizabeth Warren, and the left inside the U.S. Democratic Party in response to the rise of Trumps 2016 presidential rival Hillary Clinton, who was seen as pro-war and too friendly to Wall Street.)

But the larger point is that Trump and Johnson are only the latest stresses to a system that, since the end of the Cold War, has suffered some pretty major ones and yet endured. In the quarter-century since then, financial markets collapsed several times, and the global economy has remained intact. Islamist terrorists have struck at major capitals around the world, and a clash of civilizations hasnt ensued. The worlds two largest economies, the United States and China, incessantly bicker, but theyre still doing business. Ivory tower realists continue to be dead wrong in their predictions that the international system will fall back into anarchy, even when politicians like Trump are doing their best to make that happen. On the realist view, the so-called West and its institutions should have disintegrated after the Cold War with the disappearance of the Soviet Union; as Owen Harries wrote in Foreign Affairs in 1993, The political West is not a natural construct but a highly artificial one. It took the presence of a life-threatening, overtly hostile East to bring it into existence and to maintain its unity. It is extremely doubtful whether it can now survive the disappearance of that enemy.

Instead, these international constructs only expandedso rapidly and intensively that they generated a backlash. And that expansion is plainly still outpacing the efforts to block or destroy it, especially as we see other nations forging free trade deals behind Trumps back. Above all, while plainly Americas stature as stabilizer of the international system has been seriously set backfirst by Bush, most recently by Trumpthere is some positive news even in the impeachment drama now underway. Although Trump is all but certain to be acquitted in the Senate, the impeachment vote in the House, following weeks of testimony by career U.S. diplomats, was a dramatic reaffirmation of traditional American values for fair dealing not just with Ukraine, but with all nations.

Perhaps, for now, that will be enough to keep things intact.

See the article here:
Why the Liberal International OrderFree Trade, Democracy, and GlobalismWill Survive the 2020s and Donald Trump - Foreign Policy

Alice Dreger

Alice Dreger is an historian of medicine and science, a sex researcher, an award-winning writer, and an (im)patient advocate. Dregers latest major work is Galileos Middle Finger: Heretics, Activists, and the Search for Justice in Science.

ALICE DREGER: We don't actually know the extent to which gender is socially constructed because you can't do an experiment where you remove culture and see what happens. So we don't know to what extent what we see as gendered patterns are the result of sex, biological sex, males and females. We know that gender differs according to culture, but we also know that there are patterns that appear to be fairly universal in terms of gender norms. And the ones that are more universal are more likely to probably have a sex bases to it, an evolved-to-sex basis, that is to say biological basis for males and females. So, for example, which gender serves a very important meal may be different by different cultures. So in some cultures a man will serve a very important meal versus a woman. So for example, think about it in the United States that historically speaking the father carves the turkey on Thanksgiving, but in general women prepare food historically speaking. So what we know is that these kinds of things can differ by culture, but that there are some "universals". And one of the universals we find, for example, is in childhood play that we find that children who are girls tend to do more social play, they tend to do more social role-play. Children who are boys tend to do more competitive play, they tend to do more play that mimics aggression or that mimics sport and mimics sometimes building, and so there are these kinds of patterns. But that doesn't mean everybody fits them.

And it's really interesting actually too if you look cross-culturally scientists find evidence that this may have it's not just gender, that there's a sexuality component to it too. So boys who are going to grow up and be gay, and we know who they are because of retrospectively they grow up to be gay, they're what's called androphilic, that is to say they're attracted to males. And the majority of females are also attracted to males, so most females are androphilic and a small percentage of boys will grow up to be androphilic. We know that historically speaking, cross-culturally they tend to be more feminine in terms of their interests, they're more interested in social role-play, for example, they're more interested in helping their mothers, they're more interested in associating with girls as young children and more interested in dressing as girls, for example. That doesn't mean that they are girls, but it does suggest to us that sexuality and gender have interplayed components in them, that gender isn't just about social role but it has something to do with sexuality and that there's a reason females end up with these kind of patterns and males end up with these kinds of patterns and when you have a male who's attracted to males he ends up with a little bit more of the female pattern and in some circumstances if you have a girl and she's attracted to girls she'll end up with a little bit more of the male pattern in childhood.

So gender and sexual orientation seem to have sort of some connection to each other, but it's not a perfect connection in terms of absolute correlation and so we can't say that we can easily predict what would be somebody's gender role or sexual orientation simply by looking at some of the components.

Evolution would naturally favor heterosexuality because that's how you get babies. And so if we're thinking about genes trying to produce genes it would make no sense to have genes that would lead to people who don't reproduce, because those genes would not be reproduced. That said, we know cross-culturally gay people exist. So we know that that's a natural variation in the population. And so then scientists ask the really interesting question, why is that there? Why does that not disappear over time? Because at least in theory that should lead to lower reproductive fitness, which means it should lead to fewer babies, and so it should fade out evolutionarily speaking. One possibility is that it's a side effect, that human variation is good for the species and so evolution is responding to the situation not by reducing necessarily everything that doesn't work, but saying "Let's keep throwing up variation, and some of it will work in some environments and some of it will work in other environments." Being a varied species makes a species more resilient.

So it may be the case that being gay if you're born that way is just a variation on a theme and it will show up every now and then just because variations show up. But some scientists find some evidence that there may actually be advantages to a family of having a certain percentage of the children be gay. And this is work done, for example, by Paul Vasey at the University of Lethbridge. And he's been looking at the population in Samoa as well as other places, but Samoa as a cultural system that actually recognizes that a certain percentage of the boys are going to grow up to be androphilic, they're going to be interested in men sexually. And they actually have a whole cultural system for it. They have a third gender category called the fa'afafine and when a boy it becomes evident is that kind of boy the child is raised as a girl and becomes a woman culturally speaking but that doesn't change her body at all but partners with men. So in our culture that would be called transgenderism, but in this culture it's a third gender category that absorbs what in our culture might just turn out to be gay men. And what Paul has found is that when he looks at the families that have fa'afafine within them the fa'afafine are not using up a lot of resources, because they're not themselves having childrenthese are big-family culturesbut they do take their own earnings and they direct it at their nieces and nephews. And that means you have more adults producing more resources for a smaller number of children. So biologically there may be an advantage for families to have a certain number of gay children, because those people will not reproduce but they will take care of the nieces and nephews. And so overall the population, the genetics of a family will be continued on because that family has a genetic advantage.

And when you think about it we have this sort of stereotype of the gay uncle who takes care of the nieces and nephews in terms of providing for them and providing extra resources, and they're not spending it on their own kids, they're spending it on their sister's and brother's children, that might be a possible evolutionary explanation for why it is that we see homosexuality persist in the human system. It's also the case, we know from work done by Ray Blanchard in Canada, that a certain number of men who will grow up to be gay get that way not through genetics per se, but they get that way in the womb. So it's inborn but not genetic. And what happens is apparently well we know statistically from huge studies now if a mother has lots of pregnancies of males every successive male will be a little bit more likely to be gay. So the farther down you go in that sibling chain the more likely it is that the later-born males will be gay. This has been studied in many populations in the world, large numbers, and it's rigorous. We know that this is true. So why would that be? Well, it looks like it's a kind of side effect: the mother's immune system appears to be reacting to male hormones and maybe dampening them down a little bit, and this results in something called the fraternal birth order effect, which is that later born males are more likely to be gay. It's a surprising finding because it suggests to us that some men are absolutely born gay but not because of genetics, they're born gay because of the birth order in terms of some sort of effect having on a woman's system, which is reacting to her children's system, and it only occurs in males, it doesn't occur in females. And that's part of the reason why the theory is it's an immune response because it doesn't occur with females it only occurs with males born out of the same womb. So that's something I've colloquially called womb-gay, but it's called the fraternal birth order effect. And I think the evidence is very strong that a certain percentage of gay people are born that way. We do not have good evidence that straight people are born that way. We don't bother to look for that evidence. Straight people have been less interesting to scientists than gay people in terms of where they come from. And that's because there's a heterosexist assumption that straight people "require no explanation" and gay people "require explanation."

I mean in terms of evolution gay people do require an explanation. Logically speaking we should say "Well that's not a very 'successful strategy,'" as it's called in science, it doesn't lead to a higher reproductive fitness meaning it doesn't lead to more babies. So logically you would want to explain gay people. But it's also a political issue that basically straight people have required no explanation and gay people have required explanation. And some of the explanations historically have been rather unpleasant, like blaming mothers who are frigid or overly clingy in the case of being gay"over clingy mothers make gay boys." What we know from cross-cultural studies is that gay boys are more interested in being with their mothers than straight boys, and so it's not that the mothers are more clingy it's that the boys are more tolerant of time with their mothers.So we've studied much more about gay people that we have studied about straight people, and straight people remain largely a mystery as to how they operate. What makes them straight? We don't really know. We also don't know why gay people are attracted to each other anymore than we know why straight people are attracted to each other. We have hints about smells and about genetic interactions and about facial symmetry, but we really know very little about why straight people are straight and why gay people are gay.

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#4: What makes someone gay? Science is trying to get it straight. | Top 10 2019 - Big Think

Lose weight, eat less junk food, and stick to a diet top plenty of New Years resolution lists, but many experts say that these goals may set unrealistic expectations and set you up for failure before February even hits. Instead, doctors and registered dietician say that a more sustainable approach to managing weight, feeling good, and changing eating habits is to focus on identifying which foods nourish your body and give you the proper fuel you need to live a great life. So to jumpstart 2020, we rounded up some of the best products to help you eat well and feel your very best.

[Photo: courtesy of EverlyWell]Find your food sensitivitiesSome foods that are generally considered nutritious may not be good for you specifically, thanks to food sensitivities that can cause headaches, joint pain, fatigue, and digestive issues. To identify which foods might be the culprits, you can start elimination diet test from scratch, which can take months or years to execute properly. You can also jumpstart that process withEverlyWells mail-in food sensitivity test($159), which requires just a small sample of blood. The tests, which are reviewed and approved by independent board-certified physicians, measure IgG antibodies in your bloodstream when exposed to certain foods and ingredients. (Its important to note that this test is merely for food sensitivities, not more serious food allergies, nor can it identify is someone is lactose intolerant.) You can then use your test results to start a guided elimination diet.

[Photo: courtesy of Peter Pauper Press]Keep a food journalResearch shows that for people interested in learning more about healthy eating habits, keeping a journal is very effective tool. During onestudyof nearly 1,700 participants, those who kept daily food records lost twice as much weight as those who kept no records. Additionally, a food loglike this handy, self-guidedDaily Food Journal ($8)is crucial in helping to identify eating patterns and certain foods that dont make you feel good or cause bloating, digestive issues, headaches, and the like. If youre going to try an elimination diet, a food journal is key. The only time we wouldnt recommend using a food log is if you aresusceptible to obsessive eating patterns or food phobias; have a history of an eating disorder; or, if for any reason, a food log makes you feel guilt, shame, or fear. If thats the case, skip this step. Because keeping track of what you eat should make you feel mindfulnot bad about yourself.

[Photo: courtesy of Seedlip]Skip the boozeRegardless of how much (or little) you drink, anyone can all benefit from cutting back on alcohol, since consumption is linked to increased risk of cancer, heart disease, immunity issues, weight gain, muscle loss, and a slew of other not-so-fun side effects. But that doesnt mean your dry January needs to be joyless. The botanical spirits of nonalcoholic distillery Seedlip has become a hit with high-end mixologists. Now you can try them at home with theSeedlip Distilled Non-Alcoholic Spirits Sampler ($107.50, set of 3). With only three ingredients (water, natural botanical distillates, and citric acid), these spirits are good for your health and surprisingly enjoyable for the palate. Beer lovers also have more alcohol-free options available to them, such asWellbeing Brew Cosnon-alcoholic craft beer($12), which only has 68 calories and contains zero grams of sugar. You can also try the award-winningnonalcoholic brews($12) of the breakout Athletic Brewing Company.

[Photo: courtesy of Sun Basket]But dont skip mealsSkipping meals is a bad ideathat can spike your blood sugars and lead to overeating laterand wreak havoc on your metabolism and immune system. If you find youre simply too busy to shop for and cook your own meals and you want to avoid eating unhealthily on the run, consider a subscriptions service like the Sun Basket meal kit($11.99 per serving for 2 people, $10.99 per serving for 4 people, regardless of frequency), which brings you a weekly box of organic and non-GMO ingredients to prepare your own meat-free or vegan meals. For people who are even more pressed for time,Sakara(starting at $239/week) delivers fresh meals, teas, and supplements that are completely organic, plant-based, gluten-free, dairy-free, non-GMO, and contain no refined sugar. No prep or cooking required.

Looking for more goodies and gadgets? Check out our handpicked suggestions.

Fast Companymay receive revenue for some links to products on our site.

Read more:
2020 New Year's resolution: How to eat better and master your nutrition - Fast Company

Megan Sheppard offers some natural health advice.

Q: Following recent surgery, I picked up a superbug called CPE and needed to be isolated in hospital for some weeks. I still have traces of the bug in my system. What would you advise?

A: CPE, or Carbapenemase-Producing Enterobacterales, is the latest in a long line of so-called superbugs which have developed a resistance to nearly all known prescription antibiotics.

These pose a particular threat to high-risk patients, such as those in intensive care, undergoing bone marrow and organ transplants, receiving cancer treatments, and people who require major surgery.

There are two bee products which have had great results in treating patients with the other well-known superbug, MRSA (Methicillin-resistant Staphylococcus aureus) one of which is manuka honey.

ManukaCare 18+ from Comvita is rated at a minimum potency of UMF 18, which means that it is equivalent to at least an 18% phenol solution four times greater than standard antiseptics.

Take a teaspoon of honey straight from the spoon once in the morning and again in the evening.

The other bee product with potent antibacterial properties is propolis. Used since the 1960s to fight bacterial infection, including against MRSA, its unique as it also has antiviral, antifungal, anti-inflammatory, anti-cancer and immunomodulatory effects.

Propolis alters the management of cytokine production and release in our immune system, allowing the body to quickly respond to antigens. Cytokines are basically chemical messengers which enable cells in our immune system to communicate with each other.

Additionally, propolis contains bioflavanoids which stimulate interferon production, keeping your body in a fit state to fight off infection and remain in a state of health. Propolis liquid costs 8.34 for 30ml and is available from health stores take as directed.

Q: My periods have become irregular. When they eventually arrive, sometimes skipping a month, the flow is very heavy. Im 43 years old. Is there a natural remedy I could take?

A: This sounds very much like you have entered the perimenopausal stage of your journey as a woman. These pre-menopausal changes typically begin anywhere from the age of 35 years onwards.

The wonderful Andean root, maca (Lepidium meyenii) will not only help to bring your cycle closer to the 28-day ideal, but it also works to increase energy levels, improve mood, and is a powerful antioxidant.

Maca is also a complete protein and high in many vitamins and minerals, including calcium and zinc.

Agnus castus (also known as Vitex, Monks Pepper, or Chasteberry) is a wonderful herb for regulating the menstrual cycle.

It can also help with extreme period pains, heavy bleeding, intermittent bleeding, shortened cycle, infrequent menstruation, cystic hyperplasia of the endometrium, secondary amenorrhoea.

Agnus castus is best taken once daily following breakfast; improvements can appear relatively quickly, but treatment should be continued for a minimum of six months for long-lasting results.

If you are taking a tincture preparation (typically 1:5 strength), then you will need to take 1-3ml (20-60 drops) each morning. Capsules should be taken at a dosage of 500-1,000mg daily.

There are so many valuable herbs to help with perimenopausal and menopausal symptoms: red clover, dong quai, black cohosh, wild yam, raspberry leaf, squaw vine, and nettle (leaf and root).

You can do your own research as to which of these seems to fit you best or find a combination formula as many of these herbs work even more effectively when combined synergistically.

It is important to make sure you are supporting your adrenal system and keeping on top of your stress levels.

Eating clean whole foods, exercising regularly, breathwork and meditation, drinking plenty of water, and making time to do the things you love are all important for your mental and emotional wellbeing as well as helping to regulate your menstrual cycle.

NOTE: The information contained in this column is not a subsitute for medical advice. Always consult a doctor.

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Natural Health: 'I still have traces of a superbug in my system. What would you advise?' - Irish Examiner

The biggest gains from these new tools have been in the treatment of melanoma, the cancer Australians suffer from more than anybody else, and non-small-cell lung cancer, the cancer that kills more Australians than any other.

Says Darren Saunders, a UNSW cancer researcher: "The way my clinical colleagues describe it to me is (that it's) the biggest transformation in the way we treat cancer in their careers."

"Without immunotherapy, I'd be a dead man": Warren Penna has seen promising results for the treatment of his melanoma. Credit:Chris Hopkins

It has made an enormous difference to patients who might otherwise have given up hope.

Warren Penna first noticed something was amiss when a large freckle on his right shoulder started to change shape. Then it darkened and began to bleed. The retired horticulturist went to a number of specialists before he was finally diagnosed with melanoma in 2014.

He had the cancer removed from his shoulder at The Alfred, but earlier this year, the 54-year-old Footscray man was diagnosed with throat cancer. As specialists conducted scans of his body, they discovered melanoma tumours in his lungs, liver, armpit and brain.

"When I saw the scans I was certain a dead man," Mr Penna said.

Doctors decided to target the melanoma first and the last eight months have been a blur of radiation treatments and surgery.

But it is the immunotherapy that Mr Penna is undergoing at Peter MacCallum, which involves fortnightly injections of antibodies Nivolumab and Ipilimumab, that has garnered the most remarkable results.

In a matter of months, the largest tumour in his lung has shrunk from 4.5 centimetres to 2 centimetres and specialists remain optimistic. His immunotherapy treatment will continue until mid 2022.

"It can be really tough at times because you are constantly thinking about your own mortality," Mr Penna said.

"But I feel so incredibly grateful I am able to get this treatment here in Australia and that is available on the Pharmaceutical Benefits Scheme, because I have no doubt I would be dead right now without it."

Immunotherapy is known for its severe side-effects and Mr Penna, who is also due to start radiation next week for his throat cancer, struggles with overwhelming fatigue and sometimes breaks out in a rash.

"I count myself very lucky though because so many others have really significant side-effects like diarrhoea and nausea," he said.

Cancer develops when a normal cells DNA mutates; often this is because it was exposed to a carcinogen like sunlight, but sometimes there is no cause at all. Just bad luck.

Our immune system is designed to sniff out and kill these mutated cells, but sometimes, the DNA mutation changes the cell in a way that makes it invisible to our immune system. Unchecked, the cell multiplies into a lethal tumour.

For the past 200 years, our treatments for cancer have been crude: surgery to remove the tumour; radiation to kill it; and broad poisons that kill the cancer but often the patient as well.

And then, almost overnight, everything changed.

In the '80s and 90s, scientists discovered immune checkpoints, tiny molecular flags that cells run up to mark them as friendly, so the immune system does not kill them.

They then discovered some cancers were covered in these flags, making them completely invisible to the immune system.

What if, the scientists thought, you could get rid of those flags?

"Initially, people were pretty sceptical of this idea. It was pretty unpopular," says Professor Doug Hilton, head of the blood cancer lab at the Walter and Eliza Hall Institute.

Independently, other labs had developed monoclonal antibodies. These are human immune molecules, made by cloned human immune cells living in a laboratory dish and specifically engineered to stick to a certain part of a cell.

With a tweak, the antibodies could gum over the checkpoints on cancer cells. Suddenly, they were visible to the immune system, which killed them.

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The first immune checkpoint inhibitor, the skin cancer drug Yervoy, was approved in Australia in 2011. Lung cancer drug Keytruda which Professor Hilton labels as one of the most important cancer medicines of the decade was approved four years later, and came on the Pharmaceutical Benefits Scheme at the start of December 2019.

"They have been absolutely transformative," says Professor Thomas.

A 2015 review of clinical trials of Yervoy for melanoma found more than 20 per cent of those treated were alive 10 years later and showing no sign of the disease. Before the treatment, the long-term survival rate was less than 10 per cent.

Keytruda treatment has led to complete remission for 22 per cent of patients with Hodgkins lymphoma in one clinical trial; in another, it cut risk of death by 40 per cent compared to conventional chemotherapy.

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Importantly, the effect of the checkpoint inhibitors appears long-term. Even after therapy stops, the immune system is still capable of spotting and killing any new cancers that arise.

"It appears to be a cure for some individuals," says Professor Thomas.

In 2011, as everyone was celebrating Yervoys success, word started to filter out about remarkable results in Philadelphia.

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An American team had completely cured a seven-year-old of a lethal childhood cancer leukaemia, using a new treatment called CAR-T.

That child, Emily Whitehead, is now 14. The cancer has not returned.

CAR-T works in reverse to checkpoint inhibitor therapy. A patients own immune cells are drawn from the blood and placed in a test tube.

A genetically modified virus is used to edit the DNA of those immune cells, giving them the ability to seek and kill the patients tumour.

When CAR-T works, it works extraordinarily well. One clinical trial led to the complete eradication of cancer in more than half the study participants.

Most excitingly, if the technique works, it could be used for almost any form of cancer. All the doctors would need to do is to tweak the T cells DNA to target the cancer in question.

The challenge, says Dr Saunders? "At the moment it costs half a million dollars per patient."

This is the next step. Bringing down the cost of immunotherapy, while also continuing clinical trials to see what other cancers it will work on.

But for the first time, a durable cure for cancer actually seems within our grasp.

Liam is The Age and Sydney Morning Herald's science reporter

Melissa Cunningham is The Age's health reporter.

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'Scarily like a cure': the decade that revolutionised our fight with cancer - The Age

I'm hesitant to give my child the measles vaccine, because I'm worried about long-lasting side effects. Is it dangerous? Sally G., Jacksonville, Florida

As we've said before, it's smart to get your child the vaccine as early as your pediatrician recommends. The risk of getting vaccinated is greatly outweighed by the benefit of avoiding the measles. For vaccinations overall, the ratio of risk to benefit is one to 40,000. Worldwide, the measles kills over 100,000 children annually. In the U.S., since Jan. 1, there have been 880 cases of the disease, which was declared eradicated here in 2000! The real news, however, is that the re-emergence of measles poses a greater risk than we knew.

Harvard researchers have found that measles causes immune amnesia. It wipes out 20% to 50% of your body's antibodies, which are protecting you from a slew of diseases caused by other viruses and bacteria. That may be why bacterial ear infections and pneumonia are common complications after getting the measles. Long-term effects may be even more serious. And that's another good reason to get your child vaccinated as early as recommended.

So why are so many American parents hesitant? Researchers at Brigham Young University thought it may be because folks don't have firsthand experience with the devastating effects of those illnesses. To test the theory, they sent 250 students out to interview locals who had come down with vaccine-preventable diseases, such as polio, shingles and tuberculosis. Some of those students referred to themselves as "vaccine hesitant," but around 70% became pro-vaccine after learning how life-damaging the diseases were.

Bottom line: Don't make yourself go through firsthand tragedy before you realize how smart it is to get vaccinated! Kids should get the MMR (measles, mumps, rubella) vaccine at 1 year old and again between 28 days later and 6 years old. You can also opt for two doses of the MMRV (measles, mumps, rubella, and varicella/chickenpox) vaccine; it's approved for children 12 months through 12 years old.

Last week I thought I heard someone at the door, but when I checked there was no one there. Am I losing my mind, or should I get my hearing checked? Sam B., Portland, Oregon

If you have ringing in your ears, doorbells or otherwise, you might want to get checked out by an audiologist. It could be a sign of hearing loss. But if it's just a one-time event, it's probably nothing.

Sensory hallucinations what that was are pretty common, and there are many forms. You can hear, see, smell, taste or feel something that isn't there. While they can be associated with serious mental disorders such as schizophrenia, they are also related to certain medications, drug abuse, medical conditions like Parkinson's and perhaps sleep deprivation, stress and anxiety.

They can also result from what Georgetown University neuroscientists say is a bottleneck of feed-forward and feedback signals. It's what can occur when the brain is asked to process more information than it can handle. These days, there is more information out there at your fingertips (coming in and going out) than at any time in human history.

In addition, researchers at Stanford University recently discovered how easy it is to provoke hallucinations. In the lab, they altered the neural activity of mice (those rodents have millions of neurons in their brains; humans have billions) by disrupting about 20 individual neurons using light and sound. When they did so, the mice showed signs of believing something was there when it wasn't. This prompted one researcher to ponder, "Why are we not hallucinating all the time, due to spurious random activity?"

Now, that's not to diminish the seriousness of recurrent hallucinatory episodes that interfere with your everyday quality of life. If that's the case, you should keep a journal of when and where they happen and discuss the incidents with your doctor so he/she can pinpoint the cause.

Mehmet Oz, M.D. is host of "The Dr. Oz Show," and Mike Roizen, M.D. is Chief Wellness Officer and Chair of Wellness Institute at Cleveland Clinic. Email your health and wellness questions to Dr. Oz and Dr. Roizen at youdocsdaily@sharecare.com.

Excerpt from:
Oz & Roizen: Measles wipes out parts of the immune system - Bluffton Today

Food allergens are the scourge of the modern school lunchbox. Many foods contain proteins that can set off an oversized immune reaction and one of the fiercest is the humble peanut.

Around 3% of children in Australia have a peanut allergy, and only 1 in 5 of them can expect to outgrow it. For these unlucky people, even trace amounts of peanut can trigger a fatal allergic reaction.

But what sets the peanut apart from other nuts? Why is it so good at being an allergen?

To answer this, we have to explore the pathway from allergen to allergy, and just what it is about an allergen that triggers a response from the immune system.

Read more: What are allergies and why are we getting more of them?

Before coming into contact with the immune system, an allergen in food needs to overcome a series of obstacles. First it needs to pass through the food manufacturing process, and then survive the chemicals and enzymes of the human gut, as well as cross the physical barrier of the intestinal lining.

After achieving all of this, the allergen must still have the identifying features that trigger the immune system to respond.

Many food allergens successfully achieve this, some better than others. This helps us to understand why some food allergies are worse than others.

The most potent allergens like peanuts have many characteristics that successfully allow them to overcome these challenges, while other nuts display these traits to a lesser extent.

The first characteristic many allergenic foods have, especially peanuts, is strength in numbers. Both tree nuts and peanuts contain multiple different allergens. At last count, cashews contain three allergens, almonds have five, walnuts and hazelnuts have 11 each and peanuts are loaded with no less than 17.

Each allergen has a unique shape, so the immune system recognises each one differently. The more allergens contained in a single food, the higher the potency.Additionally, many of these allergens also have numerous binding sites for both antibodies and specialised immune cells, further increasing their potency.

The first hurdle for a food allergen is the food manufacturing process. Many nuts are roasted prior to consumption. For most foods, heating changes the structure of proteins in a way that destroys the parts that trigger an immune response. This makes them far less potent as allergens.

This is not the case for many tree nuts: allergens in almonds, cashews and hazelnuts survived roasting with no loss of potency.

And for the major peanut allergens, its even worse. Roasting actually makes them more potent.

Read more: Can I prevent food allergies in my kids?

From here, the allergen will have to survive destruction by both stomach acid and digestive enzymes within the human gut. Many nut allergens have the ability to evade digestion to some degree.

Some simply have a robust structure, but peanut allergens actively inhibit some of the digestive enzymes of the gut. This helps them safely reach the small intestine, where the allergens then need to cross the gut lining to have contact with the immune system.

This is where peanut allergens really stand apart from most other allergens. They have the ability to cross the intestinal cells that make up the gut lining. Given their relative sizes, this is like a bus squeezing itself through a cat flap.

Peanut allergens accomplish this remarkable feat by altering the bonds that hold the gut cells together. They can also cross the lining by hijacking the guts own ability to move substances. Once across, the allergens will gain access to the immune system, and from there an allergic response is triggered.

The combination of multiple allergens, numerous immune binding sites, heat stability, digestion stability, enzyme blocking, and the effect on the gut lining makes peanut a truly nasty nut.

This leaves us with a nagging question: if peanuts are so potent, why doesnt everyone develop a peanut allergy? We still dont know.

Recently, a potential vaccine developed by researchers from the University of South Australia has shown promise in reprogramming the immune system of mice and blood taken from people with peanut allergy. Will this translate to a potential treatment for peanut allergy? We will have to wait and see.

For now, the more we learn about the action of allergens, and the more we understand their effects on our body, the more we can develop new ways to stop them. And eventually, we might outsmart these clever nuts for good.

Link:
Tough nuts: why peanuts trigger such powerful allergic reactions - The Conversation AU

DetailsCategory: VaccinesPublished on Monday, 16 December 2019 19:29Hits: 279

First allogeneic, off-the-shelf cell therapy approach that enhances T-cell activation through localized OX40-mediated co-stimulation of dormant immune signals

DURHAM, NC, USA I December 16, 2019 IHeat Biologics, Inc. (NASDAQ:HTBX), a clinical-stage biopharmaceutical company specialized in the development of therapeutics designed to activate patients' immune systems against cancer, today announced that the Company has dosed the first patient in the first Phase 1 clinical trial of HS-130, in combination with HS-110, for patients with advanced solid tumors refractory to standard of care.

HS-130 is Heat's allogeneic cell line engineered to locally secrete the extracellular domain of OX40 ligand fusion protein (OX40L-Fc), a key costimulator of T cells, designed to augment antigen-specific CD8+ T cell response. HS-130 was manufactured by utilizing the Company's proprietary process to reprogram a live, genetically modified cancer cell line. In multiple preclinical models, these responses have demonstrated improved efficacy and safety using OX40L-Fc via cell-based delivery compared to systemic delivery of an OX40 agonist antibody in combination with HS-110.

The first-in-human study is expected to enroll up to 30 patients under the supervision of lead investigator Dr. Rachel Sanborn, Director of the Phase 1 Clinical Trials Program at the Earle A. Chiles Research Institute, a division of Providence Cancer Institute in Portland, Oregon. In this study, patients will receive escalating doses of HS-130 in combination with HS-110. The objectives of the study are to evaluate patient safety and to determine the optimal dose for a subsequent Phase 2 trial.

Jeff Wolf, Heat's CEO, commented, "We are pleased to announce the initiation of this combination study, which marks a key milestone for Heat as we advance our latest asset into clinical development. We look forward to sharing clinical proof of concept data to enable the development of a new generation of allogeneic therapy drug candidates in 2020."

About HS-110

HS-110 is designed by engineering gp96-Fc to deliver more than 70 cancer testis antigens to stimulate the patients' immune system and activate a robust cytotoxic T cell response. HS-110 has completed enrollment in a Phase 2 clinical trial for advanced non-small cell lung cancer, in combination with Bristol-Myers Squibb's nivolumab (Opdivo) or with Merck's pembrolizumab (Keytruda) (NCT 02439450).

About HS-130

HS-130 is designed with the same parent cell line as HS-110 but is engineered to secrete OX40L-Fc fusion protein, a potent inducer of antigen-specific CD8+ T cell proliferation. The first-in-human study aims to evaluate the safety and dose-response of HS-130 in combination with HS-110 in patients with advanced solid tumors (NCT04116710).

About Heat Biologics, Inc.

Heat Biologics is a clinical-stage biopharmaceutical company developing novel therapeutics designed to activate a patient's immune system against cancer using CD8+ "Killer" T-cells. Pelican Therapeutics, Inc., a subsidiary of Heat, is focused on the development of co-stimulatory monoclonal antibody and fusion protein-based therapies designed to activate the immune system. For more information, please visit http://www.heatbio.com.

Reference

Fromm G, de Silva S, Giffin L, Xu X, Rose J, Schreiber TH. Gp96-Ig/Costimulator (OX40L, ICOSL, or 4-1BBL) Combination Vaccine Improves T-cell Priming and Enhances Immunity, Memory, and Tumor Elimination. Cancer Immunol Res. 2016 Sep 2;4(9):766-78.

SOURCE: Heat Biologics

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Heat Biologics Announces First Patient Dosed in the First Phase 1 Trial of HS-130 | Vaccines | News Channels - PipelineReview.com

DetailsCategory: DNA RNA and CellsPublished on Monday, 16 December 2019 19:43Hits: 277

CULVER CITY, CA, USA I December 16, 2019 I NantKwest Inc. (Nasdaq: NK), a clinical-stage natural killer cell-based therapeutics company, and ImmunityBio, a privately held immunotherapy company, today announced results from their Phase 1b trial investigating a novel, first-in-human immunotherapy protocol consisting of NantKwests off-the-shelf, antibody-targeted NK cells (haNK) combined with ImmunityBios IL-15 superagonist (N-803), low-dose metronomic chemoradiation therapy, adenoviral and yeast tumor-associated antigen vaccines (MUC1, brachyury, CEA) and a PD-L1 checkpoint inhibitor in patients with metastatic triple negative breast cancer (TNBC) who had relapsed after prior therapy.

The results were presented at the 2019 San Antonio Breast Cancer Symposium (SABCS) on December 13, 2019, in San Antonio, Texas, in a poster titled Safety and efficacy from first-in-human immunotherapy combining NK and T-cell activation with off-the-shelf, antibody-targeted CD16 NK cell line (haNK) in patients with 2nd-line or greater metastatic triple-negative breast cancer (TNBC).

This landmark study is the worlds first trial to combine cellular therapy with checkpoint inhibitors and IL-15 cytokine stimulation, as well as with adenoviral vectors, all acting in concert to induce immune simulation of both NK cells and T cells.

We are extremely pleased that the FDA granted us IND authorization to initiate this novel immunotherapy trial enabling the safety and efficacy study of multiple novel biological agents administered as a single protocol in the outpatient setting, said Dr. Patrick Soon-Shiong, Chairman and CEO of NantKwest. This important trial forms the basis of our approach to induce immunogenic cell death and long-term memory, and avoid the ravages of high dose chemotherapy.

Achieving durable, complete responses in metastatic TNBC patients that have failed all current standards of care is a promising finding and further validates our approach to orchestrate both the innate and adaptive immune system, continued Soon-Shiong. TNBC is a highly aggressive cancer, with limited treatment options and poor prognosis. These results are important proof-of-concept supporting our hypothesis that comprehensively activating the immune responses of the NK, T and Dendritic cells would induce immunogenic cell death leading to durable responses, even among this challenging patient population. We are thrilled with the safety and efficacy data from this first-in-human clinical trial of combination NK cell therapy, cytokine fusion protein, chemoradiation and checkpoint inhibitor, and look forward to advancing this exciting off-the-shelf cell therapy approach to randomized clinical trials in this setting.

Data Highlights Include:

The approximately 10-20% of breast cancer patients who are triple negative are faced with a grim prognosis with limited treatment options. These results are clinically significant, with overall response rates and complete response rates in this highly refractory, advanced metastatic patient population, said Dr. Chaitali Nangia, a Hematologist/Oncologist with the Chan Soon-Shiong Immuno-Oncology Network and study co-author. Importantly, these responses to treatment are also durable, with median progression free survival exceeding 13 months compared to historical controls of approximately 3 months in this heavily pretreated population. We also observed a positive safety and tolerability profile, with no cytokine release syndrome. Taken together, these efficacy and safety results point to the emergence of a new treatment paradigm for TNBC.

About NantKwest

NantKwest (NASDAQ: NK) is an innovative, clinical-stage immunotherapy company focused on harnessing the power of the innate immune system to treat cancer and virally induced infectious diseases. We are the leading producer of clinical dose forms of off-the-shelf Natural Killer (NK) cell therapies. Our activated NK cell platform is designed to destroy cancer and virally infected cells from the body. The safety of our optimized, activated NK cells, as well as their activity against a broad range of cancers, have been tested in phase I clinical trials in Canada and Europe, as well as in multiple phase I and II clinical trials in the United States. By leveraging an integrated and extensive genomics and transcriptomics discovery and development engine, together with a pipeline of multiple, clinical-stage, immuno-oncology programs, NantKwests goal is to transform medicine by delivering living drugs in a bag and bringing novel NK cell-based therapies to routine clinical care. NantKwest is a member of the NantWorks ecosystem of companies. For more information, please visit https://nantkwest.com.

haNK is a registered trademark of NantKwest, Inc.

About ImmunityBio

ImmunityBio is a privately held immunotherapy company with a broad portfolio of biological molecules, including an albumin-linked chemotherapeutic, peptides, fusion proteins, cytokines, monoclonal antibodies, adenovirus, and yeast vaccine therapies.

ImmunityBios oncological goals are two-fold: To employ the companys broad portfolio of biological molecules to activate endogenous NK and CD8+ T cells, and to develop a T cell memory cancer vaccine to combat multiple tumor types without the use of high-dose chemotherapy.

The companys platform of technologies has enabled it to achieve one of the most comprehensive, late-stage clinical pipelines, addressing both the innate (activated macrophage and natural killer cell) and the adaptive immune system (dendritic, CD4 and CD8 killer T cells). In 2020, ImmunityBio is planning to enroll patients in late-stage trials with molecules across multiple indications including triple negative breast cancer, lung cancer, head and neck cancer, Merkel cell carcinoma and glioblastoma.

In the field of infectious disease, ImmunityBios goal is to develop vaccine therapies for the prevention and treatment of Influenza, Zika, Ebola, and HIV. For more information, please visit our website at https://www.immunitybio.com/.

SOURCE: NantKwest

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NantKwest and ImmunityBio Present Results of Landmark Trial of First-in-Human Natural Killer Cell Combination Immunotherapy With Durable, Complete...

Feng Li,1 Yan Chen,1,2 Shubo Liu,1 Xue Pan,1 Yulan Liu,1 Huiting Zhao,1 Xiujing Yin,1 Chunlin Yu,1 Wei Kong,1,2 Yong Zhang1,2

1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, Peoples Republic of China; 2Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, Peoples Republic of China

Correspondence: Yong ZhangSchool of Life Sciences, Jilin University, Qianjin Street No. 2699, Changchun 130012, Peoples Republic of ChinaTel +86431 85167751Fax +86431 85167674Email zhangyongking1@gmail.com

Background: Zein-based carriers are a promising delivery system for biomedical applications. However, few studies involve systematic investigation on their in vivo biocompatibility and immunogenicity.Purpose: The objective of this study was to identify the immunogenicity, type of immune response, biocompatibility and systemic recall immune response of zein nanoparticles administrated via different routes in mice.Animals and methods: Female Balb/c mice were selected as the animal model in this paper. The effect of particle size, dose and inoculation routes on immunogenicity were systematically explored. The mice were challenged at week 50 via intramuscular and subcutaneous routes to investigate the systemic recall immune responses of zein nanoparticles. Hematoxylin and eosin staining was performed to investigate the biocompatibility of zein nanoparticles at injection sites.Results: The administration of zein particles by parenteral routes led to a long-term systemic immune response. Particle size did not affect zein-specific IgG antibody titers. IgG antibody titers and inflammatory cell infiltration at the injection sites resulting from intramuscular zein particle injection were significantly higher than those from subcutaneous injection of the same dose. For intramuscular inoculation, dose-dependent IgG antibody titers were observed after the third inoculation, while no significant difference was found via the subcutaneous route. For both routes, IgG titer showed a time-dependent decrease at all dose levels from week 5 onward, and finally plateaued at week 28. The IgG subtype assay showed a predominant Th2-type immune response for both administration routes. Challenge with zein nanoparticles at week 50 led to a significant increase in specific IgG titer at all dose levels, indicating systemic recall immune responses. Interestingly, IgG antibody levels in the subcutaneous groups showed a delayed decrease compared to those of the intramuscular injection groups at all dose levels.Conclusion: This study indicated that immunogenicity may be one of the key challenges of using zein nanoparticles as carriers via parenteral administration. Further investigation is needed to illustrate zein immunogenicity in other forms, and the possible effect of systemic recall immune response on in vivo pharmacokinetic characteristics.

Keywords: zein, protein carrier, drug delivery, immune response, intramuscular injection, subcutaneous injection, parenteral administration

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The Effect of Size, Dose, and Administration Route on Zein Nanoparticl | IJN - Dove Medical Press

Todays cancer therapies are often hailed for their ability to deliver a more personalized approach one that considers the mutations lurking in a patients tumor or proteins expressed on the surface of a patients T cells and while current therapies are largely considered improvements from some past therapies, they still stand to benefit from even more personalization.

In particular, therapies can become more personalized if they address how a persons own genomics influence response to treatment, also known as pharmacogenomics, and this type of evidence is emerging for immune checkpoint inhibitors.

Specifically, a better understanding of T-cell behavior during immune checkpoint blockade is starting to form.

Its the T cells that actually do the work, Timothy Chan, MD, PhD, Memorial Sloan Kettering Cancer Center, New York City, told Cancer Therapy Advisor. He explained that because of this, its even more important that everybodys own individual genetic make-up is examined.

In a study recently published in Nature Medicine, Dr Chan and colleagues looked at the diversity of human leukocyte antigen class I (HLA-I) genes, which help the immune system fight off viruses, and juxtaposed it with the efficacy of antiCTLA-4 or antiPD-1/PD-L1 inhibitor therapy in patients with metastatic melanoma or non-small cell lung cancer. The study revealed that greater evolutionary HLA-1 diversity was linked to higher T-cell infiltration into the tumor and better response to immune checkpoint blockade.1

If youre very diverse, youre likely to benefit, Dr Chan explained. It is probably the most powerful pharmacogenomics signal that I have personally seen.

HLA diversity can vary depending on where a person lives in the world, with more isolated populations being more genetically homogenous and having lower HLA diversity, and the greater the diversity, the more efficient the immune system is at fighting off infections. However, while HLA diversity is a factor thats controlled for in vaccine clinical trials, it is not routinely examined or measured in cancer clinical trials.

I actually think that that is one of the missing pieces in understanding why some trials are positive [and] some trials are negative, Dr Chan said. Its because nobody is controlling for this one aspect that is critical for the success of immune checkpoint therapy.

In fact, the lack of consideration of HLA diversity in clinical trials may even explain the mixed success tumor mutation burden has seen as a biomarker for response to immune checkpoint inhibitors to date.2 According to Dr Chan, tumor mutation burden is only half the story and that trial investigators really need to look at the other half HLA diversity.

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Immune Checkpoint Inhibitors on Track for Better Personalization - Cancer Therapy Advisor