Publisher Health

Colin Powell, the first Black secretary of state, had multiple myeloma. The form of blood cancer hobbles the immune system and makes vaccines, including those for Covid-19, largely ineffective.It is a cancer that attacks plasma cells, which build the antibodies essential to the body’s immune defenses. It also lives in the bone marrow, crowding out the spongy material in the middle of bones and preventing healthy plasma cells from being made. In addition to weakening the immune system, the cancer can also lead to kidney damage.Multiple myeloma seems to emerge as random bad luck for those who develop the disease, and scientists cannot yet predict it based on genetic or environmental factors. But there are risk factors and Mr. Powell had them. Being Black doubles the risk, as does being male. Nearly all multiple myeloma patients are over age 45. Mr. Powell was 84.But it is a rare cancer, accounting for just 1.8 percent of cancers in the United States with 34,920 new cases a year, according to the National Cancer Institute, a rate that has remained stable for the past decade.The cancer’s five-year survival rate is 55.6 percent, which has barely declined over the past decade despite the introduction of more sophisticated drugs. About 12,410 deaths per year, or 2 percent of national cancer deaths, are the result of multiple myeloma.There’s no known way to prevent the disease.Patients in the early stages of multiple myeloma may not notice any symptoms — their disease might be detected in a routine blood or urine test. Later, when the disease is more advanced, patients may experience bone pain, fevers or frequent infections, as well as exhaustion, trouble breathing and weakness in their arms or legs. Their skin might easily bruise, and their bones might easily break.Treatments include chemotherapy and radiation and stem cell transplants, in which the cells in a person’s bone marrow are deliberately destroyed and new cells are infused to repopulate the marrow. Those replacement cells could be the patient’s own blood-forming marrow cells, removed and stored before the marrow is destroyed, or they could be cells from a closely related donor. Stem cell transplants with the patient’s own cells can put the disease into remission, but it eventually returns.The Food and Drug Administration recently approved a newer treatment designed to directly attack the cancer by harnessing the T cells of the patient’s own immune system or by using drugs designed to block particular molecules on the cancer cell surfaces.

The longer you have high levels of “bad” LDL cholesterol, the greater your risk of a heart attack.LDL, or “bad” cholesterol, is a major risk factor for coronary heart disease. Now a new study suggests that, like smoking, it has a cumulative effect over a lifetime: The longer a person has high LDL, the greater their risk of suffering a heart attack or cardiac arrest.Coronary heart disease, also known as “hardening of the arteries,” is the leading cause of death in the United States. It is caused by a buildup of plaque in the arteries that narrows the vessels and blocks the flow of oxygenated blood to the heart. Often, people have no symptoms and remain unaware they have the disease for years until they develop chest pain or suffer a catastrophic event like a heart attack.Using data from four large prospective health studies, researchers calculated LDL levels over time in 18,288 people who had multiple LDL tests taken at different ages. They calculated their cumulative exposure to LDL and followed their health for an average of 16 years. The study is in JAMA Cardiology.The researchers found that the longer a person had high levels of LDL — no matter what their LDL level is in young adulthood or middle age — the greater the risk for coronary heart disease. Compared with those in the lowest quarter for cumulative exposure, those in the highest had a 57 percent increased risk.They found no increased risk for stroke or heart failure associated with cumulative LDL exposure. The researchers suggest that many factors can contribute to heart failure, and their study had too few cases of stroke to achieve statistical significance.The study controlled for race and ethnicity, sex, year of birth, body mass index, smoking, high-density lipoprotein (HDL, or “good” cholesterol), blood pressure, Type 2 diabetes and the use of lipid-lowering and blood pressure medicines.In people under 40, current guidelines recommend treatment with cholesterol-lowering statin drugs only with LDL readings higher than 190, but the researchers found that the increased risk for coronary heart disease may start at a much lower level. (LDL levels below 100 are generally considered normal.)“Our figures suggest that the risk starts at LDL levels as low as 100,” said the lead author, YiYi Zhang, an assistant professor of medical sciences at Columbia. “That doesn’t necessarily mean that a person under 40 with an LDL of 100 should immediately start treatment. We need more evidence to determine the optimal combination of age and LDL level.”Dr. Tamara Horwich, a cardiologist and professor of medicine at the University of California, Los Angeles, who was not involved in the study, noted that medical guidelines on choosing who needs statin therapy are heavily weighted toward older people, since advancing age is a major risk factor for complications from heart disease.Still, she said, “From autopsy studies, we have known for some time that atherosclerosis begins to develop in the arteries of young individuals, as early as the teens and 20s. I think this study may entice physicians to move the needle back on the age of starting, or at least thinking about starting, statin therapy.”Young people have a low short-term risk, Dr. Zhang said, but a high long-term risk. “The main message is to try to maintain low LDL through middle age. That will reduce your heart disease risk.”

A Northwestern Medicine study in mice has identified new treatment targets for glaucoma, including preventing a severe pediatric form of glaucoma, as well as uncovering a possible new class of therapy for the most common form of glaucoma in adults.
In people with high pressure glaucoma, fluid in the eye doesn’t properly drain and builds up pressure on the optic nerve, leading to vision loss. It affects 60 million people worldwide and is the most common cause of blindness in people over 60 years old.
While there are a few treatments available for open angle glaucoma, the most common form of glaucoma in adults (eye drops, oral medication, laser treatments), there are no cures, and a severe form of glaucoma in children between birth and three years old known as primary congenital glaucoma can only be treated with surgery.
“Although primary congenital glaucoma is much rarer than open angle glaucoma, it is devastating for children,” said corresponding author Dr. Susan Quaggin, chief of nephrology and hypertension in the Department of Medicine at Northwestern University Feinberg School of Medicine. “New treatments and new classes of treatments are urgently needed to slow vision loss in both forms.
Using gene editing, the scientists in the study developed new models of glaucoma in mice that resembled primary congenital glaucoma. By injecting a new, long-lasting and non-toxic protein treatment (Hepta-ANGPT1) into mice, the scientists were able to replace the function of genes that, when mutated, cause glaucoma. With this injectable treatment, the scientists also successfully prevented glaucoma from ever forming in one model. This same therapy, when injected into the eyes of healthy adult mice, reduced pressure in the eyes, supporting it as a possible new class of therapy for the most common cause of glaucoma in adults (high intraocular pressure open angle glaucoma).
The study, “Cellular crosstalk regulates the aqueous humor outflow pathway and provides new targets for glaucoma therapies,”was published today, Oct. 18, in the journal Nature Communications.
The next step is to develop the appropriate delivery system for the successful new protein treatment in patients and bring it to production, Quaggin said.
Additionally, the scientists used bioinformatics and single cell RNA sequence data to understand and identify glaucoma pathways that can be explored in the future for additional therapeutic targets for the disease, such as ones that regulate communication with a specialized blood vessel in the eye (Schlemm’s canal) that is important for draining fluid and maintaining normal eye pressure.
“Having a treatment that can promote remodeling and/or growth of a defective Schlemm’s canal to treat glaucoma would be fantastic,” Quaggin said. “These studies are the first step to that goal.
“Our hope is that this study leads to the first targeted therapy that effectively promotes (aqueous humor) fluid outflow from the front of an eye, reversing the underlying biologic defect in patients with glaucoma.”
Other Northwestern co-authors are Ben Thompson (first), Dr. Jing Jin, Pan Liu and medical student Raj Purohit. This study builds on major teamwork and an ongoing collaboration with University of Madison-Wisconsin co-authors Terri Young and Stuart Thomson.
Story Source:
Materials provided by Northwestern University. Original written by Kristin Samuelson. Note: Content may be edited for style and length.

Lateral flow assays — LFAs, often called ‘dipsticks’ — have been a standard point-of-care testing platform for decades, and keep growing in popularity, especially in developing countries. These disposable, paper-based diagnostic devices are affordable, widely available, have a long shelf life, and they’re fast, typically delivering test results in less than 20 minutes.
They’re also easy to use at home. The user adds a few drops of a sample — saliva, blood, or urine, for instance — to one end of the dipstick, and within minutes reads the results at the other end.
The technology has been widely used to determine the presence or absence of biomarkers in humans, as well as contaminants in water or food. Most commonly, LFA technology is used for at-home pregnancy tests. And more recently, LFA technology has been used successfully in at-home tests for Covid-19.
“These tests have been extremely popular for years, mainly because they are so simple to use. You don’t send anything to the lab or clinic because these tests don’t require any external equipment to operate. This is an advantage,” said engineering researcher Fatih Sarioglu, who runs the Biomedical Microsystems Laboratory at the Georgia Institute of Technology. “But there also is a disadvantage. There are limitations to what they can do.”
Recognizing the widespread popularity and practicality of dipsticks, particularly in resource-limited settings, Sarioglu and his research team are overcoming those limitations with development of a flow control technology, turning these simple tests into complex biomedical assays.
They explain their research, and its emphasis on flow technology, in two recently published papers in the journals Science Advances and ACS Sensors. One explains the development of their technology and the other applies the technology in a toolkit to diagnose the novel coronavirus, as well as influenza.

Nearly half of our DNA has been written off as junk, the discards of evolution: sidelined or broken genes, viruses that got stuck in our genome and were dismembered or silenced, none of it relevant to the human organism or human evolution.
But research over the last decade has shown that some of this genetic “dark matter” does have a function, primarily in regulating the expression of host genes — a mere 2% of our total genome — that code for proteins. Biologists continue to debate, however, whether these regulatory sequences of DNA play essential or detrimental roles in the body or are merely incidental, an accident that the organism can live without.
A new study led by researchers at University of California, Berkeley, and Washington University explored the function of one component of this junk DNA, transposons, which are selfish DNA sequences able to invade their host genome. The study shows that at least one family of transposons — ancient viruses that have invaded our genome by the millions — plays a critical role in viability in the mouse, and perhaps in all mammals. When the researchers knocked out a specific transposon in mice, half their mouse pups died before birth.
This is the first example of a piece of “junk DNA” being critical to survival in mammals.
In mice, this transposon regulates the proliferation of cells in the early fertilized embryo and the timing of implantation in the mother’s uterus. The researchers looked in seven other mammalian species, including humans, and also found virus-derived regulatory elements linked to cell proliferation and timing of embryo implantation, suggesting that ancient viral DNA has been domesticated independently to play a crucial role in early embryonic development in all mammals.
According to senior author Lin He, UC Berkeley professor of molecular and cell biology, the findings highlight an oft-ignored driver of evolution: viruses that integrate into our genome and get repurposed as regulators of host genes, opening up evolutionary options not available before.

Nestled deep in the middle of the vertebrate brain is a multi-sensory integration and movement control center called the superior colliculus. In rodents, this brain region integrates multi-sensory inputs — visual cues, sounds, touch information, and smells — and delivers output signals to a variety of motor control centers in the brain, coordinating the animal’s movements in response to its environment.
Although the superior colliculus composes a relatively small portion of the brain’s volume in mice, it’s a processing powerhouse — in part, because it’s formed by precise cellular layers that organize and refine signaling patterns.
Now, a team of researchers led by Michael Fox, professor at the Fralin Biomedical Research Institute at VTC, have uncovered a key link in how this processing hub’s layers develop to decode visual cues from the eye and regulate key survival instincts in mice. The study was published in the Proceedings of the National Academy of Science.
“This brain region is interesting because it integrates data from multiple sensory inputs, helps form a binocular image of the world, and then dictates the animal’s innate behaviors — such as running away from a predator or hunting prey — based on those data,” said Fox, who is also the director of the Virginia Tech College of Science’s School of Neuroscience.
During early brain development — weeks before a mouse opens its eyes for the first time -neurons extend long axonal processes from back of the eye, forming the optic nerve. These growing cells eventually branch off to shape thousands of intricate connections in precise brain regions, including the superior colliculus.
How these cells know where to migrate largely remains a mystery, Fox says. But understanding this key phase of development could potentially provide new information that could help researchers in future studies identify ways to regenerate injured optic nerve fibers.

Oxygen-deprived newborns who undergo cooling therapy to protect their brains are at an elevated risk of seizures and brain damage during the rewarming period, which could be a precursor of disability or death, a new study by a team of researchers led by a UT Southwestern pediatrician suggests. The finding, published online in JAMA Neurology, could lead to better ways to protect these vulnerable patients during an often overlooked yet critical period of cooling — or hypothermia — therapy.
“A wealth of evidence has shown that cooling babies who don’t receive enough oxygen during birth can improve their neurodevelopmental outcomes, but few studies have looked at events that occur as they are rewarmed to a normal body temperature,” said study leader Lina Chalak, M.D., MSCS, Professor of Pediatrics and Psychiatry at UT Southwestern, and Associate Division Chief of Neonatology and founding Medical Director of the Neonatal Neurology Program at Parkland Hospital. “We’re showing that there’s a significantly elevated risk of seizures during the rewarming period, which typically go unnoticed and can cause long-term harm.”
Millions of newborns worldwide are affected by neonatal hypoxic-ischemic encephalopathy (HIE), brain damage initially caused by a lack of oxygen during birth. Although the World Health Organization estimates that birth asphyxia is responsible for nearly a quarter of all neonatal deaths, those babies that survive oxygen deprivation are often left with neurological injuries, Dr. Chalak explained.
To help improve outcomes, babies diagnosed with HIE are treated with hypothermia, using a cooling blanket that brings the body temperature down to as low as 33.5°C, said Dr. Chalak — a treatment implemented 15 years ago by the National Institutes of Health’s (NIH) Neonatal Research Network, of which UT Southwestern has long been a member.
Initial studies showed that during cooling, babies with HIE commonly have symptomless seizures — neurological events that can further damage the brain — prompting electroencephalographic (EEG) monitoring to become a standard part of the hypothermia protocol. However, Dr. Chalak explained, babies typically haven’t been monitored during the rewarming period, in which the temperature of the blanket is increased by 0.5°C every hour until babies reach a normal body temperature.
To better understand seizure risk during rewarming, Dr. Chalak and colleagues from 21 different institutions in the Neonatal Research Network studied 120 babies who were enrolled in another study that compared two different cooling protocols, one longer and colder than the other. In Dallas, patients were enrolled at Parkland Health & Hospital System, with follow-ups at Children’s Health. As part of the new study, the babies were also monitored with EEG to check for seizures both during the cooling and the rewarming phases of hypothermia.
When the researchers compared data from the last 12 hours of cooling and the first 12 hours of rewarming, they found that rewarming increased the odds of seizures about three-fold. In addition, babies who had seizures during rewarming were about twice as likely to die or have a neurological disability by age 2, compared with those who didn’t have seizures during this period. This finding held true even after adjusting for differences in medical centers and the newborns’ HIE severity.
Although it’s not known how to prevent seizures from occurring in babies with HIE, treating seizures when they do occur can help prevent further brain damage, Dr. Chalak said. Consequently, monitoring during both cooling and rewarming can help protect these young patients’ brains from further insults while they heal.
“This study is telling us that there’s an untapped opportunity to improve care for these babies during rewarming by making monitoring a standard part of the protocol,” Dr. Chalak said.
Story Source:
Materials provided by UT Southwestern Medical Center. Note: Content may be edited for style and length.

Michael Regan, the E.P.A. administrator, wants to limit a class of chemicals that has been linked to cancer and is found in everything from drinking water to furniture.WASHINGTON — The Biden administration on Monday said it would require chemical manufacturers to test and publicly report the amount of a family of chemicals known as PFAS that is contained in household items like tape, nonstick pans and stain-resistant furniture, the first step toward reducing their presence in drinking water.Perfluoroalkyl and polyfluoroalkyl compounds, or PFAS refers to more than 4,000 man-made chemicals that are often called “forever chemicals” because they don’t break down in the environment. Exposure to the chemicals has been linked to certain cancers, weakened immunity, thyroid disease, and other health effects.Michael S. Regan, the administrator of the Environmental Protection Agency, said in an interview that regulating PFAS has been one of his priorities. He previously served as the top environmental regulator in North Carolina where startlingly high concentrations of the chemicals were found in several sources of public drinking water.“PFAS contamination has been devastating communities for decades. I saw this first hand in North Carolina,” Mr. Regan said. He recounted visiting with mothers unsure if their children’s drinking water was safe, and caregivers wondering if a loved one’s terminal illness was associated with exposure to the chemicals.The new E.P.A. testing requirements will go into effect “in a matter of weeks,” Mr. Regan said. The agency did not provide an estimate of the cost to manufacturers but Mr. Regan said it is a cost that industry, not taxpayers, should bear.“It could be expensive, but it’s necessary,” Mr. Regan said. “It’s time for manufacturers to be transparent and provide the American people with this level of detail,” he said.Thousands of chemicals classified as PFAS are ubiquitous in consumer products because they increase resistance to heat, stains, water and grease. The E.P.A. plans to group the chemicals into 20 subcategories based on shared characteristics. By the end of 2021, the E.P.A. will require manufacturers to test chemicals from each grouping, which the agency said will yield data on more than 2,000 PFAS to inform E.P.A. plans going forward.Mr. Regan will announce the new policies at North Carolina State University in Raleigh flanked by local officials including Democratic Gov. Roy Cooper.The E.P.A. announced additional regulatory steps it intends to formally propose by 2022 that involve PFAS, Mr. Regan said.The list, which the E.P.A. described as a “road map” includes setting legal limits for safe levels of PFAS in drinking water, which the chemical industry tentatively supports; designating it as a hazardous substance under the laws that govern toxic Superfund sites, which industry opposes; and increasing monitoring and research.Meanwhile the Department of Defense, is expected to review how to clean PFAS contamination at nearly 700 military installations and National Guard locations by the end of 2023. The chemicals are in a foam used at military installations and by civilian firefighters to extinguish fires.The E.P.A. has set a lifetime health advisory for two types of PFAS in drinking water at 70 parts per trillion — essentially cautioning that sustained exposure above that level could cause adverse effects. Agency officials said it is too soon to say whether the E.P.A. will recommend that threshold or a different one when it develops formal drinking water limits.The American Chemistry Council, a trade organization, noted that about 600 chemicals in the PFAS category are used to manufacture products like solar panels and cellphones, and said alternative materials might not be available to replace them. “The American Chemistry Council supports the strong, science-based regulation of chemicals, including PFAS substances. But all PFAS are not the same, and they should not all be regulated the same way,” Erich Shea, a spokesman for the organization, said in a statement.Environmentalists said they don’t believe there is a safe level of PFAS in drinking water.Kemp Burdette, 47, works for Cape Fear River Watch in Wilmington, N.C., where he used to encourage people to drink tap water to avoid using disposable plastic bottles. Then he discovered that PFAS levels in the local tap water had reached as high as 6,000 parts per trillion, the result of years of contaminated wastewater discharged into the Cape Fear River by a Dupont plant, later owned by The Chemours Company.“All of a sudden you’re like, ‘What’s in the water? What is this stuff? How long have we been drinking it’?” Mr. Burdette said. “My kids were drinking that water all their lives.”The North Carolina Department of Environmental Quality, then under the leadership Mr. Regan, ultimately reached an agreement requiring Chemours to pay a $13 million fine.A spokesman for Chemours referred questions to the American Chemistry Council.President Biden has called for about $10 billion in funding to address PFAS contamination through a bipartisan infrastructure package and a separate budget bill that Congress has been struggling to approve.

Over the last few decades, scientists have discovered that long-term calorie restriction provides a wealth of benefits in animals: lower weight, better blood sugar control, even longer lifespans.
Researchers have largely assumed that reduced food intake drove these benefits by reprogramming metabolism. But a new study from University of Wisconsin-Madison researchers finds that reduced calorie intake alone is not enough; fasting is essential for mice to derive full benefit.
The new findings lend support to preliminary evidence that fasting can boost health in people, as trends like intermittent fasting continue to hold sway. These human and animal studies have added to the growing picture of how health is controlled by when and what we eat, not just how much.
The research further emphasizes the complexity of nutrition and metabolism and provides guidance to researchers trying to untangle the true causes of diet-induced health benefits in animals and humans.
The researchers discovered that, combined with eating less, fasting reduces frailty in old age and extends the lifespan of mice. And fasting alone can improve blood sugar and liver metabolism.
Surprisingly, mice that ate fewer calories but never fasted died younger than mice that ate as much as they wanted, suggesting that calorie restriction alone may be harmful.

Circadian clocks, which regulate most of the physiological processes of living beings over a rhythm of about 24 hours, are one of the most fundamental biological mechanisms. By deciphering the cell migration mechanisms underlying the immune response, scientists from the University of Geneva (UNIGE), in Switzerland, and the Ludwigs-Maximilians University (LMU), in Germany, have shown that the activation of the immune system is modulated according to the time of day. Indeed, the migration of immune cells from the skin to the lymph nodes oscillates over a 24-hours period. Immune function is highest in the resting phase, just before activity resumes — in the afternoon for mice, which are nocturnal animals, and early morning for humans. These results, which can be read in the journal Nature Immunology, suggest that the time of day should possibly be taken into account when administering vaccines or immunotherapies against cancer, in order to increase their effectiveness.
Unlike the innate immune system, which reacts immediately but in a non-targeted way, the adaptive immune system builds a long-term response specific to each infectious agent.”The adaptive immune system takes weeks to form a response specific to a given pathogen. This response then lasts for a long time thanks to a cellular memory mechanism,” says Christoph Scheiermann, a professor in the Department of Pathology and Immunology and in the Geneva Centre for Inflammation Research (GCIR) at UNIGE Faculty of Medicine, who led this research. “This is typically the mechanism at work during vaccination against a virus, for example.”
To understand the role of circadian rhythms on immune activation, the researchers looked at the migration of dendritic cells from the skin into the lymphatic system, one of the pillars of the adaptive immune response. Located in many peripheral organs, including the skin, dendritic cells migrate through the lymphatic vessels to the lymph nodes, where antigens are presented, in order to trigger an immune response against an incoming pathogen.
Synchronised clocks
The scientists first observed the migratory capacity of dendritic cells in wild mice four times a day, then in mice without functional internal clocks. “For cell migration to take place correctly, not only the dendritic cells but also the lymphatic vessel cells must respond to a circadian rhythm,” explains Stephan Holtkamp, then a researcher at the Biomedical Center of the Ludwig-Maximilian University and first author of this study. The circadian clock must therefore be functional on both sides of the mechanism: in the cell and in its environment. If not, the activity peaks no longer occur and the immune system continuously works in slow motion.
The researchers then repeated their experiment on human skin cells taken from patients at different times of the day. “We identified numerous molecules, in particular chemokines, which are involved in the migratory process and whose expression is regulated by circadian clocks,” says Christoph Scheiermann. “The same molecules were found in human and mouse cells with an inverted rhythm corresponding to the life habits of the two species, nocturnal for rodents, diurnal for humans. This confirms that this rhythm is governed by natural activity according to the alternation of day and night.”
Stimulating the immune system at a favourable time
Additional data also indicate that if the immune system is stimulated at different times of the day, the same oscillations appear, with a peak in the morning. But why is the immune system governed by an oscillatory rhythm? “Circadian rhythms function as an energy-saving system to make the best use of energy resources according to the most immediate needs. Could this be a way for the immune system to be on alert at times when the risk of exposure to pathogens is greatest, through the ingestion of food and/or social interactions?” Likewise, could we be more vulnerable to pathogens in the evening and at night? It is impossible to say for the moment. Nevertheless, the importance of the circadian rhythm on the immune system is only just being to be revealed and could be of major importance both for preventive vaccination and for the administration of anti-tumour therapies or the management of autoimmune diseases. Christoph Scheiermann’s team will now explore in more detail the very first stage of the immune response, when the pathogen or vaccine enters the body.
Story Source:
Materials provided by Université de Genève. Note: Content may be edited for style and length.