Single-cell CRISPR technology deciphers role of chromatin accessibility in cancer

In a new resource for the scientific community, published today in Nature Biotechnology, researchers in the lab of Neville Sanjana, PhD, at the New York Genome Center (NYGC) and New York University (NYU) developed CRISPR-sciATAC, a novel integrative genetic screening platform that jointly captures CRISPR gene perturbations and single-cell chromatin accessibility genome-wide. With this technology, they profile changes in genome organization and create a large-scale atlas of how loss of individual chromatin-altering enzymes impacts the human genome. The new method harnesses the programmability of the gene editing system CRISPR to knock-out nearly all chromatin-related genes in parallel, offering researchers deeper insights into the role of DNA accessibility in cancer and in rare diseases involving chromatin.
Recent advances in single-cell technologies have given scientists the ability to profile chromatin, the complex of DNA and proteins that resides within the nucleus of individual cells. Chromatin is often called the “gatekeeper” of the genome because its proteins act as packaging elements for the DNA, either promoting or refusing access to it. This controls gene expression processes in the cell, such as turning on or off specific genes. Changes in the chromatin landscape have been linked to diverse human traits and diseases, most notably cancer.
In an initial demonstration of CRISPR-sciATAC, the Sanjana Lab team designed a CRISPR library to target 20 chromatin-modifying genes that are commonly mutated in different cancers, including breast, colon, lung and brain cancers. Many of these enzymes act as tumor suppressors and their loss results in global changes in chromatin accessibility. For example, the group showed that loss of the gene EZH2, which encodes a histone methytransferase, resulted in an increase in gene expression across several previously silenced developmental genes.
“The scale of CRISPR-sciATAC makes this dataset very unique. Here, in a uniform genetic background, we have accessibility data capturing the impact of every chromatin-related gene. This provides a detailed map between each gene and how its loss impacts genome organization with single-cell resolution,” said Dr. Noa Liscovitch-Brauer, a postdoctoral fellow in Sanjana’s lab at the New York Genome Center and NYU and the study’s co-first author.
In total, the team targeted more than 100 chromatin-related genes and developed a “chromatin atlas” that charts how the genome changes in response to loss of these proteins. The atlas shows that different subunits within each of the 17 chromatin remodeling complexes targeted can have different effects on genome accessibility. Surprisingly, nearly all of these complexes have subunits where loss triggers increased accessibility and other subunits with the opposite effect. Overall, the greatest disruption in transcription factor binding sites, which are important functional elements in the genome, was observed after loss of AT-rich interactive domain-containing protein 1A (ARID1A), a member of the BAF complex. Mutations in BAF complex proteins are estimated to be involved in 1 out of every 5 cancers.
In addition to the CRISPR-sciATAC method, the team also developed a suite of computational methods to map the dynamic movements of the nucleosomes, which are the protein clusters that DNA is wrapped around. When there are more nucleosomes, the DNA is tightly wound and less available to bind transcription factors. This is exactly what the team found at specifical transcription factor binding sites involved in cell proliferation after CRISPR knock-out of ARID1A. When targeting a different chromatin-modifying enzyme, these same sites underwent an expansion in nucleosome spacing, demonstrating the dynamics of nucleosome positioning at specific sites in the genome. The CRISPR-sciATAC method allowed the team to systematically explore this genome plasticity for multiple chromatin-modifying enzymes and transcription factor binding sites.
“We really focused on making CRISPR-sciATAC an accessible technique — we wanted it to be something that any lab could do. We produced most of the key enzymes in-house and used simple methods for single-cell isolation that do not require microfluidics or single-cell kits,” said Dr. Antonino Montalbano, a former postdoctoral fellow in Sanjana’s lab at the New York Genome Center and NYU and the study’s co-first author.
To develop the CRISPR-sciATAC technology, the researchers used a mix of human and mouse cells to create a tagging/identification process that allowed them to split and barcode the nuclei of cells as well as capture the single-guide RNAs required for CRISPR targeting. The work builds off prior single-cell combinatorial indexing ATAC-seq (sciATAC-seq) work from Dr. Jay Shendure at the University of Washington and other groups developing new single-cell genomics methods. CRISPR-sciATAC also uses an unique, easy-to purify transposase that was developed in the NYGC’s Innovation Technology Lab. A key technical hurdle was optimizing experimental conditions to simultaneously capture the CRISPR guide RNAs and genome fragments for accessibility profiling while also keeping the nuclear envelope of each cell intact.
“Integrating chromatin accessibility profiling into the genome-wide CRISPR screens provides a new lens for us to understand gene regulation,” said Dr. Sanjana, Core Faculty Member, NYGC, Assistant Professor of Biology, NYU, and Assistant Professor of Neuroscience and Physiology, NYU Grossman School of Medicine, the study’s senior author. “With CRISPR-sciATAC, we have a comprehensive view into how specific chromatin-modifying enzymes and complexes change accessibility and orchestrate the interactions that control gene expression. Chromatin sets the stage for gene expression, and here we can measure the impact of different mutations on chromatin rapidly. We hope this atlas will be a broadly useful resource for the community and that CRISPR-sciATAC will be used to produce similar atlases in other biological systems and disease contexts.”
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Fasting lowers blood pressure by reshaping the gut microbiota

Nearly half of adults in the United States have hypertension, a condition that raises the risk for heart disease and stroke, which are leading causes of death in the U. S.
At Baylor College of Medicine, Dr. David J. Durgan and his colleagues are dedicated to better understand hypertension, in particular the emerging evidence suggesting that disruption of the gut microbiota, known as gut dysbiosis, can have adverse effects on blood pressure.
“Previous studies from our lab have shown that the composition of the gut microbiota in animal models of hypertension, such as the SHRSP (spontaneously hypertensive stroke-prone rat) model, is different from that in animals with normal blood pressure,” said Durgan, assistant professor of anesthesiology at Baylor.
The researchers also have shown that transplanting dysbiotic gut microbiota from a hypertensive animal into a normotensive (having a healthy blood pressure) one results in the recipient developing high blood pressure.
“This result told us that gut dysbiosis is not just a consequence of hypertension, but is actually involved in causing it,” Durgan said. “This ground work led to the current study in which we proposed to answer two questions. First, can we manipulate the dysbiotic microbiota to either prevent or relieve hypertension? Second, how are the gut microbes influencing the animal’s blood pressure?”
Can manipulating the gut microbiota regulate blood pressure?
To answer the first question, Durgan and his colleagues drew on previous research showing that fasting was both one of the major drivers of the composition of the gut microbiota and a promoter of beneficial cardiovascular effects. These studies, however, had not provided evidence connecting the microbiota and blood pressure.

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With New C.D.C Mask Rules, Uncertainty on How to Proceed

After the C.D.C. issued new guidelines, people are figuring out how to proceed. Some want to keep their face coverings on: “It saves me having to put on sunscreen.”Mark Rasch hopped on his bike Tuesday in Bethesda, Md., pedaled off for an afternoon ride, and realized he forgot his mask. As he turned back for it, news came on the radio over his earbuds: The Centers for Disease Control and Prevention said masks were no longer required outdoors for fully vaccinated people unless they were in a crowd.Mr. Rasch, a lawyer, rode on, naked from nose to chin for the first time in a year. He reached nearby Georgetown and found he was nearly alone in that almost everyone else there remained masked.“I wondered if there was a store I could go into without wearing a mask to buy a mask?” he said. Instead, he went home, and told his wife: “Nothing is changing, but it’s happening quickly.”It’s springtime of the pandemic. After the trauma of the last year, the quarantined are emerging into sunlight, and beginning to navigate travel, classrooms and restaurants. And they are discovering that when it comes to returning to the old ways, many feel out of sorts. Do they shake hands? Hug? With or without a mask?It’s a confusion exacerbated by changing rules, state and federal, that vary by congressional district or even neighborhood, all while the very real threat of infection remains, in some places more than others.Many states and cities are scrambling to incorporate the agency’s new counsel into their own rules. New York has ended its curfew. In California, where masks remain recommended, the authorities are looking to reconcile the clash of cues.“We have reviewed and support the C.D.C.’s new masking recommendations and are working quickly to align California’s guidance with these common sense guidelines,” Dr. Tomás Aragón, the director of the California Department of Public Health, said in a statement.Visitors to the Lincoln Memorial in Washington on Tuesday, the day the C.D.C. updated its outdoor mask guidance.Erin Schaff/The New York TimesDr. Susan Huang, of the University of California, Irvine, Medical School, explained the conflicted psychology as a function of rapidly changing risk, and the difference in tolerance individuals have for risk. At present, she said, most places have a foundation of people vaccinated but are not near the 80 percent that marks herd immunity — with no children inoculated.“We’re between the darkness and the light,” Dr. Huang said. She likened the psychology around masks and other behavior to the different approaches people take to changing their wardrobes at the end of winter: People who are more risk averse continue to wear winter clothes on 50 degree days, where bigger risk takers opt for shorts.“Eventually,” she said, “everyone will be wearing shorts.”It seems that this psychology may come to define the way the pandemic ebbs, revolving less around public dictate than personal comfort after a stark trauma. For many, the jurisdictional battle is internal, with head and heart clashing over the right personal policy.“I have hugged friends but in a very clumsy body posture,” said Shirley Lin, who lives in Fremont, Calif., where she works on business development at a mobile game company. “The bear hugs with the joyful scream will not be seen for a long, long time.”Her partner lost his mother to Covid-19. She died in August in St. Petersburg, Russia, at age 68. Ms. Lin, scarred, is dubious that the risk has passed. “I don’t think we can slack off on the proper social distancing and masking,” she said. But “we are much more optimistic.”Masks have also become so much more than mere barrier between germs and lungs. They can keep that too-chatty neighbor at bay or help the introvert hide in plain sight. And vanity? Goodbye to that.“It saves me having to put on sunscreen and wear lipstick,” said Sara J. Becker, an associate professor at the Brown University School of Public Health.Children in Fort Greene Park in Brooklyn on Tuesday. The U.S. is still a ways away from reaching herd immunity, and children have yet to be inoculated.Stephanie Keith for The New York TimesShe recently had an awkward transitional moment when she, her husband and two children went to an outdoor fire pit with vaccinated neighbors.“Someone offered me their hand, and I gave my elbow,” Ms. Becker said. She was “not quite ready for handshakes or hugs,” she explained, though “pre-Covid, I was definitely a hugger.”So was Dr. Shervin Assari, but he’s abstaining — at least for now, particularly after the last few weeks. His mother, who lives in Tehran, was just released from the hospital there after a dangerous bout with Covid-19, and Dr. Assari feels chastened anew.“I had an abstract idea about the risk, and now I really see the risk,” said Dr. Assari, who lives in Lakewood, Calif. He’s “half-vaccinated,” he said, “and terribly scared of Covid-19.”Dr. Assari, a public health expert, is trying to modulate his own behavior given the three different worlds he’s trying to navigate: in the working-class neighborhood where he lives in South Los Angeles; his daughter’s elementary school; and the historically Black medical school, Charles Drew University of Medicine and Science, where he teaches family medicine.Each differs in culture. Most residents of his neighborhood wear masks, but also seem to him respectful of individual choice. The elementary school maintains rigid standards with daily checklists to make sure no one is sick or at risk.And at the medical school, people religiously wear masks, even as the school roils with mistrust of the vaccination, despite the fact it trains doctors, nurses and others in the field.An unmasked cyclist in Charlotte on Tuesday.Travis Dove for The New York Times“It’s shocking — it’s very deep mistrust, not just moderate,” Dr. Assari said. The skepticism of the medical establishment was centuries in the making, and he doubts it will end soon. But, he said, the mistrust in the Black community is different from that of conservatives: Vaccination may be slow among both groups, but white conservatives may be quicker to rip off their masks, if they wore them at all.“There’s none of that Tucker Carlson stuff here,” he said. Mr. Carlson, a talk-show host on Fox News, said on a recent show that having children wear a mask outside should “be illegal” and that “your response should be no different than seeing someone beat a kid at Walmart” and to call the police.(Dr. Anthony Fauci, the president’s chief medical adviser for Covid, promptly shot back on CNN: “I think that’s self-evident that that’s bizarre.”)In San Francisco, Huntley Barad, a retired entrepreneur, ventured out with his wife this week, and they took their first walk without masks in more than a year.“We walked down the Great Highway,” he said. “We’re ready to poke our heads out from underneath our rock, and perhaps find a restaurant with a nice outdoor table setup — on a warmish night if possible.”But he said that their plans for a date night weren’t firm, much like the conflicting guidance and behavior of a nation itself.“Nothing definite yet.”

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Low risk of infection in babies born to mothers with COVID-19, study finds

Researchers at Karolinska Institutet and the Public Health Agency of Sweden have studied newborn babies whose mothers tested positive for SARS-CoV-2 during pregnancy or childbirth. The results show that although babies born of test-positive mothers are more likely to be born early, extremely few were infected with COVID-19. The study, published in JAMA, supports the Swedish recommendation not to separate mother and baby after delivery.
The population-based study comprised 92 per cent of all neonates — almost 90,000 births — in Sweden during the first year of the pandemic (11 March 2020 to 31 January 2021), making it one of the largest datasets in the field to date.
The results show a slightly higher level of morbidity in neonates whose mothers tested positive for SARS-CoV-2, including an increased risk of respiratory disorders, which were largely due to the higher number of preterm births in this group. No direct correlation between maternal infection and neonatal respiratory infection or pneumonia could be observed.
A total of 2,323 babies were born to SARS-CoV-2-positive mothers, of whom about one third were tested close to or just after childbirth. Only 21 (0.9 per cent) of the babies of these women tested positive for the virus at some point during the newborn period (the first 28 days), the majority without displaying any symptoms; a few babies were treated for other reasons than COVID-19.
The study supports the Swedish recommendation that babies born of women who have tested positive for SARS-CoV-2 while pregnant or during delivery do not need to be routinely separated from their mothers at birth. In many countries such a precautionary measure is taken despite the lack of supporting evidence.
“Separating a newborn baby from its mother is a serious intervention with negative consequences for the health of both mother and baby that must be weighed against the possible benefits,” says Mikael Norman, professor of paediatrics at the Department of Clinical Science, Intervention and Technology, Karolinska Institutet, and one of the researchers leading the study. “Our study suggests that mother and baby can be cared for together and that nursing can be recommended without danger to the baby’s health. This is good news for all pregnant women, their babies and postnatal and neonatal staff.”
The study was made possible through daily reports to three Swedish registries: the National Quality Register for Pregnancy, the National Quality Register for Neonatal Care, and the Communicable Diseases Register (SmiNet). SmiNet is a system for reporting communicable diseases used jointly by the Public Health Agency of Sweden and the regional communicable diseases units to surveille the 60-plus notifiable diseases that must be reported in accordance with the Communicable Diseases Act.
“By cross-referencing the three registries we’ve been able to monitor and report outcomes for the neonates in real time during both the first and second waves of COVID-19,” says Professor Norman.
The study was financed by the Swedish Society of Medicine, NordForsk, Region Stockholm (ALF funding) and the Childhood Foundation of the Swedish Order of Freemasons in Stockholm. Co-author Jonas F. Ludvigsson leads a study on behalf of the Swedish IBD quality register (SWIBREG), which has received funding from Janssen. No other potential conflicts of interest have been reported.
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Baby's first stool can help predict risk of developing allergies

It may seem like an unusual place to go looking for answers, but the contents of a baby’s first diaper can reveal a lot about a newborn’s future health.
In a new study published today in Cell Reports Medicine, a team of University of British Columbia (UBC) researchers has shown that the composition of a baby’s first poop — a thick, dark green substance known as meconium — is associated with whether or not a child will develop allergies within their first year of life.
“Our analysis revealed that newborns who developed allergic sensitization by one year of age had significantly less ‘rich’ meconium at birth, compared to those who didn’t develop allergic sensitization,” says the study’s senior co-author Dr. Brett Finlay, a professor at the Michael Smith Laboratories and departments of biochemistry and molecular biology, and microbiology and immunology at UBC.
Meconium, which is typically passed within the first day of life, is made up of a variety of materials ingested and excreted during development, ranging from skin cells, amniotic fluid and various molecules known as metabolites.
“Meconium is like a time capsule, revealing what the infant was exposed to before it was born. It contains all sorts of molecules encountered and accumulated from the mother while in the womb, and it then becomes the initial food source for the earliest gut microbes,” says the study’s lead author Dr. Charisse Petersen, a research associate in UBC’s department of pediatrics.
As part of the study, the researchers analyzed meconium samples from 100 infants enrolled in the CHILD Cohort Study (CHILD), a world-leading birth cohort study in maternal, newborn and child health research.
They discovered that the fewer different types of molecules a baby’s meconium contained, the greater the child’s risk of developing allergies by one year. They also found that a reduction in certain molecules was associated with changes to key bacterial groups. These bacteria groups play a critical role in the development and maturation of a vast ecosystem of gut microbes, known as the microbiota, which is a powerful player in health and disease.
“This work shows that the development of a healthy immune system and microbiota may actually start well before a child is born — and signals that the tiny molecules an infant is exposed to in the womb play a fundamental role in future health,” says Dr. Petersen.
Using a machine-learning algorithm, the researchers combined meconium, microbe and clinical data to predict with a high degree of accuracy (76 per cent), and more reliably than ever before, whether or not an infant would develop allergies by one year of age.
The study findings have important implications for at-risk infants, say the researchers.
“We know that children with allergies are at the highest risk of also developing asthma. Now we have an opportunity to identify at-risk infants who could benefit from early interventions before they even begin to show signs and symptoms of allergies or asthma later in life,” says the study’s senior co-author Dr. Stuart Turvey, a professor in UBC’s department of pediatrics, investigator at BC Children’s Hospital and co-director of the CHILD Cohort Study.
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New cell atlas of COVID lungs reveals why SARS-CoV-2 is deadly and different

A new study is drawing the most detailed picture yet of SARS-CoV-2 infection in the lung, revealing mechanisms that result in lethal COVID-19, and may explain long-term complications and show how COVID-19 differs from other infectious diseases.
Led by researchers at Columbia University Vagelos College of Physicians and Surgeons and Herbert Irving Comprehensive Cancer Center, the study found that in patients who died of the infection, COVID-19 unleashed a detrimental trifecta of runaway inflammation, direct destruction and impaired regeneration of lung cells involved in gas exchange, and accelerated lung scarring.
Though the study looked at lungs from patients who had died of the disease, it provides solid leads as to why survivors of severe COVID may experience long-term respiratory complications due to lung scarring.
“It’s a devastating disease, but the picture we’re getting of the COVID-19 lung is the first step towards identifying potential targets and therapies that disrupt some of the disease’s vicious circuits. In particular, targeting cells responsible for pulmonary fibrosis early on could possibly prevent or ameliorate long-term complications in survivors of severe COVID-19,” says Benjamin Izar, MD, PhD, assistant professor of medicine, who led a group of more than 40 investigators to complete in several months a series of analyses that usually takes years.
This study and a companion paper led by researchers at Harvard/MIT, to which the Columbia investigators also contributed, were published the journal Nature on April 29.
Study Creates Atlas of Cells in COVID Lung
The new study is unique from other investigations in that it directly examines lung tissue (rather than sputum or bronchial washes) using single-cell molecular profiling that can identify each cell in a tissue sample and record each cell’s activity, resulting in an atlas of cells in COVID lung.

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Do I Have to Get the Covid Vaccine in My Arm?

Most people will roll up their sleeves for the injection, but some may want to consider an alternate body part.By now most people are familiar with how the Covid-19 vaccine is typically administered: a quick jab to the upper arm. But there is a lesser known place on the body where the vaccine has also been approved for injection: the thigh.While getting the vaccine in the thigh is rare, there are some groups of people who may want to consider it. If you fall into one of the categories below and think you would be better off getting the Covid-19 vaccine in your thigh instead of your arm, it’s best to discuss it first with your doctor.Which adults might want to get a shot in the thigh?People with a history or risk of lymphedema in both arms.Lymphedema is a chronic and painful condition that causes swelling in parts of the body. It can develop in breast cancer patients, for example, who require surgery to remove lymph nodes from under the arm. Removal of the lymph nodes disrupts the flow of lymph, the extra fluid from tissues that would normally drain through the lymphatic system into the bloodstream, causing the fluid to back up and the breast, torso or arm to swell on the affected side.In both the Moderna and Pfizer-BioNTech clinical vaccine trials, some participants experienced swollen lymph nodes at the armpit or the neck region two to four days following vaccination, on the same side where the shot was administered in the arm. This is a normal short-term side effect that means the body is responding to the vaccine. In the case of Moderna, the median duration of swelling was one to two days, and it lasted an average of 10 days in those receiving Pfizer-BioNTech.For patients with lymphedema or at risk for lymphedema, however, this side effect could be concerning. If someone has lymphedema in both arms or if a patient is at risk of lymphedema in both arms, then some medical institutions are recommending that their patients get the Covid-19 vaccine in the thigh as a precautionary measure. The concern is that the vaccine could either make the arms swell even more or, for those who are at risk of lymphedema, create worrisome symptoms where there were none.The immune response might also be less efficient if the shot is administered in an arm without lymph nodes or one that has impaired lymphatic drainage.“The lymph vessels are responsible for draining fluid out of all of our tissues, so if your lymphatic drainage isn’t good, your tissues swell from fluid — and that would also mean you wouldn’t carry a vaccine very efficiently from tissue to lymph node,” said Marc Jenkins, director of the Center for Immunology at the University of Minnesota Medical School.Patients who had lymph nodes removed from one arm may get the vaccine in the unaffected arm rather than the thigh, said Cheryl Brunelle, the associate director of the Lymphedema Research Program at Massachusetts General Hospital in Boston.People who have (or had) breast cancer.Swollen lymph nodes in the armpit can be a sign of breast cancer. If someone with a history of breast cancer didn’t know that the Pfizer-BioNTech or Moderna vaccines can produce swollen lymph nodes, it could be “very scary for her, thinking it may be a recurrence,” Ms. Brunelle said.To alleviate potential concerns, people with a history of breast cancer can opt to get the vaccine in the thigh if they wish.People who need a mammogram within six weeks of their Covid-19 vaccine.Coronavirus vaccinations can cause enlarged lymph nodes in the armpit or near the collarbone that will show up as white blobs on mammograms and potentially be mistaken as a sign of cancer. The Society of Breast Imaging recommends trying to schedule your routine screening mammogram before your first Covid-19 vaccine dose or at least one month after your second vaccine dose. But an alternative plan would be to get the vaccine in your thigh instead.“Injection in thigh would be extremely unlikely to lead to armpit nodes swelling,” Dr. Constance D. Lehman, the chief of breast imaging at Massachusetts General Hospital, told The New York Times earlier this month.If you prefer to get the vaccine in your arm and have already scheduled your mammogram, you can keep that appointment — as well as your vaccine appointment — and call your breast imaging center ahead of time to let them know about the timing of your vaccine.If you received the Covid vaccine in the arm in the last six weeks, your radiologist will expect to see lymph node swelling on the same side that you received the vaccine. This would be a normal finding unless the swelling continued for more than six weeks or there were other clinical concerns; in that case they would take more images as needed, Ms. Brunelle said.Which vaccination sites offer thigh injections?This could take a little persistence. Covid-19 vaccine sites primarily give people arm vaccinations: It’s quick, efficient and there’s no need to find a private room to disrobe. Because the vast majority of people will receive arm injections, some vaccination sites may not have staff who are trained to inject in the thigh.“I just advise patients to call ahead, let the vaccine clinic know or the pharmacy know that they’re asking for the vaccine in the thigh,” Ms. Brunelle said. “I also counsel patients that if a local facility or practitioner giving the vaccine is not familiar with the thigh as an approved alternate site, the patient can share the C.D.C. Standing Orders document that lists the thigh as an alternative site for both the Pfizer and Moderna vaccines.”In New York City, people visiting health department vaccination sites can speak with staff if they have concerns about getting the vaccine in the arm, said Michael Lanza, a health department spokesman. These sites also have “quiet rooms” where thigh injections can be performed discreetly, he added, but “it should only be done when medically necessary.”What if I am a candidate for a thigh vaccine but I already had the vaccine injected in my arm?Experts say not to worry if you already got vaccinated on the side where you had breast cancer or if you were vaccinated in the arm that had fewer lymph nodes; what is important is that you received the vaccine.“We don’t want to scare women who already got vaccinated,” said Dr. Alphonse Taghian, director of the Lymphedema Research Program at Massachusetts General Hospital. “It is possible there will be no problem at all.”To learn more, Dr. Taghian and Ms. Brunelle will be surveying current and former breast cancer patients about the side effects of the vaccine to better understand how many patients report swollen lymph nodes, as well as when and how long the symptom occurs. They hope to have results before the end of the year.Dr. Taghian encourages patients with a history of cancer to contact their oncology team with questions or concerns, and to tell their doctor if they develop new signs of swelling.Why are the vaccines typically injected in the arm?The Covid-19 vaccines are designed to be injected into muscle, and the muscles of the upper arm are convenient for shots and thought to be less painful than some other areas of the body. But a vaccine can be injected into other muscles, provided they are near some of the hundreds of lymph nodes that exist in the body. The upper thigh, for example, is located near multiple lymph nodes and has already been shown to generate an effective immune response after vaccination.Lymph nodes are “absolutely critical for generating immune responses,” said Dr. Akiko Iwasaki, a professor of immunobiology at Yale University.When a vaccine enters the arm or thigh muscle, it gets carried into a nearby lymph node, she added. There, the vaccine is taken up by special cells that teach the white blood cells, known as T cells and B cells, to either become killer cells, which seek out and destroy coronavirus-infected cells, or antibody-secreting cells.Decades ago, other vaccines were often injected into the buttocks. But scientists now understand that the layers of fat cells in our bottoms are too numerous to allow easy access to the muscles and lymph, making the immune response inefficient. In addition, vaccination in the buttocks is generally not done to avoid injury to the sciatic nerve.

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Many Hispanics died of COVID-19 because of work exposure, study suggests

Hispanic Americans have died of COVID-19 at a disproportionately high rate compared to whites because of workplace exposure to the virus, a new study suggests.
It’s widely documented that Hispanics are overrepresented among workers in essential industries and occupations ranging from warehousing and grocery stores to health care and construction, much of which kept operating when most of the country shut down last spring.
The analysis of federal data showed that, considering their representation in the U.S. population, far higher percentages of Hispanics of working age — 30 to 69 years old — have died of COVID-19 than whites in the same age groups. A separate look at case estimates showed a similar pattern of unequally high COVID-19 infection rates for Hispanics — meaning that the elevated deaths in the working-age Hispanic population is consistent with elevated exposure to the virus.
“There was no evidence before this paper that really demonstrated that the excess cases were precisely in these working age groups,” said Reanne Frank, professor of sociology at The Ohio State University and co-author of the study.
“Particularly for front-line and essential workers, among whom Hispanics are overrepresented, COVID-19 is an occupational disease that spreads at work. Hispanics were on the front lines and they bore a disproportionate cost.”
Identifying a link between essential work and a higher rate of COVID-19 deaths should lead to better workplace protections, said study co-author D. Phuong (Phoenix) Do, associate professor of public health policy and administration at the University of Wisconsin-Milwaukee.

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Avocado discovery may point to leukemia treatment

A compound in avocados may ultimately offer a route to better leukemia treatment, says a new University of Guelph study.
The compound targets an enzyme that scientists have identified for the first time as being critical to cancer cell growth, said Dr. Paul Spagnuolo, Department of Food Science.
Published recently in the journal Blood, the study focused on acute myeloid leukemia (AML), which is the most devastating form of leukemia. Most cases occur in people over age 65, and fewer than 10 per cent of patients survive five years after diagnosis.
Leukemia cells have higher amounts of an enzyme called VLCAD involved in their metabolism, said Spagnuolo.
“The cell relies on that pathway to survive,” he said, explaining that the compound is a likely candidate for drug therapy. “This is the first time VLCAD has been identified as a target in any cancer.”
His team screened nutraceutical compounds among numerous compounds, looking for any substance that might inhibit the enzyme. “Lo and behold, the best one was derived from avocado,” said Spagnuolo.
Earlier, his lab looked at avocatin B, a fat molecule found only in avocados, for potential use in preventing diabetes and managing obesity. Now he’s eager to see it used in leukemia patients.
“VLCAD can be a good marker to identify patients suitable for this type of therapy. It can also be a marker to measure the activity of the drug,” said Spagnuolo. “That sets the stage for eventual use of this molecule in human clinical trials.”
Currently, about half of patients over 65 diagnosed with AML enter palliative care. Others undergo chemotherapy, but drug treatments are toxic and can end up killing patients.
“There’s been a drive to find less toxic drugs that can be used.”
Referring to earlier work using avocatin B for diabetes, Spagnuolo said, “We completed a human study with this as an oral supplement and have been able to show that appreciable amounts are fairly well tolerated.”
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More than 25% of infants not getting common childhood vaccinations

More than a quarter of American infants in 2018 had not received common childhood vaccines that protect them from illnesses such as polio, tetanus, measles, mumps and chicken pox, new research from the University of Virginia School of Medicine reveals.
Only 72.8% of infants aged 19-35 months had received the full series of the seven recommended vaccines, falling far short of the federal government’s goal of 90%. Those less likely to complete the vaccine series include African-American infants, infants born to mothers with less than a high-school education and infants in families with incomes below the federal poverty line.
The researchers warn that failure to complete the vaccine series leaves children at increased risk of infection, illness and death. It also reduces the herd immunity of the entire population, allowing diseases to spread more easily.
“These findings highlight that significant disparities still exist in protecting infants from preventable diseases in the United States,” said researcher Rajesh Balkrishnan, PhD, of UVA’s Department of Public Health Sciences. “The low seven-vaccine series rates in low-income families are disheartening, especially with federal programs such as Vaccine for Children, which provides coverage for their service.”
Trends in Childhood Vaccination
Some good news: There was a 30% increase in the overall number of infants getting the full vaccine series during 2009-2018, the 10-year period the researchers examined.
However, disparities in vaccine uptake grew between low-income families and higher-income families in that time. In 2009, families below the federal poverty line were 9% less likely to get the full vaccine series than families with annual income above $75,000. In 2018, low-income families were 37% less likely to complete the vaccine series.
The researchers say the lower rate among low-income families is especially disheartening considering the availability of federal programs such as Vaccine for Children, which provides free vaccines for uninsured, underinsured and Medicaid-eligible children.
“Free vaccination coupled with no physician administration fees, linked with potential programs that are frequently accessed by low-income families, could be a potential solution to increase immunization rates,” Balkrishnan said “The role of healthcare professionals such as pharmacists could also be expanded to provide these services cost effectively.”
The study found that mothers who had not completed high school were almost 27% less likely to have their infants fully vaccinated than moms with college education. That disparity had increased sharply from a previous study evaluating 1995-2003. The previous study found that mothers with less than high-school education were 7.8% less likely to complete the vaccine series.
Among African-Americans, completion of the vaccine series was significantly lower than in both whites and Hispanics. The researchers call this disparity “unacceptable” and say cost-effective interventions are needed to increase immunization rates and address vaccine hesitancy.
“These findings are particularly important in the context of the current COVID pandemic,” Balkrishnan said. “Particular attention needs to be paid to vulnerable populations in ensuring the availability and access to important life-saving vaccines.”
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Materials provided by University of Virginia Health System. Note: Content may be edited for style and length.

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