Publisher Health

New research led by a team at Massachusetts General Hospital (MGH) points to a promising strategy to boost tumors’ intake of cancer drugs, thereby increasing the effectiveness of chemotherapy treatments. The group’s findings are published in Nature Nanotechnology.
Getting enough anticancer drugs into a tumor is often difficult, and a potential strategy to overcome this challenge involves binding the medications to albumin, the most abundant protein in blood. The strategy relies on tumors’ large appetite for protein nutrients that fuel malignant growth. When consuming available albumin, the tumors will inadvertently take in the attached drugs.
A popular albumin-bound drug approved by the U.S. Food and Drug Administration is nanoparticle albumin-bound paclitaxel (nab-PTX), and it has been successfully used to treat late-stage lung and pancreatic cancers. “Not all patients respond to nab-PTX, though, and the effectiveness of its delivery to tumors has been mixed, owing to an incomplete understanding of how albumin impacts drug delivery and actions,” says senior author Miles Miller, PhD, a principal investigator in the MGH Center for Systems Biology and assistant professor of Radiology at Harvard Medical School.
To provide insights, Miller and his colleagues assessed the delivery of nab-PTX to tumors at a single-cell resolution in mouse models of cancer. Using 3D microscopy and what’s called tissue clearing technology, the team found that cancer cells can take up a significant amount of nab-PTX, and that the consumption of these drugs is controlled by signaling pathways that are involved in the cells’ uptake of nutrients such as albumin.
“This discovery suggested that if we could manipulate these pathways, we might be able to trick cancer cells into a nutrient-starved state, thereby enhancing their consumption of nab-PTX,” explains Ran Li, PhD, first author on the study and an instructor in the MGH Department of Radiology and the Center for Systems Biology. Indeed, treating tumors with an inhibitor of insulin-like growth factor 1 receptor, an important component of one of the signaling pathways, improved the accumulation of nab-PTX in tumors and boosted its effectiveness.
“These results offer new possibilities to improve delivery of albumin-bound drugs in patients with diverse types of cancer,” says Miller.
Co-senior author Ralph Weissleder, MD, PhD, is director of the MGH Center for Systems Biology. Other co-authors from MGH include Thomas Ng, MD, PhD, Mark Prytyskach, Chris Rodell, PhD, Hannes Mikula, PhD, Rainer Kohler, PhD, Michelle Garlin, MD, Sareh Parangi, MD, Nabeel Bardeesy, PhD, and colleagues at multiple other institutions.
Support for this work was provided by the National Institutes of Health, the National Cancer Institute, the National Science Foundation, the American Cancer Society, the American Thyroid Association and the Thyroid Cancer Survivors’ Association.
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Materials provided by Massachusetts General Hospital. Note: Content may be edited for style and length.

Just a few weeks ago people sneaked across state lines, designed websites to scour the internet and even tried to pay for coronavirus vaccination appointments.Now, in much of the United States, getting vaccinated can be as easy as walking into a pharmacy. Earlier this week, President Biden called for pharmacies to provide vaccinations on a walk-in basis as a way to encourage hesitant people to get the shot. He also announced a new federal website and phone number that will help people find the site closest to them. “We’re going to make it easier than ever to get vaccinated,” Mr. Biden said Tuesday.Chains like Walmart, Walgreens, Safeway and Stop & Shop have said that they are now offering vaccines to walk-in clients at some locations or in mobile clinics. Other pharmacies preceded the president’s announcement. Rite Aid said that it would accommodate walk-ins on a limited basis last week, for example. The Biden administration is broadening access to help meet a goal of getting at least the first shot to 70 percent of American adults by July 4. Many of the chains qualified the offer, noting that walk-ins would be subject to availability and that it was better to schedule an appointment, even on the same day.Federal health officials have also directed drugstores and grocery-store pharmacies to offer second doses of the vaccine to people who received their first shot from a different provider.The Biden administration is hoping for an uptick in vaccinations ahead of the Food and Drug Administration’s expected authorization of the Pfizer-BioNTech vaccine for adolescents ages 12 to 15 by early next week. The president has said that age group is important in the fight against the virus because while they are not as susceptible to severe illness, they can still get sick and infect others.Convenience is not the only way officials have encouraged people to get vaccinated. In exchange for a free inoculation against a potentially deadly illness you can now receive a ticket to a baseball game, a stiff drink or $100.

Early on in the COVID-19 pandemic, health officials seized on contact tracing as the most effective way to anticipate the virus’s migration from the initial, densely populated hot spots and try to curb its spread. Months later, infections were nonetheless recorded in similar patterns in nearly every region of the country, both urban and rural.
A team of environmental engineers, alerted by the unusual wealth of data published regularly by county health agencies throughout the pandemic, began researching new methods to describe what was happening on the ground in a way that does not require obtaining information on individuals’ movements or contacts. Funding for their effort came through a National Research Foundation RAPID research grant (CBET 2028271).
In a paper published May 6 in the Proceedings of the National Academy of Sciences, they presented their results: a model that predicts where the disease will spread from an outbreak, in what patterns and how quickly.
“Our model should be helpful to policymakers because it predicts disease spread without getting into granular details, such as personal travel information, which can be tricky to obtain from a privacy standpoint and difficult to gather in terms of resources,” explained Xiaolong Geng, a research assistant professor of environmental engineering at NJIT who built the model and is one of the paper’s authors.
“We did not think a high level of intrusion would work in the United States so we sought an alternative way to map the spread,” noted Gabriel Katul, the Theodore S. Coile Distinguished Professor of Hydrology and Micrometeorology at Duke University and a co-author.
Their numerical scheme mapped the classic SIR epidemic model (computations based on a division of the population into groups of susceptible, infectious and recovered people) onto the population agglomeration template. Their calculations closely approximated the multiphase COVID-19 epidemics recorded in each U.S. state.

In the brain of a person with Alzheimer’s disease, neurons degenerate and die, slowly eliminating memories and cognitive skills. However, not all neurons are impacted equally. Some types of neurons in certain brain regions are more susceptible, and even among those subtypes — mysteriously — some perish and some do not.
Researchers at Gladstone Institutes have uncovered molecular clues that help explain what makes some neurons more susceptible than others in Alzheimer’s disease. In a study published in the journal Nature Neuroscience, the scientists present evidence that neurons with high levels of the protein apolipoprotein E (apoE) are more sensitive to degeneration, and that this susceptibility is linked to apoE’s regulation of immune-response molecules within neurons.
“This is the first time such a link has been established, which is quite exciting and could open new paths to developing treatments for Alzheimer’s disease,” says Gladstone Senior Investigator Yadong Huang, MD, PhD, senior author of the study.
Finding Clues by Comparing Individual Neurons
ApoE has long been a focus of Alzheimer’s disease research because people carrying a gene that produces a particular form of apoE (called apoE4) have a higher risk of developing the disease. For this study, Huang and his team harnessed recent advancements in single-cell analysis to study the potential role of apoE in the variable susceptibility of neurons in Alzheimer’s disease.
Specifically, they applied a technique known as single-nucleus RNA sequencing, which reveals the extent to which the different genes in any given cell are expressed and converted into RNA, the intermediate between genes and proteins. This approach allowed them to compare individual cells within a cell type, as well as across different cell types.

People who feel younger have a greater sense of well-being, better cognitive functioning, less inflammation, lower risk of hospitalization and even live longer than their older-feeling peers. A study published by the American Psychological Association suggests one potential reason for the link between subjective age and health: Feeling younger could help buffer middle-aged and older adults against the damaging effects of stress.
In the study, published in Psychology and Aging, researchers from the German Centre of Gerontology analyzed three years of data from 5,039 participants in the German Ageing Survey, a longitudinal survey of residents of Germany age 40 and older. The survey included questions about the amount of perceived stress in peoples’ lives and their functional health — how much they were limited in daily activities such as walking, dressing and bathing. Participants also indicated their subjective age by answering the question, “How old do you feel?”
The researchers found, on average, participants who reported more stress in their lives experienced a steeper decline in functional health over three years, and that link between stress and functional health decline was stronger for chronologically older participants.
However, subjective age seemed to provide a protective buffer. Among people who felt younger than their chronological age, the link between stress and declines in functional health was weaker. That protective effect was strongest among the oldest participants.
“Generally, we know that functional health declines with advancing age, but we also know that these age-related functional health trajectories are remarkably varied. As a result, some individuals enter old age and very old age with quite good and intact health resources, whereas others experience a pronounced decline in functional health, which might even result in need for long-term care,” said study lead author Markus Wettstein, PhD, who is now at University of Heidelberg. “Our findings support the role of stress as a risk factor for functional health decline, particularly among older individuals, as well as the health-supporting and stress-buffering role of a younger subjective age.”
The results suggest that interventions that aim to help people feel younger could reduce the harm caused by stress and improve health among older adults, according to the researchers — though further study is needed to help determine what kind of interventions would work best. For example, Wettstein said, messaging campaigns to counteract ageism and negative age stereotypes and to promote positive views on aging could help people feel younger. In addition, more general stress-reduction interventions and stress management training could prevent functional health loss among older adults, according to Wettstein.
Finally, more research is needed to figure out the ideal gap between subjective and chronological age, according to Wettstein, as previous research has suggested that it’s helpful to feel younger up to a point but that benefits decrease as the gap between subjective and chronological age increases. “Feeling younger to some extent might be adaptive for functional health outcomes, whereas ‘feeling too young’ might be less adaptive or even maladaptive,” he said.
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Materials provided by American Psychological Association. Note: Content may be edited for style and length.

A team of researchers from UCLA, Cedars-Sinai and the Cystic Fibrosis Foundation has developed a first-of-its-kind molecular catalog of cells in healthy lungs and the lungs of people with cystic fibrosis.
The catalog, described today in the journal Nature Medicine, reveals new subtypes of cells and illustrates how the disease changes the cellular makeup of the airways. The findings could help scientists in their search for specific cell types that represent prime targets for genetic and cell therapies for cystic fibrosis.
“This new research has provided us with valuable insights into the cellular makeup of both healthy and diseased airways,” said Dr. Brigitte Gomperts, a co-senior author of the study and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. “If you can understand how things work in a state of health, it becomes easier to see what cellular and molecular changes occur in a disease state.”
A progressive genetic disorder that affects more than 70,000 people worldwide, cystic fibrosis results from mutations to the CFTR gene. Cells that contain the defective protein encoded by the gene produce unusually thick and sticky mucus that builds up in the lungs and other organs. This mucus clogs the airways, trapping germs and bacteria that can cause life-threatening infections and irreversible lung damage.
While several new therapies can partially restore the function of these damaged proteins, easing symptoms of the disease, slowing its progression and improving quality of life, these treatments only work in people with some of the many CFTR mutations that can cause cystic fibrosis.
“We have made tremendous progress in the development of treatments for the underlying cause of cystic fibrosis, but many people cannot benefit from these medicines,” said John (Jed) Mahoney, a senior co-author of the paper and head of the stem cell biology team at the Cystic Fibrosis Foundation Therapeutics Lab. “This research provides critical insight into how the disease alters the cellular makeup of the airways, which will enable scientists to better target the next generation of transformative therapies for all people with cystic fibrosis.”
The research team was assembled through the Cystic Fibrosis Foundation’s Epithelial Stem Cell Consortium, which brings together scientists from across the U.S. in an ongoing effort to identify different subtypes of stem cells in the lungs and study their function. Because these cells can self-renew and produce a continuous supply of specialized cells that maintain, repair and regenerate the airways, therapies aimed at correcting CFTR mutations in stem cells hold the best hope for a one-time, universal treatment for the disease.

In a study published in the Journal of the American Medical Association (JAMA), Johns Hopkins Medicine researchers show that although two doses of a vaccine against SARS-CoV-2 — the virus that causes COVID 19 — confers some protection for people who have received solid organ transplants, it’s still not enough to enable them to dispense with masks, physical distancing and other safety measures.
This is a follow-up study to an earlier one published in March in JAMA, in which the researchers reported that only 17% of the participating transplant recipients produced sufficient antibodies after just one dose of a two-dose COVID-19 vaccine regimen.
“While there was an increase in those with detectable antibodies — 54% overall — after the second shot, the number of transplant recipients in our second study whose antibody levels reached high enough levels to ward off a SARS-CoV-2 infection was still well below what’s typically seen in people with healthy immune systems,” says study lead author Brian Boyarsky, M.D., a surgery resident at the Johns Hopkins University School of Medicine.
“Based on our findings, we recommend that transplant recipients and other immunocompromised patients continue to practice strict COVID-19 safety precautions, even after vaccination,” Boyarsky says.
People who receive solid organ transplants (such as hearts, lungs and kidneys) often must take drugs to suppress their immune systems and prevent rejection. Such regimens may interfere with a transplant recipient’s ability to make antibodies to foreign substances, including the protective ones produced in response to vaccines.
The new study evaluated this immunogenic response following the second dose of either of the two messenger RNA (mRNA) vaccines — made by Moderna and Pfizer-BioNTech — for 658 transplant recipients, none of whom had a prior diagnosis of COVID-19. The participants completed their two-dose regimen between Dec. 16, 2020, and March 13, 2021.

Researchers at North Carolina State University and the University of North Carolina Greensboro made a surprising finding while examining areas where sand flies rear their young: a new species of bacteria that is highly attractive to pregnant, or gravid, sand flies. The findings could advance the production of ecologically safe baits or traps to reduce sand fly populations.
Sand flies are vectors for important parasitic diseases affecting people in tropical and subtropical regions in Asia, Africa and the Middle East. One of those diseases is Leishmaniasis, which generally causes sores and skin ulcers but in some cases can detrimentally affect internal organs.
“Sand flies live in sheltered places such as animal burrows, caves, and rock or tree crevices, so it’s difficult to reach them with insecticides,” said Loganathan Ponnusamy, principal research scholar in NC State’s Department of Entomology and Plant Pathology and the corresponding author of a paper describing the research. “If you’re able to attract sand flies with a chemical that attracts them in nature, you’re better able to target and kill them.”
The research team, which included researchers from Gideon Wasserberg’s lab at the University of North Carolina Greensboro, cultured a number of different bacterial species from the sand fly larval rearing area and found one that hadn’t yet been identified: Sphingobacterium phlebotomi, a new member of the family of bacteria known as Sphingobacteriaceae.
To prove that the bacterium hadn’t already been identified, Madhavi Kakumanu, an NC State research scholar, performed a number of tests — including scanning electron microscopy, chemical analysis and whole genome sequencing — and showed the bacterium’s novelty.
“We were culturing and isolating a lot of different bacteria and found this new one almost by accident,” Kakumanu, the paper’s first author, said.
Bahjat Fadi Marayati, a graduate student in Wasserberg’s lab, conducted attraction tests and demonstrated that this new bacteria species produces volatile chemicals that were attractive to pregnant sand flies.
Pregnant sand flies preferred the smell of the new bacterium over other chemical compounds presented during testing, Ponnusamy said, showing that the bacterium acted as a beacon for an appropriate place for females to lay eggs.
Ponnusamy says further testing will be done to narrow down even further the chemical compounds that attract sand flies.
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Materials provided by North Carolina State University. Original written by Mick Kulikowski. Note: Content may be edited for style and length.

As the human body’s largest organ, the skin is responsible for protecting against a wide range of possible infections on all fleshy surfaces, from head to toe. So how exactly does the skin organize its defenses against such an array of threats?
A new Yale study shows that the epidermis, the outermost layer of skin, is comprised of an army of immune cells that station themselves at regular intervals across the skin’s vast expanse to resist infection. When necessary, the researchers found, these immune system soldiers are able to reposition themselves to protect vulnerable areas.
The study, published in the journal Nature Cell Biology, was conducted by the lab of Valentina Greco, the Carolyn Walch Slayman Professor of Genetics, at Yale School of Medicine.
“It’s a surveillance system with two separate roles,” said Catherine Matte-Martone, manager of the Greco lab manager and co-first author of the study. “The skin controls the sentinels by mediating their numbers based on its own density, while they in turn provide dynamic coverage to prevent cracks in the skin’s defenses.”
The epidermis contains two main types of immune system cells, Langerhans cells (LCs) and dendritic epidermal T cells (DETCs). In the study, the research team led by Matte-Martone and Sangbum Park, a researcher from Michigan State University (MSU), captured images of these immune system cells interacting with epithelial cells, the closely packed skin cells that comprise most of the epidermis.
They found that the immune system cells are distributed in a distinct pattern, maintaining a minimum distance between the individual cells. According to the researchers, these immune cells seem to have the ability to avoid each other, preventing clusters in any locations and maintaining a consistent distribution.
The phenomenon is similar to a property observed in neurons, in which scientists have observed a tendency of neurons from a single branch to avoid each other.
“Our study suggests that LCs and DETCs appear to have a mechanism of ‘self-avoidance,’, similar to neuronal cells,” said Park, an assistant professor at MSU and former postdoctoral fellow in the Greco lab at Yale.
When the team removed some immune cells in one area, they observed that the remaining cells were able to reposition across the skin tissue to defend the gaps in coverage. They also found that they could disrupt the normal distribution of those cells by knocking out a gene known as Rac1 (Ras-related C3 botulinum toxin substrate 1), which regulates projections on immune cells called dendrites. This process, they hypothesize, helps maintain the distance between immune cells.
The findings illustrate how specialized cell types can cooperate to carry out a larger role within the body.
“It is fascinating to observe how these different cell types co-exist and interact together in a developmental context rather than an immunological one,” Martone said.
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Materials provided by Yale University. Original written by Bill Hathaway. Note: Content may be edited for style and length.

Asthma attacks account for almost 50 percent of the cost of asthma care which totals $80 billion each year in the United States. Asthma is more severe in Black and Hispanic/Latinx patients, with double the rates of attacks and hospitalizations as the general population.
When the COVID-19 pandemic swept over the United States, a series of reports suggested that fewer people were coming to emergency departments for all sorts of medical problems, including asthma attacks and even heart attacks. In the case of asthma, it was not clear if the drop was due to people avoiding emergency services or due to better asthma control. A new analysis from investigators at Brigham and Women’s Hospital shines new light on this question. In a report of data collected as part of a trial in Black and Hispanic/Latinx patients with asthma that began before COVID-19 hit the U.S., they found total asthma attacks decreased by greater than 40 percent with the onset of the pandemic. Results are published in the Journal of Allergy & Clinical Immunology: In Practice.
“We found a substantial decrease in asthma exacerbation — on the order of what we see for biologic therapies for severe asthma,” said lead author Justin Salciccioli, MBBS, MA, a fellow in the Division of Pulmonary and Critical Care Medicine at the Brigham. “Although we don’t know for sure who in the cohort changed their behavior, it’s likely that decreased exposure to environmental or viral triggers contributed to our findings.”
While no single change is likely to account for the large decrease in asthma attacks, Salciccioli and colleagues note that decreased exposure to allergens such as pollen, dust mites and mold, as well as viruses like influenza, are most likely to account for the decrease in asthma attacks. During the pandemic, measures to decrease exposure to the virus that causes COVID-19, including wearing masks, physical distancing and more, may have also decreased exposure to triggers of asthma.
Salciccioli and colleagues analyzed data collected as part of the PREPARE (The PeRson EmPowered Asthma Relief) Trial. The PREPARE Trial, led by Elliot Israel, MD, the Gloria M. and Anthony C. Simboli Distinguished Chair in Asthma Research and director of Clinical Research in the Brigham’s Pulmonary and Critical Care Division, is a national randomized trial examining interventions to reduce asthma attacks in Black and Hispanic/Latinx adults with moderate-to-severe asthma supported by PCORI (The Patient Centered Outcome Research Institute). As part of the study, its nearly 1,200 participants completed monthly questionnaires remotely for 15 months, either online, by phone or by mail.
“Since patients participated remotely once they were enrolled, they could tell us about the condition of their asthma separate from any concerns about leaving the house or having contact with health care providers” said Israel.
This allowed the team to assess the impact of the COVID-19 pandemic independent of hesitancy to utilize health care.
To better understand how the pandemic may have affected people with asthma, the research team compared asthma exacerbation rates between the winter and spring of 2019 with those from 2020. There was a 40 percent decrease between the winter (Jan. 1 to March 31) and spring (April 1 to June 30) for 2020 compared to 2019. Participants who worked outside of the home when they first enrolled in the study had a 65 percent decrease. Decreases were also greatest for individuals with a less “allergic type” of asthma known as “TH2-low” asthma — a type of asthma that might be triggered by environmental irritants such as pollution, smoke, or ozone, as opposed to exposure to allergens such as dust mite or mold.
While this study included only Black and Hispanic/Latinx participants, those groups are among the most impacted by asthma.
“This is the first study to assess asthma exacerbation before and after the COVID-19 pandemic using data that are unlikely to be affected by patients avoiding the health care system,” said Salciccioli. “Because this was part of a prospective trial that started before the pandemic and was planned to be remote, it gave us a unique window into how changes during the pandemic may have led to a dramatic decrease in asthma exacerbation.”
The PeRson EmPowered Asthma RElief (PREPARE) trial is supported by a Patient-Centered Outcomes Research Institute (PCORI) Project Program Award (PCS-1504-30283). There were no additional funds for this work. All statements in this work represent the work of the authors and do not represent the views of PCORI, the Board of Governors or Methodology Committee.
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