Publisher Health

An unhealthy gut triggers changes in normal breast tissue that helps breast cancer spread to other parts of the body, new research from UVA Cancer Center reveals.
The gut microbiome — the collection of microbes that naturally live inside us — can be disrupted by poor diet, long-term antibiotic use, obesity or other factors. When this happens, the ailing microbiome reprograms important immune cells in healthy breast tissue, called mast cells, to facilitate cancer’s spread, UVA Health’s new discovery shows.
The finding could help scientists develop ways to keep breast cancer from metastasizing (spreading to other parts of the body). When it does, it is often deadly: Only 29% of women with metastatic breast cancer survive five years; for men with metastatic breast cancer, that figure is just 22%.
The discovery could also let doctors predict which patients are at greatest risk of cancer recurrence after treatment, the UVA scientists say.
“We show gut commensal dysbiosis, an unhealthy and inflammatory gut microbiome, systemically changes the mammary tissues of mice that do not have cancer. The tissue changes enhance infiltration of mast cells that, in the presence of a tumor, facilitate breast tumor metastasis,” said researcher Melanie R. Rutkowski, PhD, of UVA Cancer Center and the University of Virginia School of Medicine. “Mast cells recruited into the tissue environment during dysbiosis restructure the tissue architecture in such a way that tumor cells metastasize to other organs.”
The Microbiome and Breast Cancer
Rutkowski has been a pioneer in unveiling the surprising relationship between gut health and breast cancer. Her latest work reveals complex interactions between our gut microbes and mast cells in the breast. Mast cells are blood cells which help regulate the body’s immune response to disease and allergens. Rutkowski’s new work suggests that the gut microbiome can systemically influence mast cell behavior and function in the presence of tumors.

Up to 1 in 5 women in the postpartum period will experience a mental health disorder like postpartum depression or generalized anxiety disorder.
How an organization handles a mother’s return to work can have a significant impact on her mental health, according to new research from the University of Georgia.
Organizations control the majority of work-related factors that predict better mental health outcomes. This can include access to paid maternity leave, total workload, and job flexibility.
But previous research examining maternal mental health with respect to work has lumped return to work in with maternity leave, said lead author Rachel McCardel, a doctoral student in UGA’s College of Public Health.
“But return to work is more than that because, while maternity leave is an important resource, it doesn’t necessarily capture the actual process of when leave ends and when you start resuming work, and when you start combining your roles as an employee and a mother,” she said.
Understanding the role that return to work plays in a working mother’s mental health may help navigate solutions. It will point to where interventions or support could prevent or lessen the burden of conditions like depression or anxiety.

Expensive ongoing treatment for cancer and diabetes are the best-known drivers of the medical debt that contributes to two-thirds of personal bankruptcies, but a Rutgers study indicates other chronic conditions contribute significantly, too.
Asthma, heart disease, lung disease, anxiety and other mood disorders are all associated with elevated rates of medical debt, according to an analysis of data from 9,174 households that participated in the 2019 wave of the Panel Study of Income Dynamics (PSID). The study was published in Preventive Medicine.
“Medical debt has frequently been connected to cancer and, more recently, to diabetes. The important finding here is that medical debt is connected to a wide range of chronic conditions,” said Irina Grafova, lead author of the study and an assistant professor at the Rutgers School of Public Health. “The other important finding is that this connection between chronic disease and medical debt exists at all income levels. It is not confined to lower-income households. It also holds true for middle-income and higher-income households, so it really is a society-wide issue.”
The PSID, which began in 1968, conducted its 2019 wave of questionnaires in English and Spanish between Feb. 28, 2019, and Jan. 8, 2020. It covers a representative sample of U.S. households and contains data on household income, medical debt, demographics, disease and health behaviors.
The study team separated households by income levels: lower (less than double the census poverty threshold), middle (two to four times the threshold) and higher (more than four times the threshold). Team members then calculated the correlation between 11 chronic conditions and two financial conditions: any reported medical debt or more than $2,000 in reported medical debt.
The chronic conditions most strongly associated with medical debt were the following: Heart disease, asthma and anxiety disorders (in lower-income households) Diabetes, lung disease, and mood disorders (in middle-income households) Cancer, lung disease, arthritis, and mood disorders (in higher income households)Rates of any medical debt were 8.74 percent in lower-income households, 9.77 percent in middle-income households and 4.6 percent in higher-income households. Rates of medical debt greater than $2,000 — a number that previous research pegs as the threshold where serious financial problems often begin — were 5.82 percent in lower-income households, 6.46 percent in middle-income households and 3.05 percent in higher-income households.
Future research from the same team will delve deeper into the connection between chronic ailments and medical debt, explore how the COVID-19 pandemic affected medical debt and explore strategies for reducing medical debt.
“We’re eager to see the data from PSID’s 2021 wave, so we can see how COVID affected debt levels,” Grafova said. “The pandemic itself and our response to it were so large and multifaceted that it’s impossible to predict. Did COVID-related health care costs and higher unemployment increase medical debt, or did stimulus payments and decreased expenditures on things like restaurants and vacations allow Americans to reduce their medical debt? We still don’t know the answers, but we should know them soon.”
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Materials provided by Rutgers University. Original written by Andrew Smith. Note: Content may be edited for style and length.

When you’re cooking or cleaning inside your home, what chemicals are you breathing, and are they potentially harmful? Colorado State University chemists have given us a solid start on the answer.
A large, collaborative research experiment that attempted to map the airborne chemistry of a typical home took place in 2018 and was co-led by Delphine Farmer, associate professor in the Department of Chemistry at CSU. The experiment, called HOMEChem, brought 60 scientists from 13 universities to a test house at the University of Texas at Austin to perform typical home activities like cooking and cleaning and to use sophisticated instrumentation to document the chemistry that resulted. The effort, called HOMEChem, was supported by the Sloan Foundation.
In a new paper in Environmental Science & Technology, Farmer’s team at CSU has taken the massive amounts of data collected during HOMEChem and sorted it out by health effects. They identified how many compounds they observed that are known human toxins, or, based on newer Environmental Protection Agency models, predicted to be likely human toxins. Most such compounds are emitted in low quantities and can be cleared through proper ventilation. But the health impacts of both the individual compounds and their complex mixtures indoors are not well understood by scientists.
The bottom line? “Indoor air isn’t going to kill you, but we do find that indoor air has many more – and often times at higher levels — known and potential air toxics versus outdoors, particularly when you’re cooking,” said Farmer, an atmospheric chemist who, before this experiment, had spent the majority of her career measuring more “traditional,” outdoor air toxics.
Data management
The feat of data management for meaningfully connecting the data from HOMEChem to toxins databases was led by co-author Anna Hodshire, a former CSU postdoctoral researcher with skill in analyzing data from atmospheric instrumentation.

An engineered CRISPR-based method that finds RNA from SARS-CoV-2, the virus that causes COVID-19, promises to make testing for that and other diseases fast and easy.
Collaborators at Rice University and the University of Connecticut further engineered the RNA-editing CRISPR-Cas13 system to boost their power for detecting minute amounts of the SARS-CoV-2 virus in biological samples without the time-consuming RNA extraction and amplification step necessary in gold-standard PCR testing.
The new platform was highly successful compared to PCR, finding 10 out of 11 positives and no false positives for the virus in tests on clinical samples directly from nasal swabs. The researchers showed their technique finds signs of SARS-CoV-2 in attomolar (10-18) concentrations.
The study led by chemical and biomolecular engineer Xue Sherry Gao at Rice’s George R. Brown School of Engineering and postdoctoral researchers Jie Yang of Rice and Yang Song of Connecticut appears in Nature Chemical Biology.
Cas13, like its better-known cousin Cas9, is part of the system by which bacteria naturally defend themselves against invading phages. Since its discovery, CRISPR-Cas9 has been adapted by scientists to edit living DNA genomes and shows great promise to treat and even cure diseases.
And it can be used in other ways. Cas13 on its own can be enhanced with guide RNA to find and snip target RNA sequences, but also to find “collateral,” in this case the presence of viruses like SARS-CoV-2.

Research on decomposition often focuses on environmental factors like temperature or humidity, but researchers at the University of Tennessee in Knoxville have taken a closer look at contributions from inside the body. One factor that may play an important role is the body mass index (BMI) of a decomposing body, they report this week in  mSphere, a journal of the American Society for Microbiology.
The researchers investigated how intrinsic factors like disease, BMI or medication load affected microbial life at the university’s body donation research facility, specifically established for the decomposition of human remains. They analyzed the bacterial and fungal composition of fluids produced by 19 human bodies, as well as the composition of the surrounding soil, during “active decomposition,” which lasts until the carcass stops releasing fluids and the abdomen cavity collapses.
For the new study, they found that in the soil beneath and near individuals who were underweight (BMI less than 18.5) and normal weight (a BMI between 18.5 and 26), the diversity decreased in bacterial  communities. In obese and overweight individuals (with BMIs above 26), the diversity remained mostly constant. 
“We think about BMI as a proxy for how much fat versus how much muscle we have in our body,” said microbial ecologist Jennifer DeBruyn, Ph.D, at the University of Tennessee’s Anthropology Research Facility, which is also known as the “Body Farm.” Those 2 biological tissues have different chemical compositions that may affect the soil differently.
“We know from plant litter studies that even slight changes in tissue chemistry can change the microbial decomposers,” she said. More fat tissue — in a body with higher BMI — means more moisture and a higher ratio of carbon to nitrogen, relative to a body with a lower BMI. 
The study began, DeBruyn said, with observations by researchers who’d worked for years with decomposing bodies at the Body Farm. They noticed that bodies donated and placed on the soil  at the same time didn’t change in the same way over time. “The bodies experienced identical environmental conditions, but we saw big differences in how quickly they decomposed,” DeBruyn said. That suggested that something within the body, rather than in the environment, contributed to the process. 
For the  mSphere  study, the researchers studied 19 bodies that had been donated and placed in the outdoor facility between February 2019 and March 2020. The ages of the donors ranged from 40-91, with a mean of 71, and the BMIs ranged from 14.2-55.1. Temperature and humidity data were recorded hourly by remote tags, and the researchers collected soil samples at regular intervals throughout decomposition. They also used syringes to collect samples of fluids that had been released by the bodies and pooled in the soil. 

If you’ve had COVID-19, it may still be messing with your brain. Those who have been infected with the virus are at increased risk of developing a range of neurological conditions in the first year after the infection, new research shows. Such complications include strokes, cognitive and memory problems, depression, anxiety and migraine headaches, according to a comprehensive analysis of federal health data by researchers at Washington University School of Medicine in St. Louis and the Veterans Affairs St. Louis Health Care system.
Additionally, the post-COVID brain is associated with movement disorders, from tremors and involuntary muscle contractions to epileptic seizures, hearing and vision abnormalities, and balance and coordination difficulties as well as other symptoms similar to what is experienced with Parkinson’s disease.
The findings are published Sept. 22 in Nature Medicine.
“Our study provides a comprehensive assessment of the long-term neurologic consequences of COVID-19,” said senior author Ziyad Al-Aly, MD, a clinical epidemiologist at Washington University. “Past studies have examined a narrower set of neurological outcomes, mostly in hospitalized patients. We evaluated 44 brain and other neurologic disorders among both nonhospitalized and hospitalized patients, including those admitted to the intensive care unit. The results show the devastating long-term effects of COVID-19. These are part and parcel of long COVID. The virus is not always as benign as some people think it is.”
Overall, COVID-19 has contributed to more than 40 million new cases of neurological disorders worldwide, Al-Aly said.
Other than having a COVID infection, specific risk factors for long-term neurological problems are scarce. “We’re seeing brain problems in previously healthy individuals and those who have had mild infections,” Al-Aly said. “It doesn’t matter if you are young or old, female or male, or what your race is. It doesn’t matter if you smoked or not, or if you had other unhealthy habits or conditions.”
Few people in the study were vaccinated for COVID-19 because the vaccines were not yet widely available during the time span of the study, from March 2020 through early January 2021. The data also predates delta, omicron and other COVID variants.

Nanoengineers at the University of California San Diego have developed microscopic robots, called microrobots, that can swim around in the lungs, deliver medication and be used to clear up life-threatening cases of bacterial pneumonia.
In mice, the microrobots safely eliminated pneumonia-causing bacteria in the lungs and resulted in 100% survival. By contrast, untreated mice all died within three days after infection.
The results are published Sept. 22 in Nature Materials.
The microrobots are made of algae cells whose surfaces are speckled with antibiotic-filled nanoparticles. The algae provide movement, which allows the microrobots to swim around and deliver antibiotics directly to more bacteria in the lungs. The nanoparticles containing the antibiotics are made of tiny biodegradable polymer spheres that are coated with the cell membranes of neutrophils, which are a type of white blood cell. What’s special about these cell membranes is that they absorb and neutralize inflammatory molecules produced by bacteria and the body’s immune system. This gives the microrobots the ability to reduce harmful inflammation, which in turn makes them more effective at fighting lung infection.
The work is a joint effort between the labs of nanoengineering professors Joseph Wang and Liangfang Zhang, both at the UC San Diego Jacobs School of Engineering. Wang is a world leader in the field of micro- and nanorobotics research, while Zhang is a world leader in developing cell-mimicking nanoparticles for treating infections and diseases. Together, they have pioneered the development of tiny drug-delivering robots that can be safely used in live animals to treat bacterial infections in the stomach and blood. Treating bacterial lung infections is the latest in their line of work.
“Our goal is to do targeted drug delivery into more challenging parts of the body, like the lungs. And we want to do it in a way that is safe, easy, biocompatible and long lasting,” said Zhang. “That is what we’ve demonstrated in this work.”
The team used the microrobots to treat mice with an acute and potentially fatal form of pneumonia caused by the bacteria Pseudomonas aeruginosa. This form of pneumonia commonly affects patients who receive mechanical ventilation in the intensive care unit. The researchers administered the microrobots to the lungs of the mice through a tube inserted in the windpipe. The infections fully cleared up after one week. All mice treated with the microrobots survived past 30 days, while untreated mice died within three days.

Using the wrong mathematical formula to assess heartbeat rhythms may lead oncologists to inappropriately stop life-saving chemotherapy, according to research findings from UNC Lineberger Comprehensive Cancer Center scientists. Standardizing the mathematical formulas for measuring heartbeat rhythms with electrocardiograms, and avoiding one commonly used formula, could reduce this unintended outcome, the researchers reported.
The study findings were published in JAMA Oncology.
The formulas in this study are based on how the cardiac system recharges itself after each heartbeat. In reading an electrocardiogram (ECG), heartbeat spikes and bumps, called P through U waves, indicate when the heart is contracting and relaxing. The interval between the start of the Q wave and end of the T wave, when prolonged, is of most concern for people receiving chemotherapy. When the heart muscle takes a comparatively longer time to contract and relax than usual, which is known as QT prolongation, it may increase the risk of developing abnormal heart rhythms that can lead to sudden cardiac arrest.
Because QT prolongation is a potentially serious side effect, every chemotherapy drug goes through rigorous testing for QT prolongation in its approval process. Many chemotherapy agents that prolong the QT interval today fall into a class known as targeted therapies. As the use of targeted therapies expands, monitoring QT prolongation becomes even more important, especially for many blood cancers that are often treated with targeted drugs, such as those that were part of this study.
In their study of different formulas, the researchers discovered that one formula, the Bazett formula, was associated with a three-fold increase in the corrected QT interval compared to other formulas used with oncology patients. The overestimation of the QT interval by the Bazett formula can potentially lead to misguided chemotherapy modification that can impact clinical care.
“The mathematics that determine a QT formula matters because if an inappropriate formula is used, it could lead oncologists to reduce chemotherapy unnecessarily and possibly affect the potential for cure,” said Daniel R. Richardson, MD, MSc, assistant professor of medicine at UNC Lineberger and corresponding author of the article. “The differences we found between QT formula were pretty striking and we did not anticipate the magnitude of difference when we started this project. It certainly has changed how I treat patients.”
The researchers looked at medical records of 6,881 adult cancer patients who received 24 different types of chemotherapy between 2010 and 2020. The patients were seen at the North Carolina Basnight Cancer Hospital and received nearly 20,000 ECGs.
The investigators found that the Bazett formula resulted in longer QT prolongation periods than two other formulas (Framingham and Fridericia) in 40.9% of ECGs examined; this was concerning as Bazett is the default formula used with many ECG devices.
“We initially discovered this problem while treating a patient with acute promyelocytic leukemia with arsenic trioxide, a drug known to cause QT prolongation. We realized that there was inconsistent guidance about how to assess the QT interval with this drug and what values should lead to dose reductions,” said senior author Joshua F. Zeidner, MD, an associate professor of medicine and chief of leukemia research at UNC Lineberger. “The clinical protocol that ultimately led to the approval of this drug used a very specific QT formula — Framingham — and we were using a different formula — Bazett — to guide our treatment decisions. Prior to this discovery, most of us were not aware that there were multiple formulas available for corrected QT intervals. The findings from this study have been practice changing as we no longer recommend the Bazett formula for clinical guidance.”
For their next steps, the researchers are considering conducting a study evaluating oncologists’ and pharmacists’ awareness of the different QT prolongation formulas and their impact as this would help researchers better grasp the magnitude of the issue. Primarily, though, the researchers want to advocate for an understanding of the effect of formula choice on outcomes and to advocate for standardization when assessing oncology patients.

A common, spontaneous mutation in blood stem cells, which has been linked to higher risks of blood cancer and cardiovascular disease, may promote these diseases by altering the stem cells’ programming of gene activity and the mix of blood cells they produce, according to a study co-led by investigators at Weill Cornell Medicine, NewYork-Presbyterian, the New York Genome Center, Harvard Medical School and Dana-Farber Cancer Institute.
The blood stem cell mutation, known as DNMT3A R882, leads to the growth of a large population, or “clonal outgrowth,” of circulating blood cells that also contain this mutation. In general, such mutant outgrowths become increasingly common with age, and are thought to represent a very early, pre-malignant stage of cancer development. However, the molecular details of how they arise have been hard to pin down, because the mutant cells broadly look and function the same as normal cells. In the study, which appears Sept. 22 in Nature Genetics, the researchers surmounted this challenge to illuminate the effects of R882 mutations in DNMT3A, the most commonly mutated gene in blood cells.
“These findings help us understand how these mutated cells outgrow normal cells, and pave the way for possible future interventions targeting these cells to prevent cancers and other clonal outgrowth-related conditions,” said study senior author Dr. Dan Landau, associate professor of medicine in the Division of Hematology and Medical Oncology, associate professor of physiology and biophysics and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, a core faculty member of the New York Genome Center and an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center.
The study was a collaboration between Dr. Landau’s laboratory and the laboratory of Dr. Irene Ghobrial, professor of medicine at Harvard Medical School and the Dana Farber Cancer Institute. Dr. Ghobrial’s team supplied samples of blood stem cells from the marrow of patients in remission from multiple myeloma — patients in which, they have found, blood cell clonal outgrowths are relatively common.
Dr. Landau’s team evaluated more than 6,000 cells from the patients, using “single-cell multi-omics” techniques to detect the DNMT3A R882 mutation, and to map gene activity and chemical marks on DNA called methylations, programming marks that switch off nearby genes. In this way, they recorded in unprecedented detail how the mutation-containing blood stem cells differed from their normal counterparts.
The researchers found, for example, that the mutant stem cells’ production of mature blood cells was skewed towards red blood cells and the cells that make blood-clotting platelets — providing potential rationales underlying the higher risk of cardiovascular disease in patients with clonal outgrowths in their blood.
The gene DNMT3A normally encodes an enzyme called a methyltransferase, which helps place methylations on DNA. The researchers found that the mutation’s disruption of normal methylation led to a lack of these “off switches” across the genome and the abnormal activation of key genes. The latter included inflammation-driving genes and cancer-associated growth genes — all consistent with a growth and survival advantage for the mutant cells, and a higher risk of their progression to cancer.
“Our hope is that by uncovering molecular signatures like these we’ll be able to target these clonal outgrowths and prevent cancer development in people who are still healthy,” said study co-first-author Dr. Anna Nam, assistant professor of pathology and laboratory medicine in the Department of Pathology and Laboratory Medicine and a member of the Meyer Cancer Center at Weill Cornell Medicine, and a pathologist at NewYork-Presbyterian/Weill Cornell Medical Center.
The researchers plan to do further studies of clonal outgrowths resulting from other mutations. They are also developing their multi-omics techniques to increase the speed and scale of these studies.
“We should soon be able to do studies of many more cells at a time, giving us a more complete picture of what is going on,” said co-first author Neville Dusaj, a Tri-institutional MD-PhD Program student in the Landau laboratory.
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Materials provided by Weill Cornell Medicine. Note: Content may be edited for style and length.