Publisher Health

Tuberculosis (TB) is a potentially serious infectious disease caused by a type of bacterium called Mycobacterium tuberculosis. The bacteria usually affect the lungs, but also can invade other organs.
In 2018, tuberculosis bacteria infected 1.7 billion people – roughly 23% of the world’s population, according to the Centers for Disease Control and Prevention (CDC). In 2020, the CDC reported 7,174 TB cases and 13 million people living with a latent tuberculosis infection (the germs are in the body but do not cause sickness) in the United States.
Even after successful therapy for tuberculosis, survivors of the disease have an increased risk of recurrent infection and death. A new study published recently by researchers at Baylor College of Medicine found that the cells of humans and animals who have recovered from tuberculosis had prematurely aged up to 12 to 14 years.
“It’s possible that this premature cellular aging is one reason why survivors of tuberculosis have a high risk of mortality,” said Dr. Andrew DiNardo, assistant professor of infectious diseases at Baylor College of Medicine and senior author of the paper.
To measure the aging of the cells, researchers looked at the epigenetic clock of the cells. Epigenetics looks at how the DNA inside every cell is coiled. As we age, how the DNA is coiled changes, and severe infection is changing it in such a way to increase premature aging.
In this study, the researchers studied multiple cohorts and multiple tissue types, and discovered that tuberculosis induced perturbations in epigenetic regulation, specifically in the regulation mediated by DNA methylation. These changes correlated with oxidative stress-induced senescence and was associated with premature cellular aging. These processes were conserved across both guinea pigs and humans.

Five grams of plastic particles on average enter the human gastrointestinal tract per person per week. This is roughly equivalent to the weight of a credit card. Whether ingested micro- and nanoplastics pose a health risk is being investigated in numerous studies but is largely unknown to date. A research team from MedUni Vienna has now summarised the current state of scientific knowledge. The review article has just been published in the journal Exposure & Health.
Medical research on the topic centres on the digestive system where micro- and nanoplastic particles (MNPs) can be found in tissue. Experimental studies indicate that ingested MNPs passing through the gastrointestinal tract lead to changes in the composition of the gut microbiome. The research team led by Elisabeth Gruber (Division of Visceral Surgery of MedUni Vienna’s Department for General Surgery) and Lukas Kenner (Department of Pathology MedUni Vienna, Comprehensive Cancer Center (CCC) MedUni Vienna and Vienna General Hospital, Department of Laboratory Animal Pathology of VetMedUni) report that such changes are associated with the development of metabolic diseases such as diabetes, obesity or chronic liver disease.
In addition to the effects on the gut microbiome, scientists also described specific molecular mechanisms that facilitate the uptake of MNPs into gut tissue. Using specific analyses, it was shown that MNPs in the gastrointestinal tract could increasingly be taken up into tissue under certain physicochemical conditions and activate mechanisms involved in local inflammatory and immune responses. Nanoplastics in particular are associated with biochemical processes that are crucially involved in carcinogenesis.
Plastic particles also in drinking water
Nanoplastics are defined as being less than 0.001 millimetre in size, while microplastics, at 0.001 to 5 millimetres, are to some extent still visible to the naked eye. MNPs enter the food chain from packaging waste, among other sources. The plastic particles are not only trafficked into the body via food such as marine life or sea salt in particular, drinking also plays a part. According to a study, anyone who drinks the recommended 1.5 to two litres of water a day from plastic bottles ingests around 90,000 plastic particles per year in this way alone. However, those who choose tap water can, depending on their geographical location, reduce the amount ingested to 40,000 plastic particles. Researchers also demonstrated widespread contamination of mineral water with xenohormones leached from PET (polyethylene terephthalate) bottles. Xenohormones are known to exhibit oestrogenic activity which can act carcinogenic in the body.
The potential adverse health effects of plastic particles could be particularly impactful for people with a chronic disease burden, says Lukas Kenner. “A healthy gut is more likely to ward off the health risk. But local changes in the gastrointestinal tract, such as those present in chronic disease or even negative stress, could make them susceptible to the harmful effects of MNPs.”
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Mayo Clinic researchers have validated a new antibody test to diagnose multiple sclerosis (MS), a potentially disabling disease of the brain and spinal cord. Nearly 1 million people in the U.S. are affected by MS, according to the National Multiple Sclerosis Society.
An antibody typically consists of two immunoglobulin heavy chains and two light chains. There are two types of light chains: kappa and lambda. The validated test measures kappa immunoglobulin free light chains in cerebrospinal fluid. The authors conclude the test is a valid alternative to a commonly used test to detect oligoclonal bands in cerebrospinal fluid, according to findings published in Mayo Clinic Proceedings. Oligoclonal bands are proteins that indicate inflammation of the central nervous system.
“Among the advantages of kappa measurement is that it’s a much easier test to run in the laboratory,” says Ruba Saadeh, a research fellow in neuroimmunology in Mayo Clinic’s Department of Laboratory Medicine and Pathology, and the study’s first author. “Our findings represent a cost savings as well as an automated alternative to the arsenal of tests used to diagnose multiple sclerosis.”
MS is a disease that affects the brain and spinal cord, and can lead to deterioration and permanent damage of the nerves. While its cause is unknown, the disease triggers the immune system to attack the protective coating on nerve fibers. This disrupts signals between the brain and spinal cord. Symptoms vary widely. These symptoms depend on the amount of nerve damage and which nerves are affected. Symptoms can be temporary or long-lasting.
While no cure for MS has been found, treatments can speed recovery from attacks and manage symptoms.
The diagnostic test that detects oligoclonal bands in cerebrospinal fluid requires about four hours of analytical processing. This test is labor-intensive and involves subjective visual interpretation. The Mayo study validates a diagnostic value of 0.1 milligrams per deciliter to measure kappa free light chains. The study’s results are comparable to diagnostic values from tests measuring oligoclonal bands.
The study analyzed serum samples from a retrospective cohort of 702 Mayo patients to determine a diagnostic value for measurement of kappa free light chains. Samples from a prospective cohort of 657 Mayo patients were used to validate that value. Of the more than 1,300 patients, 12% were diagnosed with MS.
“Kappa free light chain measurement in cerebrospinal fluid is relatively new, and various published studies have attempted to decide what is the best medical decision point for optimal performance of the test,” says Maria Alice Willrich, Ph.D., a Mayo Clinic pathologist and the study’s senior author. “Based on our study data, we identified the optimal performance of the test for a large U.S.-based population.”
The study estimates a significant cost savings for the new test. Better yet, results are available in about 20 minutes.
“The laboratory technologist training can be standardized because of the automation involved in this process, and the subjective visual interpretation of bands and personnel involvement is substantially reduced,” Dr. Willrich says.
The study was funded in part by Mayo Clinic’s Department of Laboratory Medicine and Pathology and was supported by a grant from the National Center for Advancing Translational Sciences. The authors report no competing interests.
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Materials provided by Mayo Clinic. Original written by Jay Furst. Note: Content may be edited for style and length.

In the epic battle between hosts and viruses, viruses are constantly evolving to be more infectious. Now, researchers from Japan have found that human genes also evolve to help protect our bodies from invasion by life-threatening viruses.
In a study published in December in Journal of Virology, researchers from Tokyo Medical and Dental University (TMDU) have revealed that a monkey variant of human immunodeficiency virus (HIV) can counteract a human protein that defends against viral infection in a different way than it counteracts the same protein in monkeys.
Simian immunodeficiency virus (SIV) is closely related to HIV, and both viruses tend to use similar strategies to escape their hosts’ defenses, which also tend to be very similar. One of these defenses is a protein called tetherin (also known as BST-2 or CD317). If a cell is invaded by the virus, tetherin prevents the virus from leaving the cell and infecting other nearby cells. To counter this measure, HIV and SIV make a protein called viral protein U (Vpu) that attaches to tetherin and blocks its effects.
“Because viruses adapt to their hosts, HIV Vpu is most effective against human tetherin, while SIV Vpu is most effective against monkey tetherin,” explains Dr. Takeshi Yoshida, senior author of the study. “But in at least one unusual case, a strain of SIV that typically infects the greater spot-nosed monkey can also overcome human defenses, which suggests that SIV potentially infects humans.”
To explore how SIV Vpu affects human tetherin, the researchers mutated different parts of the protein and looked at how well it blocked tetherin’s normal activities and effects.
“The results were unexpected,” says Dr. Weitong Yao, lead author. “We discovered that the parts of SIV Vpu that are needed to counteract monkey tetherin are not the same as the parts needed to counteract human tetherin.”
The researchers pinpointed seven specific amino acids (the basic building blocks of proteins) that are needed for SIV to block human tetherin. Importantly, these seven amino acids were not essential for the virus to block monkey tetherin.
“What this tells us is that SIV Vpu may use a totally distinct mechanisms to counteract the effects of monkey and human tetherin,” says Yoshida.
Given the different approaches that this viral protein uses to neutralize monkey and human tetherin, it seems likely that the gene encoding human tetherin faced different pressures over the course of evolution than the gene encoding monkey tetherin. The results from this study could help us better understand the evolution of host genes as a result of host-pathogen interactions.
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Researchers from North Carolina State University and the University of North Carolina at Chapel Hill have developed an implantable biotechnology that produces and releases CAR-T cells for attacking cancerous tumors. In a proof-of-concept study involving lymphoma in mice, the researchers found that treatment with the implants was faster and more effective than conventional CAR-T cell cancer treatment.
T cells are part of the immune system, tasked with identifying and destroying cells in the body that have become infected with an invading pathogen. CAR-T cells are T cells that have been engineered to identify cancer cells and destroy them. CAR-T cells are already in clinical use for treating lymphomas, and there are many clinical trials under way focused on using CAR-T cell treatments against other forms of cancer.
“A major drawback to CAR-T cell treatment is that it is tremendously expensive — hundreds of thousands of dollars per dose,” says Yevgeny Brudno, corresponding author of the study and assistant professor in the joint biomedical engineering department at NC State and UNC.
“Due to its cost, many people are shut out from this treatment. One reason for the high cost is that the manufacturing process is complex, time-consuming and has to be tailored to each cancer patient individually,” Brudno says. “We wanted to address challenges in CAR-T treatment related to both manufacturing time and cost.”
“Reducing the manufacturing time is even more critical for patients with rapidly progressing disease,” says Pritha Agarwalla, lead author of the study and a postdoctoral researcher in the joint biomedical engineering department.
To tackle this challenge, the researchers created a biotechnology called Multifunctional Alginate Scaffolds for T cell Engineering and Release (MASTER). The work was done in partnership with Gianpietro Dotti, professor in the Department of Microbiology and Immunology and co-leader of the Immunology Program at the Lineberger Cancer Center at UNC; and Frances Ligler, a professor of biomedical engineering at Texas A&M University.

Chimeric antigen receptor (CAR) T cells can be remarkably effective in treating leukemias and lymphomas, but there are no successful immunotherapies for neuroendocrine tumors (NETs) and gastrointestinal cancers (GICs) yet. Researchers at Penn Medicine have discovered that CAR-T cells directed to a tumor antigen, CDH17, a cell surface marker expressed on both NETs and GICs but also found on healthy tissues, eliminated GICs in several preclinical models without toxicity to normal tissues in multiple mouse organs, including the small intestine and colon. The results from this study, the first to target CDH17 in neuroendocrine tumors, suggest a new class of tumor associated antigens accessible to CAR-T cells in tumors but sequestered from CAR-T cells in healthy tissues.
In the study, published March 21 in Nature Cancer, researchers isolated a llama-derived nanobody, a small antibody, which led to the identification of CDH17. Targeting CDH17 — which, in humans as in mice, is mainly expressed in the intestinal system — with CDH17CAR T cells eliminated gastric, pancreatic, and colorectal cancers in mouse models. While CDH17 is also expressed in normal intestinal epithelial cells, the CDH17CAR T cells did not attack the normal cells, likely because the CAR T cells cannot reach or bind to healthy tissue in the tight junction between normal intestine epithelial cells, creating a “masking” effect in healthy cells from CAR T attack.
“Our work demonstrates that CDH17CAR T cells can eliminate solid tumors like NETs and GICs, but do not damage healthy, normal tissues that also express CDH17, because CDH17 is sequestered and hidden between the normal cells,” said senior author Xianxin Hua, MD, PhD, a professor in the Department of Cancer Biology in the Abramson Family Cancer Research Institute at Penn. “This opens avenues to explore a new class of tumor antigens that are also expressed in normal cells but protected by the CAR T cell attack and is hopefully another important step in developing safer immunotherapies for solid tumors.”
GICs and NETs are often fatal once they have spread. There are about five million new cases of GICs annually worldwide, underscoring the need for scientific and clinical advancements.
“Now that we have identified CDH17 as a promising new class target, we can take a multipronged approach to target CDH17 and launch a phase 1 study to treat drug-resistant NETs and GICs,” said first author Zijie Feng, a research scientist in the department of Cancer Biology at Penn. “The CDH17 CAR T cells may be particularly suitable for patients with solid tumors, and these findings motivate additional investigation of CAR Ts that can be developed against previously written-off tumor-associated antigens.”
Other Penn researchers on the study include Carl H. June, MD, the Richard W. Vague Professor in Immunotherapy in the Department of Pathology and Laboratory Medicine; Bryson Katona, MD, PhD, director of the Gastrointestinal Cancer Genetics Program; Terence P. Gade, MD, PhD, co-director of the Penn Image-Guided Interventions Laboratory; and David C. Metz, MBBCh, a professor CE of Medicine in the Divison of Gastroenterology and Hepatology.
In 2021, the University of Pennsylvania and Chimeric Therapeutics, Limited entered into an exclusive licensing agreement for the first CDH17 CAR T cell therapy to be explored for clinical research.
This study was funded by a Care for Carcinoid Foundation Research Grant and a Neuroendocrine Tumor Research Foundation (NETRF) Accelerator Grant.
Note: Penn has licensed certain Penn-owned intellectual property to Chimeric Therapeutics, Limited. (“Chimeric”), and the Perelman School of Medicine at the University of Pennsylvania receives sponsored research funding from Chimeric in support of Dr. Hua’s laboratory. Penn and Drs. Hua and Feng are entitled to receive future financial benefits from development and commercialization of technologies licensed and optioned to Chimeric.
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Antibiotic resistance is a growing problem worldwide that threatens the efficacy of available treatments and can lead to extended hospital stays and increased mortality. Researchers have long sought ways to address the problem. Given that antibiotic use fuels resistance, reducing antibiotic use offers an appealing strategy for curbing resistance.
“It makes sense intuitively,” said epidemiologist Melinda Pettigrew, Ph.D, at the Yale School of Public Health in New Haven, Conn., but limited data exist on how treatment duration affects resistance genes. The ultimate goal, she said, is to find an optimal dosage that reduces the use of antibiotics without compromising the health of patients.
But it can be done, suggests a study published this week in mBio, an open-access journal of the American Society for Microbiology. Pettigrew and her colleagues studied data from a randomized controlled trial of children who had been diagnosed with community-acquired pneumonia (CAP) and treated with beta-lactam antibiotics. The children were participants in a multi-institutional, NIH-funded study called SCOUT-CAP (NCT02891915), which found that a 5-day course of beta-lactam antibiotics was as effective as the standard 10-day course in treating CAP. Pettigrew led the microbiome substudy of the SCOUT-CAP trial.
For their substudy, Pettigrew and her colleagues wanted to track how the 2 treatment durations influenced antibiotic resistance genes and respiratory microbiota. They conducted shotgun metagenomic sequencing on DNA from throat swabs and stool samples collected from the children at 2 points — first, a few days after diagnosis with CAP, and then at the conclusion of the trial, a few weeks later.
Sequencing revealed fewer resistance genes in children who had received the 5-day treatment regimen compared to those who received the 10-day regimen. Some of those genes were associated with resistance to beta-lactam, which the researchers expected. Surprisingly, the longer antibiotic course also led to a significant increase in resistance genes associated with multiple other antibiotics. “You can have increases in resistance to drugs other than the one you’re treating with,” she said. “There are all these off-target effects.” The researchers also found that treatment duration changed the population of commensal bacteria in different ways.
“So antibiotics don’t just impact the pathogens that we’re trying to treat,” Pettigrew said. “They can affect the microbiota as a whole.”
The SCOUT-CAP trial — including this substudy — followed patients for 30 days. In future studies, Pettigrew said she’d like to study the clinical implications of antibiotic treatment over a longer term. “We know that antibiotics disrupt the microbiome and increase susceptibility to other pathogens,” she said, “but don’t have a measure of that risk.” The study also didn’t measure how long the effects persist. “We don’t know if the resistome [the collection of resistance genes in bacteria] and the microbiome will eventually return to normal.”
These kinds of studies could help researchers harness the microbiome to identify patients most at risk of antibiotic resistance. “If future investigations support these findings, these techniques could someday aid the FDA in determining drug safety profiles and establishing optimal treatment durations.
“The microbiome is so important for health, and disruption can lead to other downstream effects, including antibiotic resistance,” Pettigrew said.
The research reported here was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1AI104681. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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Researchers at the George Washington University published findings from the world’s largest cohort study showing that hospitalized patients with moderate COVID-19 who were given aspirin early on in their treatment had a lower risk of dying compared to patients who were not given aspirin.
Lead researcher, Jonathan Chow said, “This is our third study and the culmination of 15 months of work looking at aspirin use in hospitalized COVID-19 patients. We continue to find that aspirin use is associated with improved outcomes and lower rates of death in hospitalized patients. What’s more, it’s low cost and readily available, which is important in parts of the world where more expensive therapeutics might not be as accessible.”
The study included the largest data set of 112,269 patients hospitalized with moderate COVID-19. The data included patients enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health’s National COVID Cohort Collaborative (N3C).
Researchers found a 1.6% reduction in mortality when aspirin was given within the first day of hospitalization in patients with moderate disease severity and that patients were less prone to forming blood clots. They also found that elderly patients and patients with one or more comorbidities especially benefit from early aspirin therapy.
Keith Crandall, Director of the Computational Biology Institute (CBI) at George Washington University, the organization that helped assemble and input GW’s data into the NIH database and curate the dataset into a usable format for the statistical analysis, said, “This research is vital to providing physicians and patients effective and accessible COVID-19 treatments to help reduce in-hospital mortality rates and help people recover from this potentially devastating disease.”
Chow and his team have been focused on this topic since the beginning of the pandemic. Their first study published in April 2021 and the second study published in November 2021.
This latest study, “Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19” will be published on March 24 in JAMA Network Open.
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Vaccination against COVID-19 during pregnancy is not associated with a higher risk of pregnancy complications, according to a large-scale registry study from Karolinska Institutet in Sweden and the Norwegian Institute of Public Health published in the journal JAMA.
The study, which comprised almost 160,000 pregnancies, found no increase in the risk of preterm birth, growth retardation, low Apgar scores at birth or the need for neonatal care after vaccination against COVID-19 during pregnancy.
“The results are reassuring and can hopefully make pregnant individuals more willing to get vaccinated,” says co-first author Anne Örtqvist Rosin, researcher at the Department of Medicine, Karolinska Institutet (Solna).
Earlier studies have shown that pregnant women belong to a risk group for serious COVID-19 requiring intensive care with a higher risk of death than non-pregnant women of a fertile age. Pregnant women with severe COVID-19 are also more likely to have preterm births. Since January 2021, efficacious COVID-19 vaccines have been available in Sweden and Norway, and in May 2021 Sweden recommended all pregnant individuals to have a COVID-19 jab, followed in August by Norway.
“We’re still seeing that vaccination rates are lower than in the rest of the population, so it’s likely that there’s some concern about how the vaccines affect the pregnant individual and the fetus,” explains Dr Örtqvist Rosin. “When the vaccines were produced, pregnant women were not included in the large clinical studies, and until now there have been no population-based data about any risk there might be to them.”
The researchers linked Sweden’s Pregnancy Register and Norway’s Medical Birth Register to each country’s vaccination register to obtain data on if and when pregnant individuals were vaccinated and with which vaccine. The study included a total of 157,521 individuals who gave birth between January 2021 and January 2022, of whom almost one fifth (18 per cent) had been vaccinated. It was found that vaccinated individuals were at no higher risk than unvaccinated of developing one of the studied complications.
The majority of the pregnant individuals included in the study were vaccinated after week 12 in accordance with current recommendations. 95 per cent received an mRNA vaccine (Pfizer-BioNTech or Moderna). This should be taken into consideration when interpreting the results, which were similar for the different mRNA vaccines irrespective of whether one or two doses were given. Vaccination during the third trimester and vaccination with the Moderna vaccine was associated with a slightly lower risk of neonatal care.
One potential advantage of vaccination during pregnancy is that the antibodies thus formed pass through the placenta, providing the newborn baby with a certain degree of protection against COVID-19.
“We’re now planning to study how long this protection lasts, and if SARS-CoV-2 infection or vaccination during pregnancy has any other lasting effects on the child’s health,” says joint last author Professor Olof Stephansson at the Department of Medicine, Karolinska Institutet (Solna).
The study was a collaboration between researchers at Sweden’s Karolinska Institutet and the Norwegian Institute of Public Health. It was supported by grants from the Research Council of Norway, NordForsk and the European Research Council (ERC). Co-author and KI researcher Rickard Ljung has received a fee from Pfizer beyond the scope of this study and is an employee of the Swedish Medical Products Agency. No other potential conflicts of interest have been reported.
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As food moves through the digestive tract, contracting muscles along the tract keep things flowing smoothly. Loss of this motility can lead to acid reflux, failure of food to move out of the stomach, or constipation.
Dysmotility disorders are usually diagnosed with a catheter containing pressure transducers, which can sense contractions of the GI tract. MIT researchers have now designed a new device that could offer a cheaper and easier-to-manufacture alternative to existing diagnostics for GI dysmotility, inspired by the design of an ancient Incan technology, the quipu — a set of knotted cords used to communicate information.
In animal tests, the MIT researchers and their collaborators at Brigham and Women’s Hospital showed that their simple device, a silicone tube filled with liquid metal and knotted many times, produces measurements similar to those generated by the state-of-the-art diagnostic technique, known as high-resolution manometry.
“This is a really simple, inexpensive setup, yet we’re able to make a measurement that typically would require devices that cost thousands of dollars and require an instrument that is much more complicated,” says Giovanni Traverso, who is the Karl van Tassel Career Development Assistant Professor of Mechanical Engineering at MIT, a gastroenterologist at Brigham and Women’s Hospital, and the senior author of the study.
MIT research scientists Kewang Nan and Sahab Babaee are the lead authors of the study, which appears today in Nature Biomedical Engineering.
Diagnosing dysmotility
Contractions of the gastrointestinal tract are critical for moving food all the way through the tract, and interruptions of these contractions at any point can cause health problems. The gold-standard manometry diagnostic can be used to measure whether the muscles of the GI tract are working properly to generate those waves.