Publisher Health

A promising approach to control Staphylococcus aureus bacterial colonization in people — using a probiotic instead of antibiotics — was safe and highly effective in a Phase 2 clinical trial. The new study, reported in The Lancet Microbe, found that the probiotic Bacillus subtilis markedly reduced S. aureus colonization in trial participants without harming the gut microbiota, which includes bacteria that can benefit people. The research was conducted by researchers at the National Institutes of Health led by Michael Otto, Ph.D., an NIH senior investigator at the National Institute of Allergy and Infectious Diseases (NIAID).
Methicillin-resistant S. aureus, or MRSA, is familiar to many people as a cause of serious disease. Less well known is that S. aureus often lives in the nose, on the body and in the gut without causing any harm. However, if the skin barrier is broken, or the immune system compromised, these colonizing bacteria can cause serious skin, bone, lung, and blood infections.
The prevention of S. aureus infections using approaches to “decolonize” the body has gained increased attention as the spread of antibiotic resistance limits treatment options. Some decolonization strategies are controversial because they also require large amounts of antibiotics, raising concerns about damage to the microbiota and the development of antibiotic resistance. So far, it appears that only nasal S. aureus colonization can be targeted with topical antibiotics without doing too much harm, but bacteria quickly can recolonize in the nose from the gut.
Probiotics, digestive supplements containing live microorganisms, may be a way to complement or replace antibiotics. Probiotic Bacillus is especially promising because it is administered orally as spores that can survive passage through the stomach and then temporarily grow in the intestine. In prior studies, Dr. Otto’s group discovered an S. aureus sensing system needed for S. aureus to grow in the gut. They also found that fengycins, Bacillus lipopeptides that are part peptide and part lipid, prevent the S. aureus sensing system from functioning, thereby eliminating the bacteria.
In the clinical trial, conducted in Thailand, the research team tested whether this approach works in people. They enrolled 115 healthy participants, all of whom were colonized naturally with S. aureus. A group of 55 people received B. subtilis probiotic once daily for four weeks; a control group of 60 people received a placebo. After four weeks researchers evaluated the participants’ S. aureus levels in the gut and nose. They found no changes in the control group, but in the probiotic group they observed a 96.8% S. aureus reduction in the stool and a 65.4% reduction in the nose.
“The probiotic we use does not ‘kill’ S. aureus, but it specifically and strongly diminishes its capacity to colonize,” Dr. Otto said. “We think we can target the ‘bad’ S. aureus while leaving the composition of the microbiota intact.”
The researchers also found that levels of S. aureus bacteria in the gut far exceeded S. aureus in the nose, which for decades has been the focus of staph infection prevention research. This finding adds to the potential importance of S. aureus reduction in the gut.
“Intestinal S. aureus colonization has been evident for decades, but mostly neglected by researchers because it was not a viable target for antibiotics,” Dr. Otto said. “Our results suggest a way to safely and effectively reduce the total number of colonizing S. aureus and also call for a categorical rethinking of what we learned in textbooks about S. aureus colonization of the human body.”
The researchers plan to continue their work by testing the probiotic in a larger and longer trial. They note that their approach probably does not work as quickly as antibiotics, but can be used for long periods because the probiotic as used in the clinical trial does not cause harm. Study collaborators in Thailand are from Rajamangala University of Technology Srivijaya, and Prince of Songkla University.

Cells jostling for a spot in a germinal center face a cutthroat admissions process. Formed after exposure to a pathogen or vaccine, germinal centers act as a kind of immune system training academy, helping B cells refine their response to the threat. Only B cells with the highest affinity for the pathogen or vaccine gain entry to these structures, where they undergo waves of mutations to produce successively stronger antibodies.
But one quirk of this process has long puzzled scientists: germinal centers appear to change the criteria for admission over time. In the later stages of a germinal center’s existence, B cells with little or no affinity for the virus flood the once exclusive site, ultimately comprising up to 30 percent of its graduates. Now, a new study in Cell describes this phenomenon in detail and suggests that high-affinity B cells — the same ones that sideline inferior B cells in the early stages — trigger this about-face in late-stage germinal centers. The findings shed new light on how the immune system mounts a response against infections such as COVID and HIV.
“Germinal centers are open structures that continuously receive B cells,” says Michel C. Nussenzweig, the Zanvil A. Cohn and Ralph M. Steinman Professor at Rockefeller. “As time goes on, the threshold for joining is lowered, and this leads to a more diverse set of responder cells.”
Inside a germinal center
For the study, Nussenzweig and colleagues tracked B cells in germinal centers in mice. They first demonstrated that, in early-stage germinal centers, B cells enter based on their ability to bind to a vaccine antigen. Since there is a limited supply of antigen in the area, high-affinity B cells (those with receptors especially adept at binding the antigen) nab an antigen and are duly admitted into the germinal center. Lower affinity B cells are left bumbling about outside.
How, then, do these low-affinity antibodies gain entry in the late-stage germinal center? Upon further investigation, the team found that, in the late-stage germinal center, elite B cells start churning out antibodies that bind to dendritic cells presenting antigen. A dense forest of antigen-antibody complexes start to clog the area, and the equivalent of a molecular traffic jam ensues. The upshot is that formerly scarce antigen is suddenly ripe for the taking. Low-affinity B cells bind whatever antigen is lying around, and that’s their ticket into the germinal center.

Paradoxically, this means that the same high-affinity B cells that shoulder low-affinity B cells out of the germinal center in the early stages ultimately set in motion the very process by which those inferior cells are ultimately admitted. “Our paper not only outlines and documents this phenomenon,” Nussenzweig says. “It shows that the mechanism by which it happens is antibody-dependent.”
A double-edge sword
In theory, introducing naive B cells into the germinal center accomplishes one of the larger goals of the immune system. “Diversity is a key feature of immunity,” Nussenzweig says. “The immune system as a whole does many things to maximize diversity, and here germinal centers are striving for a diverse immune response by lowering the threshold and letting more cells join.”
Naive B cells, which have less time to mutate when they invade the late-stage germinal center, will inevitably come out different than those elite B cells that were there all along. Whether that sort of diversity in the range of immune cells that encounter the pathogen helps or hinders depends on the virus in question. “It can be a very positive or very negative thing,” Nussenzweig says.
Take SARS-CoV-2, a virus with multiple bits of antigen (known as epitopes) that antibodies can use to identify the virus and latch on. After leaving the germinal center, naive B cells produce different antibodies than mature ones, which will attach to different epitopes — each attacking the virus from its own angle. If the virus mutates to render one antibody less effective or obsolete, the others can provide coverage. “Diversity gives you more targets, and you can make antibodies to other parts of the molecule,” Nussenzweig says. “For SARS viruses, it’s terrific, and in part responsible for our ability to fight off variants when we do get infected”
Not so with HIV, a virus with precious few epitopes. As Nussenzweig and colleagues described in a recent study, the body shuts down the production of an entire line of antibodies if it detects a surplus of minimally effective antibodies. Here, a diverse response increases the likelihood of low-affinity antibodies binding one of HIV’s only epitopes poorly, which could cause the body to take a vast component of the immune response offline. Similar antibodies that would have worked better may never be allowed to form. “For HIV, it gets in the way of an effective vaccine” Nussenzweig says.
The team hopes that their findings will inform future attempts at vaccine development, while also rounding out immunologists’ understanding of how the body responds to disease.

A new study finds a steady drop since 1945 in disruptive feats as a share of the world’s booming enterprise in scientific and technological advancement.Miracle vaccines. Videophones in our pockets. Reusable rockets. Our technological bounty and its related blur of scientific progress seem undeniable and unsurpassed. Yet analysts now report that the overall pace of real breakthroughs has fallen dramatically over the past almost three-quarters of a century.This month in the journal Nature, the report’s researchers told how their study of millions of scientific papers and patents shows that investigators and inventors have made relatively few breakthroughs and innovations compared with the world’s growing mountain of science and technology research. The three analysts found a steady drop from 1945 through 2010 in disruptive finds as a share of the booming venture, suggesting that scientists today are more likely to push ahead incrementally than to make intellectual leaps.“We should be in a golden age of new discoveries and innovations,” said Michael Park, an author of the paper and a doctoral candidate in entrepreneurship and strategic management at University of Minnesota.The new finding of Mr. Park and his colleagues suggests that investments in science are caught in a spiral of diminishing returns and that quantity in some respects is outpacing quality. While unaddressed in the study, it also raises questions about the extent to which science can open new frontiers and sustain the kind of boldness that unlocked the atom and the universe and what can be done to address the shift away from pioneering discovery. Earlier studies have pointed to slowdowns in scientific progress but typically with less rigor.Mr. Park, along with Russell J. Funk, also of the University of Minnesota and Erin Leahey, a sociologist at the University of Arizona, based their study on an enhanced kind of citation analysis that Dr. Funk helped to devise. In general, citation analysis tracks how researchers cite one another’s published works as a way of separating bright ideas from unexceptional ones in a system flooded with papers. Their improved method widens the analytic scope.“It’s a very clever metric,” said Pierre Azoulay, a professor of technological innovation, entrepreneurship and strategic management at the Massachusetts Institute of Technology. “I was giddy when I saw it. It’s like a new toy.”Researchers have long sought objective ways to assess the state of science, which is seen as vital to economic growth, national pride and military strength. It became more difficult to do so as published papers soared in number to more than one million annually. Each day, that’s more than 3,000 papers — by any standard, an indecipherable blur.Defying the surge, experts have debated the value of incremental strides versus “Eureka!” moments that change everything known about a field.The new study could deepen the debate. One surprise is that discoveries hailed popularly as groundbreaking are seen by the authors of the new study as often representing little more than routine science, and true leaps as sometimes missing altogether from the conversation.For instance, the top breakthrough on the study’s list of examples is a gene-splicing advance that’s poorly known to popular science. It let foreign DNA be inserted into human and animal cells rather than just bacteria ones. The New York Times referred to it in a 1983 note of four paragraphs. Even so, the feat produced a run of awards for its authors and their institution, Columbia University, as well as almost $1 billion in licensing fees as it lifted biotechnology operations around the world.In contrast, the analysts would see two of this century’s most celebrated findings as representing triumphs of ordinary science rather than edgy leaps. The mRNA vaccines that successfully battle the coronavirus were rooted in decades of unglamorous toil, they noted.So too, the 2015 observation of gravitational waves — subtle ripples in the fabric of space-time — was no unforeseen breakthrough but rather the confirmation of a century-old theory that required decades of hard work, testing and sensor development.“Disruption is good,” said Dashun Wang, a scientist at Northwestern University who used the new analytic technique in a 2019 study. “You want novelty. But you also want everyday science.”The three analysts uncovered the trend toward incremental advance while using the enhanced form of citation analysis to scrutinize nearly 50 million papers and patents published from 1945 to 2010. They looked across four categories — the life sciences and biomedicine, the physical sciences, technology and the social sciences — and found a steady drop in what they called “disruptive” findings. “Our results,” they wrote, “suggest that slowing rates of disruption may reflect a fundamental shift in the nature of science and technology.”Their novel method — and citation analysis in general — get analytic power from the requirement that scientists cite studies that helped to shape their published findings. Starting in the 1950s, analysts began to tally those citations as a way to identify research of importance. It was a kind of scientific applause meter.But the count could be misleading. Some authors cited their own research quite often. And stars of science could receive lots of citations for unremarkable finds. Worst of all, some of the most highly cited papers turned out to involve minuscule improvements in popular techniques used widely by the scientific community.The new method looks at citations more deeply to separate everyday work from true breakthroughs more effectively. It tallies citations not only to the analyzed piece of research but to the previous studies it cites. It turns out that the previous work is cited far more often if the finding is routine rather than groundbreaking. The analytic method turns that difference into a new lens on the scientific enterprise.The measure is called the CD index after its scale, which goes from consolidating to disrupting the body of existing knowledge. Dr. Funk, who helped to devise the CD index, said the new study was so computationally intense that the team at times used supercomputers to crunch the millions of data sets. “It took a month or so,” he said. “This kind of thing wasn’t possible a decade ago. It’s just now coming within reach.”The novel technique has aided other investigators, such as Dr. Wang. In 2019, he and his colleagues reported that small teams are more innovative than large ones. The finding was timely because science teams over the decades have shifted in makeup to ever-larger groups of collaborators.In an interview, James A. Evans, a University of Chicago sociologist who was a co-author of that paper with Dr. Wang, called the new method elegant. “It came up with something important,” he said. Its application to science as a whole, he added, suggests not only a drop in the return on investment but a growing need for policy reform.“We have extremely ordered science,” Dr. Evans said. “We bet with confidence on where we invest our money. But we’re not betting on fundamentally new things that have the potential to be disruptive. This paper suggests we need a little less order and a bit more chaos.”

A new study published in the journal Cell Reports Medicine links exposure to salmonella bacteria to colon cancer risk.
The researchers, including a team led by Jun Sun from the University of Illinois Chicago, studied human colon cancer tissue samples and animal models and found that exposure to salmonella was linked with colon cancers that developed earlier and grew larger.
The study authors first looked at data from a Netherlands-based retrospective study of colon cancer patients that found tissue samples taken during routine colon cancer surgery with salmonella antibodies tended to be from people who had worse colon cancer outcomes.
Using salmonella strains isolated from these tissue samples, Sun and her U.S.-based team studied mice with colon cancer that had been exposed to the bacteria. They observed accelerated tumor growth and larger tumors in mice with salmonella exposure. They also saw that there was increased salmonella translocated to the tumors.
“During infection, salmonella hijacks essential host signaling pathways, and these molecular manipulations may cause oncogenic transformation. The current study tells us that more research is needed into the connection between salmonella exposure and colon cancer risk in the USA, and that simply by practicing safe food preparation, we can potentially help to protect ourselves,” said Sun, UIC professor of medicine.
Sun’s collaborators in the Netherlands also studied the bacteria in vitro. They combined human cancer cells and pre-cancer cells with the salmonella strain in the lab and measured any growth or changes in the tumor. They saw that even one infection caused transformation and that each salmonella infection exponentially increased the rate of cell transformation.
“The mouse and tissue culture experiments show that salmonella infection had a chronic effect to accelerate tumor growth,” said Sun, who also is a member of the University of Illinois Cancer Center at UIC. “This evidence tells us that we need to look closer at salmonella exposure as an environmental risk factor for chronic diseases, such as colon cancer.”
Leiden University Medical Center, the National Institute for Public Health and the Environment, and Utrecht University, all in the Netherlands, collaborated on this study.
In addition to Sun, co-authors of “Repetitive non-typhoidal Salmonella exposure is an environmental risk factor for colon cancer and tumor growth” include Daphne van Elsland, Janneke Duijster, Jilei Zhang, Virginie Stevenin, Yongguo Zhang, Lang Zha, Yinglin Xia, Eelco Franz, Lapo Mughini-Gras and Jacques Neefjes.

Researchers from Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, have found new evidence that vitamin D may be metabolized differently in people with an elevated body mass index (BMI). The study, appearing in JAMA Network Open, is a new analysis of data from the VITAL trial, a large nationwide clinical trial led by Brigham researchers that investigated whether taking vitamin D or marine omega-3 supplements could reduce the risk of developing cancer, heart disease, or stroke.
“The analysis of the original VITAL data found that vitamin D supplementation correlated with positive effects on several health outcomes, but only among people with a BMI under 25,” said first author Deirdre K. Tobias, ScD, an associate epidemiologist in Brigham’s Division of Preventive Medicine. “There seems to be something different happening with vitamin D metabolism at higher body weights, and this study may help explain diminished outcomes of supplementation for individuals with an elevated BMI.”
Vitamin D is an essential nutrient involved in many biological processes, most notably helping our body absorb minerals, such as calcium and magnesium. While some of the vitamin D we need is made in the body from sunlight, vitamin D deficiencies are often treated with supplementation. Evidence from laboratory studies, epidemiologic research and clinical research has also suggested that vitamin D may play a role in the incidence and progression of cancer and cardiovascular disease, and it was this evidence that prompted the original VITAL trial.
The VITAL trial was a randomized, double-blind, placebo-controlled trial in 25,871 U.S. participants, which included men over the age of 50 and women over the age of 55. All participants were free of cancer and cardiovascular disease at the time of enrollment. While the trial found little benefit of vitamin D supplementation for preventing cancer, heart attack, or stroke in the overall cohort, there was a statistical correlation between BMI and cancer incidence, cancer mortality, and autoimmune disease incidence. Other studies suggest similar results for type 2 diabetes.
The new study aimed to investigate this correlation. The researchers analyzed data from 16,515 participants from the original trial who provided blood samples at baseline (before randomization to vitamin D), as well as 2,742 with a follow-up blood sample taken after two years. The researchers measured the levels of total and free vitamin D, as well as many other novel biomarkers for vitamin D, such as its metabolites, calcium, and parathyroid hormone, which helps the body utilize vitamin D.
“Most studies like this focus on the total vitamin D blood level,” said senior author JoAnn E. Manson, MD, DrPH, chief of the Division of Preventive Medicine at the Brigham and principal investigator of VITAL. “The fact that we were able to look at this expanded profile of vitamin D metabolites and novel biomarkers gave us unique insights into vitamin D availability and activity, and whether vitamin D metabolism might be disrupted in some people but not in others.”
The researchers found that vitamin D supplementation increased most of the biomarkers associated with vitamin D metabolism in people, regardless of their weight. However, these increases were significantly smaller in people with elevated BMIs.
“We observed striking differences after two years, indicating a blunted response to vitamin D supplementation with higher BMI,” Tobias said. “This may have implications clinically and potentially explain some of the observed differences in the effectiveness of vitamin D supplementation by obesity status.”
“This study sheds light on why we’re seeing 30-40 percent reductions in cancer deaths, autoimmune diseases, and other outcomes with vitamin D supplementation among those with lower BMIs but minimal benefit in those with higher BMIs, suggesting it may be possible to achieve benefits across the population with more personalized dosing of vitamin D,” said Manson. “These nuances make it clear that there’s more to the vitamin D story.”
The authors conclude that the VITAL findings are a call to action for the research community to continue exploring the potential benefits of vitamin D supplementation for preventing cancer and other diseases and to take BMI into account when evaluating the supplement’s health impacts.
Disclosure: Co-author Julie Buring reported that her spouse was on the scientific advisory board of Pharmavite, which provided vitamin D and placebo.
Funding: The Vitamin D and Omega-3 Trial was supported by grant RO1ATO11729 from the National Center for Complementary and Integrative Health and, during the intervention phase, was supported by grants U01 CA138962 and R01 CA138962 from the National Cancer Institute; National Heart, Lung, and Blood Institute; Office of Dietary Supplements; National Institute of Neurological Disorders and Stroke; and the National Center for Complementary and Integrative Health. The ancillary studies are supported by grants from multiple institutes, including the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; the National Institute on Aging; the National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Institute of Mental Health; and others. Pharmavite LLC of Northridge, California (vitamin D) and Pronova BioPharma of Norway and BASF (Omacor fish oil) donated the study agents, matching placebos, and packaging in the form of calendar packs. Quest Diagnostics measured serum 25-hydroxyvitamin D, parathyroid hormone, and other biomarkers at no cost to the study. Dr LeBoff reported grants from National Institute of Arthritis and Musculoskeletal and Skin Diseases RO1 AR070854 and grants from National Institute of Arthritis and Musculoskeletal and Skin Diseases R01 ARO59775.

A simple nasal spray significantly reduced snoring and breathing difficulties in children and halved the number needing to have their tonsils removed, according to a new study.
The research, led by the Murdoch Children’s Research Institute and published in JAMA Pediatrics, found a saline (salt water) nasal spray was just as effective as an anti-inflammatory steroid nasal spray at easing sleep disordered breathing in children after six weeks of treatment.
The findings stated both nasal sprays cleared symptoms while asleep in about 40 per cent of cases and those assessed by a surgeon as needing their tonsils and/or adenoids removed was reduced by half. The randomised-controlled “MIST” trial of the sprays involved 276 children, aged 3-12 years, and was carried outat The Royal Children’s Hospital and Monash Children’s Hospital.
Tonsillectomy is the most common paediatric elective surgery for children in Australia with more than 40,000 performed each year. Commonly used to treat children’s snoring, the procedure is costly, painful and a significant burden on hospital resources.
Murdoch Children’s Dr Alice Baker said Victorian children typically waited more than a year in the public system for surgery to remove tonsils and adenoids, prompting a need to look for an alternative treatment for sleep disordered breathing. Some children may also be having their tonsils and adenoids out unnecessarily, she said.
“Nasal sprays work by cleaning the nose and/or reducing inflammation not just in the nose but all the way down the back of the throat to the adenoids and tonsillar tissue to alleviate the symptoms,” Dr Baker said.

Snoring and breathing difficulties during sleep affect about 12 per cent of children and can cause significant long-term issues impacting cognitive function, behaviour and cardiovascular health.
Murdoch Children’s Associate Professor Kirsten Perrett said the study found a substantial number of children with sleep disordered breathing could initially be managed by their GP and may not require referral to specialist services as currently recommended.
“A large proportion of children who snore and have breathing difficulties could be managed successfully by their primary care physician, using six weeks of an intranasal saline spray as a first-line treatment,” she said.
“Using this cheaper and readily available treatment would increase the quality of life of these children, reduce the burden on specialist services, decrease surgery waiting times and reduce hospital costs.”
Stephen Graham and Emily Tuner-Graham said their son, Thomas, 7, had stopped snoring and no longer needed his tonsils removed since taking part in the trial.
“From three years of age Thomas started snoring and we were concerned that he would eventually need surgery,” they said.
“Prior to joining the trial, a specialist recommended having his tonsils out. It’s a such huge relief that by just using a nasal spray his breathing difficulties have cleared.”
Researchers from the University of Melbourne, The Royal Children’s Hospital, Royal Hospital for Children in Glasgow, Monash Health and Monash University also contributed to the findings.

A new study conducted at the University of Turku, Finland, examined the association between the residential green environment and the individual oligosaccharide profile in the mother’s breastmilk. Oligosaccharides are sugar molecules that are the most common component in breastmilk after lactose and fat. So far, approximately 200 oligosaccharides have been discovered and they form a very versatile group of different kinds of complex structures.
The oligosaccharides in breastmilk can protect the infant from harmful microbes and reduce the risk of developing allergies and diseases. The oligosaccharides are also closely connected to the immune system and gut microbiota which also have an impact the infant’s health.
“Earlier studies have shown that genetic and biological factors, such as mother’s obesity, can change the oligosaccharide composition in breastmilk. Our aim was to study how green living environments affect the composition of oligosaccharides in breastmilk, as greener environments have been found to have a beneficial impact on immunity and reduce the risk of disease in children,” says Adjunct Professor Mirkka Lahdenperä from the Department of Biology at the University of Turku.
Closer connection to nature may affect child’s health via breastmilk
Approximately 800 mothers participated in the longitudinal follow-up study, the STEPS Study, that started at the University of Turku in 2007. The breastmilk samples were collected when the infants were three months old, after which the oligosaccharide composition was analysed at the Bode Lab at the University of California San Diego.
The residential green environments were measured at the time the child was born around the homes of the families with measures of greenness, diversity of vegetation, and naturalness index, i.e. how much human impact and intervention there has been in the residential area. The results were independent of the education level, occupation, marital status and health of the children’s parents as well as the socio-economic disadvantage in the residential area.
The study showed that the diversity of oligosaccharides increases and the composition of several individual oligosaccharides changes when the mother’s residential area includes more green environments.
“This could indicate that increased everyday contacts with nature could be beneficial for breastfeeding mothers and their children as the oligosaccharide composition of breastmilk would become more diverse. The results imply that breastfeeding could have a mediating role between residential green environments and health in infancy,” says Lahdenperä and continues:
“The results highlight the importance of understanding the biological pathways that can impact health and lead to the development of different diseases starting from infancy.”

Talk about a bright idea: Thanks to chemists at Rice University and Stanford University, lighting up the brain is no longer just a figure of speech.
Rice’s Han Xiao, Stanford’s Zhen Cheng and collaborators have developed a new tool for noninvasive brain imaging that can help illuminate hard-to-access structures and processes. Their small-molecule dye, or fluorophore, is the first of its kind that can cross the blood-brain barrier. What’s more, it allowed the researchers to differentiate between healthy brain tissue and a glioblastoma tumor in mice.
“This could be very useful for imaging-guided surgery, for example,” Xiao said. “Using this dye, a doctor could determine where the boundary is between normal brain tissue versus tumor tissue.”
The study is featured on the cover of the Dec. 28 issue of the Journal of the American Chemical Society.
If you’ve been to an aquarium or a nightclub, you’ve probably noticed the colorful glow that some objects or surfaces emit under a black light. Known as fluorescence, this glowing effect can be useful for rendering visible things that otherwise go unnoticed.
“Fluorescence imaging has been applied for imaging cancer in different parts of our body,” Xiao said. “The advantages of a fluorescence probe include high resolution and the ability to adapt the probe to read for different substances or activities.”
The deeper a tissue or organ is, the longer the wavelengths needed to discern the presence of fluorescent small molecules. For this reason, the second near-infrared (NIR-II) channel with wavelengths of 1,000 to 1,700 nanometers is especially important for deep-tissue imaging. For reference, visible light wavelengths range from 380 to 700 nanometers.

“Our tool is really valuable for deep imaging because it functions in the NIR-II region,” Xiao said. “In contrast to NIR-II wavelengths, fluorescent effects within the visible spectrum or with near-infrared wavelengths between 600 and 900 nanometers (NIR-I) will only get you skin-deep.”
Brain imaging poses a particular challenge not only because of tissue depth and accessibility, but also because of the blood-brain barrier, a layer of cells that acts as a very selective filter to restrict the passage of substances from the circulatory system to the central nervous system.
“People always want to know what exactly is happening in the brain, but it’s very hard to design a molecule that can penetrate the blood-brain barrier. Up to 98% of small-molecule drugs approved by the Food and Drug Administration (FDA) cannot,” Xiao said.
“Generally speaking, the reason a NIR-II dye molecule tends to be big is because it is a conjugated structure with many double bonds,” he continued. “This is a true problem and the reason why we have been unable to use fluorescence in brain imaging until now. We tried to address this issue by developing this new dye scaffold that is very small but has a long emission wavelength.”
Unlike the other two known NIR-II dye scaffolds, which are not capable of crossing the blood-brain barrier, the one developed by Xiao is more compact, which makes it a great candidate for probes or drugs targeting the brain. “In the future, we could modify this scaffold and use it to look for a lot of different metabolites in the brain,” Xiao said.
Beyond the brain, the dye developed by Xiao has much greater lasting power than indocyanine green, the only NIR small-molecule dye approved by the FDA for use as a contrast agent. A longer lifespan means researchers have more time to record the fluorescent trace before it disappears.
“When exposed to light, the indocyanine green dye trace deteriorates in seconds, whereas our dye leaves a stable trace for more than 10 minutes,” Xiao said.
The research was supported by the Cancer Prevention Research Institute of Texas (RR170014), the National Institutes for Health (GM133706, CA255894), the Department of Defense (W81XWH-21-1-0789), the Robert A. Welch Foundation (C-1970, C-0807), the National Science Foundation (1803066, 2203309), a Hamill Innovation Award, the John S. Dunn Foundation Collaborative Award and the Stanford University Department of Radiology.

Aging involves a balance between oxidants and antioxidants, low-grade inflammation and a protein response that occurs at the cellular level, which is responsible for many health disorders.
Exercise has been shown to regulate the inflammatory response, balance oxidants such as free radicals that build up in the cells and damage DNA; and ameliorate the process by which cells protect themselves against these stressors. Furthermore, resistance training in older adults is recommended to help maintain muscle, flexibility and balance.
Aging and related diseases are associated with alterations in oxidative status and low-grade inflammation, as well as a decreased endoplasmic reticulum (ER) unfolded protein response (UPR). UPR is a functional mechanism by which cells attempt to protect themselves against ER stress, resulting from the accumulation of the unfolded/misfolded proteins.
One group of proteins associated with the aging process is the mitochondrial heat shock protein 60 (HSP60), which has been demonstrated to play a protective role in the ability for cells to remain active and healthy. Currently, there is limited research investigating the effects of resistance training in older adults on the expression of HSP60 and Klotho, a gene involved in the aging process in mammals.
A new study by researchers at Florida Atlantic University, in collaboration with the University of León in Spain, examined whether an eight-week resistance training program would modulate the oxidative status, the UPR activation and key inflammatory pathways as well as their relationships with HSP60 and Klotho proteins.
For the study, researchers analyzed these proteins in peripheral blood mononuclear cells of elderly subjects. In addition, they utilized computer simulation to predict the key proteins associated with these biomolecules underlying physiological adaptations to exercise. They collected blood samples approximately five to six days before and after the training period and just before training intervention in young subjects who were included for basal assessments. Researchers also analyzed various oxidative stress biomarkers in peripheral blood mononuclear cells.
Results of the study, published in the journal Antioxidants, demonstrated that the levels of the inflammatory proteins (pIRAK1, TLR4, and TRAF6), as well as different markers of the redox balance (catalase, GSH, LP, NRF2, PC, ROS, SOD1, and SOD2) remained unchanged with training. Importantly, untrained elderly subjects showed a significant reduction in pIRE1/IRE1 ratio when compared to trained elderly subjects. Such a finding was further confirmed by a gene ontology analysis, showing that endoplasmic reticulum stress is a key mechanism modulated by IRE1. Additionally, analysis did not show the training effect on the expression of HSP60 and Klotho or their relationships with other outcome variables. Although elderly male and female subjects were included in the training program, researchers did not find any sex effects in the study. These findings might partially support the modulatory effect of resistance training on the endoplasmic reticulum in the elderly.
“Regular physical activity is suggested to be an effective intervention in improving age-related diseases such as osteoporosis, sarcopenia or muscle loss and dynapenia or loss of muscle strength, cardiovascular diseases, and type 2 diabetes,” said Chun-Jung “Phil” Huang, Ph.D., co-author and a professor in the Department of Exercise Science and Health Promotion within FAU’s Charles E. Schmidt College of Science. “Although the beneficial effects of regular physical exercise to alleviate inflammation and oxidative stress are well-established, the processes of these physiological adaptations with regard to protein folding or UPR remains to be explored. That is why we used a systems biology approach for our study.”
The resistance training protocol for the study consisted of 16 sessions over eight weeks (two sessions per week), with a minimum of 48 hours between sessions. The participants started with a 10-minute warm-up on a cycle ergometer. Subsequently, eight different resistance exercises (leg press, ankle extension, bench press, leg extension, bicep curl, pec deck, high pulley traction, and dumbbell lateral lift) were performed using the exercise device. For each exercise, participants performed three sets of 12-8-12 repetitions. There was a two-to-three-minute rest between each repetition and a three-minute rest between each exercise.
“We know how very important physical activity is for older adults and our study takes research one step further in helping to elucidate the benefits of exercise in this population,” said Huang.
Study co-authors are senior author Brisamar Estébanez, Ph.D.; Marta Rivera-Viloria; and José A. de Paz, M.D., all with the University of León; José E. Vargas, Ph.D., Universidad Federal do Paraná, Curtiba; and Nishant P. Visavadiay, Ph.D.; and Andy V. Kahmoui, Ph.D., both with FAU’s Department of Exercise Science and Health Promotion.

Artificial intelligence (AI) may help improve care for patients who show up at the hospital with acute chest pain, according to a study published in Radiology, a journal of the Radiological Society of North America (RSNA).
“To the best of our knowledge, our deep learning AI model is the first to utilize chest X-rays to identify individuals among acute chest pain patients who need immediate medical attention,” said the study’s lead author, Márton Kolossváry, M.D., Ph.D., radiology research fellow at Massachusetts General Hospital (MGH) in Boston.
Acute chest pain syndrome may consist of tightness, burning or other discomfort in the chest or a severe pain that spreads to your back, neck, shoulders, arms, or jaw. It may be accompanied by shortness of breath.
Acute chest pain syndrome accounts for over 7 million emergency department visits annually in the United States, making it one of the most common complaints.
Fewer than 8% of these patients are diagnosed with the three major cardiovascular causes of acute chest pain syndrome, which are acute coronary syndrome, pulmonary embolism or aortic dissection. However, the life-threatening nature of these conditions and low specificity of clinical tests, such as electrocardiograms and blood tests, lead to substantial use of cardiovascular and pulmonary diagnostic imaging, often yielding negative results. As emergency departments struggle with high patient numbers and shortage of hospital beds, effectively triaging patients at very low risk of these serious conditions is important.
Deep learning is an advanced type of artificial intelligence (AI) that can be trained to search X-ray images to find patterns associated with disease.

For the study, Dr. Kolossváry and colleagues developed an open-source deep learning model to identify patients with acute chest pain syndrome who were at risk for 30-day acute coronary syndrome, pulmonary embolism, aortic dissection or all-cause mortality, based on a chest X-ray.
The study used electronic health records of patients presenting with acute chest pain syndrome who had a chest X-ray and additional cardiovascular or pulmonary imaging and/or stress tests at MGH or Brigham and Women’s Hospital in Boston between January 2005 and December 2015. For the study, 5,750 patients (mean age 59, including 3,329 men) were evaluated.
The deep-learning model was trained on 23,005 patients from MGH to predict a 30-day composite endpoint of acute coronary syndrome, pulmonary embolism or aortic dissection and all-cause mortality based on chest X-ray images.
The deep-learning tool significantly improved prediction of these adverse outcomes beyond age, sex and conventional clinical markers, such as d-dimer blood tests. The model maintained its diagnostic accuracy across age, sex, ethnicity and race. Using a 99% sensitivity threshold, the model was able to defer additional testing in 14% of patients as compared to 2% when using a model only incorporating age, sex, and biomarker data.
“Analyzing the initial chest X-ray of these patients using our automated deep learning model, we were able to provide more accurate predictions regarding patient outcomes as compared to a model that uses age, sex, troponin or d-dimer information,” Dr. Kolossváry said. “Our results show that chest X-rays could be used to help triage chest pain patients in the emergency department.”
According to Dr. Kolossváry, in the future such an automated model could analyze chest X-rays in the background and help select those who would benefit most from immediate medical attention and may help identify patients who may be discharged safely from the emergency department.
“Deep Learning Analysis of Chest Radiographs to Triage Patients with Acute Chest Pain Syndrome.” Collaborating with Dr. Kolossváry were Vineet K. Raghu, Ph.D., John T. Nagurney, M.D., Udo Hoffmann, M.D., M.P.H., and Michael T. Lu, M.D., M.P.H.