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Patients who are most likely to suffer severe pain following an operation can be reliably identified using a new technique developed at the University of Birmingham.
The technique could allow clinicians to plan additional preventative pain medication during surgery for vulnerable patients. This could mean patients are likely to experience less acute pain during recovery, and are also less likely to go on to suffer chronic symptoms.
In a pilot study, published today (DATE) in the British Journal of Anaesthesia, a team of researchers showed how electroencephalography (EEG) can be used to measure brain activity in patients about to undergo chest surgery, or thoracotomy.
Before surgery, the team measured the patients’ alpha waves, brain signals which oscillate between 8 and 14 Hz. Then, over 72 hours following surgery, patients were asked to score their pain on a scale from 1-10. The researchers were able to demonstrate a clear link between the patient’s alpha waves and their responses to pain. In particular, they found that people whose alpha waves oscillated below 9 Hz were much more vulnerable to severe pain post-surgery.
Dr Ali Mazaheri, of the University of Birmingham’s Centre for Human Brain Health and School of Psychology, is senior author of the study. He said: “The experience of being in pain is complicated and subjective, but it’s clear that these alpha waves are a reliable indicator of how severely an individual will experience pain. That offers clinicians a really valuable biomarker that they can use to prevent pain becoming an issue, rather than treating it after it has taken hold and become a serious, and potentially chronic problem.”
The study was carried out by Samantha Millard, in the Centre for Human Brain Health, in collaboration with researchers in the University’s Institute of Inflammation and Ageing, University Hospitals Birmingham NHS Foundation Trust. It involved 16 patients about to undergo surgery to treat lung cancer.

Over the years, everyone loses a few brain cells. A study led by scientists from USC Stem Cell and the USC Neurorestoration Center presents evidence that adults can replenish at least some of what they’ve lost by generating new brain cells, and that this process is dramatically altered in patients with long-term epilepsy. The findings are published in Nature Neuroscience.
“Our study is the first to detail the presence of newborn neurons and an immature version of a related cell type, known as astroglia, in patients with epilepsy,” said Michael Bonaguidi, an assistant professor of stem cell biology and regenerative medicine, gerontology, and biomedical engineering at USC. “Our findings furnish surprising new insights into how immature astroglia might contribute to epilepsy — opening an unexplored avenue toward the development of new anti-seizure medications for millions of people.”
First author Aswathy Ammothumkandy, who is a postdoctoral fellow in the Bonaguidi Lab, and her colleagues collaborated with USC neurosurgeons Charles Liu and Jonathan Russin, who often treat patients with seizures that can’t be controlled with medication. Drug resistance is particularly common with mesial temporal lobe epilepsy, or MTLE, and affects one-third of all patients with this form of the disease. As a result, some patients need to undergo surgery to remove the section of the brain, the hippocampus, that causes their seizures.
“Many patients bravely and generously donate their surgical specimens for research to advance our understanding of epilepsy and to develop new and better therapies,” said Russin, an assistant professor of neurological surgery, and associate director of the USC Neurorestoration Center. “These patients know better than anyone the trade-offs involved in the current treatment options, which often either don’t provide adequate seizure control, or carry very serious cognitive side effects.”
The surgical specimens afforded a unique opportunity for the researchers to study living brain tissue from patients with epilepsy, and to compare its microscopic anatomy with post-mortem samples from people with no known neurological disease.
In the samples from people both with and without epilepsy, the scientists observed newborn neurons, adding compelling new evidence to the ongoing scientific debate about whether adults retain the ability to generate these cells. In the surgical specimens, the longer the patients had experienced seizures, the scarcer these newborn neurons became. More surprisingly, the surgical specimens contained a persistent population of immature astroglia that were not observed in the disease-free samples.
Because the brain tissue in the surgical specimens was still alive, the scientists could also use it to grow stem cells in the laboratory and test their ability to form newborn neurons and immature astrocytes. In these experiments, a longer disease duration reduced the ability to form newborn neurons and increased the production of immature astroglia, consistent with the team’s direct observations of the surgical specimens.
The team also studied electrical activity related to seizures. They found suspicious correlations between where electrical activity was localized within the surgical samples, and the location and behavior of the astroglia.
“Normally, astroglia are considered to be supporting cells, because their job is to create an environment where neurons can thrive,” said Ammothumkandy. “But in patients who have lived for many years with epilepsy, it might be immature astroglia that are contributing to both initiating and modulating chronic seizures.”
If this is the case, then immature astroglia could be an effective cell type to target by developing an entirely new class of anti-seizure medications.
“Currently available seizure medications tend to target neurons, so medications that act on immature astroglia could greatly expand the options for our patients,” said Liu, a professor of neurological surgery, neurology, and biomedical engineering, director of the USC Neurorestoration Center, and director of the USC Epilepsy Care Consortium. “A new class of drugs could combine with current medical and surgical strategies to control seizures without aggressive surgical removal of parts of the brain that can be critically important for learning, memory and emotional regulation.”
Bonaguidi, Liu and Russin originally kicked off the project with pilot funding from an Eli and Edythe Broad Innovation Award, which supports faculty pursuing research collaborations related to stem cells. The study brought together clinicians, scientists and engineers from across the Keck School of Medicine of USC — including at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, the USC Neurorestoration Center, and the Zilkha Neurogenetic — the USC Epilepsy Care Consortium, the USC Viterbi School of Engineering, and the USC Davis School of Gerontology, as well as other universities and medical centers.

Physically fit primary school pupils feel better and can concentrate better. They are more likely to make it to higher-level secondary grammar schools than children with less sporting abilities. This has been confirmed for the first time in a study by the Department of Sport and Health Sciences at the Technical University of Munich (TUM).
Movement on a regular basis keeps kids healthy and fit for school. The benefits of sports have been demonstrated in numerous studies. Now a research team at the TU Munich has found proof of the correlation between physical fitness, concentration and health-related quality of life for primary school pupils.
The study involved 3285 girls and 3248 boys from Bavaria’s Berchtesgadener Land district. The key criteria were physical strength and endurance, the ability to concentrate and health-related quality of life, as determined by the scientists according to internationally standardized test procedures.
Promoting children’s motor skills at an early stage is important
The results of the study show: The higher the level of children’s physical fitness, the better they can concentrate and the higher their health-related quality of life. While the boys did better on the fitness tests, the girls performed better in terms of concentration and quality of life values.
At the same time, in all tests for physical fitness overweight and obese children had significantly poorer results than underweight children and children with normal body weight. Obese children also had significantly poorer values for health-related quality of life on the whole, physical well-being, self-esteem as well as well-being in friendships and at school.

Scientists at St. Jude Children’s Research Hospital have evaluated how vaccination against, and infection with, SARS-CoV-2 affects the immune system. The results confirm that immunity by infection is not better than vaccination because both mount similar T-cell responses. In individuals who have already experienced COVID-19, getting vaccinated still expands T-cell memory and immune activation. A paper on the work appeared today in Nature Immunology.
Antigens are molecules that the immune system uses to recognize a threat such as an infection. Vaccinations and infections (in both the vaccinated and unvaccinated) expose the immune system to antigens. SARS-CoV-2 variants such as delta and omicron have added to the antigen landscape. Scientists studied how exposure to antigens before and after vaccination alters the immune response to the infection.
“If you’ve been infected, the vaccines still activate and expand your immune response in ways that can be protective,” said co-corresponding author Paul Thomas, Ph.D., St. Jude Department of Immunology. “If you’ve been vaccinated and then get infected, the vaccine still helps protect you. Very importantly, it doesn’t limit your ability to develop new immune responses to the strains that you’re infected with. The type of immunity on the T-cell side that the vaccine gives you look very similar to, and in some ways superior to, the response that you get from infection.”
The right tools to understand T cells
The study used data from the St. Jude?Tracking Study of Immune Responses Associated with COVID-19 (SJTRC). SJTRC started in 2020, enrolling St. Jude employees and monitoring their vaccination and immune response to the virus.
“This creative and comprehensive T cell work emphasizes the importance of the prospective study design that allowed us to collect samples from participants before they had COVID-19,” said co-corresponding author Joshua Wolf, Ph.D., M.B.B.S., St. Jude Department of Infectious Diseases. “A huge number of individuals at St. Jude gave their time and effort to make it possible.”
The researchers used specialized techniques to determine which small pieces of virus that T cells identify in different people. Single-cell sequencing of the RNA and T-cell receptors (scRNAseq and scTCRseq) provided a window into T-cell activity and which T-cell receptors were most important. The researchers also created tools, including monoclonal T-cell receptor cell lines, to examine immune responses. These cell lines help identify different parts of the virus.

Inspired by the advanced analytics used in sports, a Northwestern University-led research team has developed a new approach for measuring physician adherence to best practices. The study also shows that high-performing individuals are more likely to be aware of system-level challenges.
The data-driven method takes into consideration the characteristics of the patients seen by a physician (how sick a patient is, for example) in order to estimate an adjusted performance that more accurately captures the know-how of a set of physicians. The researchers’ case study focused on patients with acute respiratory distress syndrome (ARDS), a form of lung failure.
“Our new metric could help change behavior more broadly, beyond our case study, and increase adoption of medical innovations,” said Luís A. Nunes Amaral, a data science expert and a corresponding author of the study. “Our method also is very flexible — it can be used on individual physicians, on groups of physicians, on entire hospitals or on entire hospital groups.”
Amaral is the Erastus Otis Haven Professor of chemical and biological engineering at the McCormick School of Engineering. He also is co-director of NICO (Northwestern Institute on Complex Systems).
The study was published recently by the journal BMC Medical Research Methodology.
Dr. Curtis H. Weiss, a pulmonary and critical care physician at NorthShore University HealthSystem and an adjunct assistant professor at McCormick, also is a corresponding author of the study. Amaral has long collaborated with him, using data science to improve critical care medicine.

Patients who start abusing alcohol later in life — after age 40 — may be doing so secondary to an underlying neurologic condition, such as frontotemporal dementia, according to findings by a team of researchers from the Icahn School of Medicine at Mount Sinai and the University of California, San Francisco. The results are reported in the April 4 issue of the Journal of Alzheimer’s Disease.
Overall alcohol abuse — classified as when alcohol consumption negatively impacts work or social life or leads to legal ramifications — is present in 1.7 percent of older adults in the United States. Previous research has identified lifelong alcohol abuse as a risk factor for dementia. However, it has been unknown whether older adults who begin abusing acohol late in life have an underlying neurodegenerative disease. Particularly concerning is that people who begin abusing alcohol because of an underlying neurological condition may be misdiagnosed with primary alcohol abuse and referred to traditional addiction treatment programs, a process that may delay correct diagnosis and appropriate behavioral treatment, expend family resources, and add to patient and caregiver burden.
“Our study aimed to identify and compare the frequencies of lifetime alcohol abuse, late-onset alcohol abuse, and alcohol abuse as a first symptom of dementia in a group of patients living with several forms of dementia, including Alzheimer’s disease and frontotemporal dementia,” said Georges Nassan, MD, Associate Professor of Neurology, and Medical Director for the Division of Behavioral Neurology and Neuropsychiatry, at the Icahn School of Medicine at Mount Sinai and senior author of the paper. “What we found is that alcohol abuse may be the first sign of an underlying neurological condition when it presents late in life. In fact, up to 7 percent (nearly 1 in 15) of patients with frontotemporal dementia started abusing alcohol late in life, and 5 percent (1 in 20) did so as the first symptom of the disease. While it is important to identify social factors that may lead to alcohol abuse, such as retirement, loneliness, or loss of income/loved ones/housing, our data should implore health care workers to avoid systematically attributing alcohol abuse to these aspects and prompt clinicians to investigate the possibility of frontal lobe dysfunction.”
The research team conducted a cross-sectional, retrospective study of patients evaluated at an academic referral center between 1999 and 2017 who had a clinical diagnosis of behavioral variant frontotemporal dementia (bvFTD), Alzheimer’s-type dementia, or semantic variant primary progressive aphasia. The presence of alcohol abuse was screened using the National Alzheimer’s Coordinating Center UDS questionnaire completed by clinicians during patient research visits. Lifelong alcohol abuse was defined as alcohol abuse that began before the patient was 40 years old, late-onset alcohol abuse as abuse that began at age 40 or above, and alcohol abuse as a first symptom of dementia as abuse that started within the first three years, either before or after symptom onset.
Among the 1,518 participants screened, late-onset alcohol abuse affected 2.2 percent, higher than the 1.7 percent for older adults overall. The research team found that late-onset alcohol abuse was significantly more frequent in patients with bvFTD than those with Alzheimer’s-type dementia, while there was no difference between the frequency of lifelong alcohol abuse across the three dementia groups. They also found that alcohol abuse as a first symptom occurred in 1.4 percent of all patients, five times more frequently in patients with bvFTD than those with Alzheimer’s-type dementia. The results indicate not only that late-onset alcohol abuse is much more frequent in bvFTD than Alzheimer’s-type dementia, but also the likelihood that the biological mechanisms underlying late-onset and lifelong alcohol abuse are different.
“Because patients who begin using alcohol late in life are usually first seen by psychiatrists, primary care providers, and rehabilitation specialists, these professionals should be aware of the possibility that a neurodegenerative disease might be underlying the onset of alcohol abuse late in life in people who historically didn’t abuse alcohol. Therefore, a specific evaluation including checking for other frontal lobe symptoms should be performed, and patients at risk should be referred to a neurologist,” said Dr. Nassan. “An early and appropriate diagnosis in those patients is paramount for providing the best management, improving patients’ and families’ quality of life, and channeling patients to appropriate care facilities.”
Funding for this research was provided by the National Institutes of Health, The National Institute on Aging, and the Larry L. Hillblom Network Grant for the Prevention of Age-Associated Cognitive Declince.

The preclinical data for a vaccine developed at MedUni Vienna to protect against SARS-CoV-2 indicates that it is effective against all SARS-CoV-2 variants known to date, including omicron — even in those who have not yet built up any immunity as a result of vaccination (non-responders). The data from the study were recently published in the leading journal Allergy.
The antigen-based vaccine developed at MedUni Vienna, under the leadership of Rudolf Valenta from the Center for Pathophysiology, Infectiology and Immunology, targets the receptor binding domains (RBD) of the SARS-CoV-2 virus and induced a robust and uniform RBD-specific IgG antibody response in animal models and in human tests. This antibody response prevents the virus from docking onto and entering the body’s cells, so that infection cannot occur.
Combination of coronavirus vaccine and hepatitis B vaccine
The SARS-CoV-2 subunit vaccine (PreS-RBD) developed at MedUni Vienna is based on a structurally folded fusion protein consisting of two receptor binding domains (RBD) of the SARS-CoV-2 virus and the PreS antigen from hepatitis B, which serve as immunological carriers for each other, thereby strengthening the immune response. Currently available genetic SARS-CoV-2 vaccines induce mainly transient IgG1 antibody responses, whereas the PreS-RBD vaccine can additionally induce long-lived RBD-specific IgG4 antibodies.
PreS-RBD-specific IgG antibodies detected in blood and mucosal secretions reacted with SARS-CoV-2 variants, including the omicron variant. Antibodies induced by vaccination with PreS-RBD more potently inhibited the binding of RBD with its human receptor ACE2, and their virus-neutralizing titers were higher than those in a random sample of individuals fully immunized with two vaccinations of currently registered vaccines or than those of COVID-19 convalescents (i.e., individuals who had previously had COVID-19).
Immunity even for previous “non-responders”
“The PreS-RBD vaccine has the potential to induce sterilizing immunity to old and new SARS-CoV-2 variants by preventing infection by stopping viral replication and transmission through the inhibition of cellular virus entry,” explains study leader Rudolf Valenta. Moreover, it is expected that the vaccine will even be effective in people who have not previously responded to vaccination (“RBD non-responders”), as they will receive additional T-cell support from the PreS portion of the vaccine. An earlier study by Valenta and colleagues had found that approximately 20% of those recovered from COVID-19 failed to form RBD-specific antibodies and were thus at constant risk of re-infection.
Results based on decades of experience from allergy research at MedUni Vienna
The development of this Austrian COVID vaccine was to a large extent inspired by decades of experience in allergy vaccine design. Previous work on allergy vaccines and clinical trials also conducted with PreS-based allergy vaccines have demonstrated the safety of PreS-based vaccines, even when used repeatedly.
“Our data give us grounds to hope that this readily producible protein-based vaccine antigen will be effective against all SARS-CoV-2 variants known to date, including omicron,” says study leader Rudolf Valenta. “The vaccine is designed to enable repeated injections to build up sustained sterilizing immunity, is suitable for use in all age and risk groups and appears to be superior to currently available vaccines when it comes to inducing neutralizing antibodies.” If sufficient funding is forthcoming, the first clinical trials required for approval could be carried out this year.
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Materials provided by Medical University of Vienna. Note: Content may be edited for style and length.

New clinical research shows that lamivudine, a reverse transcriptase inhibitor widely used in HIV therapy, stopped disease progression in 25% of patients with fourth-line metastatic colorectal cancer. Findings from the trial, published in Cancer Discovery, raise the possibility of an unexpected promising direction in cancer treatment, not just colorectal cancer.
The trial included 32 patients with advanced metastatic colon cancer whose disease progressed despite four lines of previous cancer treatments. The first nine patients received the standard HIV-approved dose of lamivudine. “After giving them only this one drug — nothing else — we saw signs of disease stability,” says co-senior author David T. Ting, MD, of the Mass General Cancer Center. After adjusting the dosing four-fold, another 23 patients received lamivudine therapy where it was highly tolerated.
The research team observed that 9 of the 32 patients, or 28%, had disease stability or mixed response at the end of the trial. “This provides evidence that an HIV drug can be repurposed as an anti-cancer therapy in metastatic cancer patients,” says Ting. While the research team did not see tumor shrinkage, the results are encouraging.
“If we see this kind of response with just one HIV drug, the next obvious trial is to see what else we can achieve with HAART, or highly active anti-retroviral therapy,” adds Ting, referring to the standard three-drug regime for HIV treatment.
The first clues to this unusual drug trial surfaced in Ting’s lab and those of his collaborators over the past ten years. The team discovered that up to 50% of a tumor’s DNA was composed of “repetitive elements,” which were previously considered “junk DNA.” “Only cancer cells produced these repetitive element, not healthy cells,” says Ting. Colorectal cancers produce abundant amounts of repetitive elements, as do cancers of the esophagus, lung, and several others. These repetitive elements spew out extraordinary levels of RNA which replicate in a viral-like life cycle through reverse transcription into what Ting describes at the repeatome.
The repeatome acts much like a virus does relying on reverse transcription to replicate itself and move in the genome. “It’s a way for cancers to change their genome to adapt to stress,” adds Ting, who had the idea to assess whether an HIV drug, lamivudine, might interfere with the process.
In their preclinical studies, Ting found that colorectal cancer cells were sensitive to lamivudine, reducing their ability to move. The team also discovered that the drug induced DNA damage and interferon responses, an indication that the drug triggered an inflammatory response in the tumor cells. Although not proven or evaluated in this trial, Ting theorizes that pairing reverse transcriptase inhibitor therapy with immunotherapy might encourage immune cells to become involved in these cancers.
Research shows that in a U.S. population of HIV patients receiving three-drug anti-retroviral therapy for life, their incidence of colon, breast, and prostate cancer was significantly less than the general population. Ting speculates this kind of therapy might prevent a cancer or a recurrence or turn a crushing metastatic disease into a chronic disease like HIV.
“We did the trial to see if we could learn something new about the biology of cancer cells and in the process found this unexpected, very encouraging result,” says Ting. “Disease stability in a cancer patient population this advanced, with just one single agent, is highly unusual and we are hoping we can soon initiate a larger Phase III study with a three-drug reverse transcriptase inhibitor combination.”
This work was supported with grants from the National Institutes of Health, Gateway for Cancer Research, Stand Up To Cancer (SU2C), National Science Foundation, Burroughs Wellcome Fund, V Foundation for Cancer Research, Affymetrix, Inc., ACD-Biotechne, Robert L. Fine Cancer Research Foundation, and the Pershing Square Sohn Prize — Mark Foundation Fellowship.

Biomedical engineers at Duke University believe they have discovered the physical mechanism that causes high doses of antibiotics to promote the spread of antibiotic resistance between bacteria.
The culprit, they say, is an overabundance of “jumping genes,” called transposons, that carry the genetic instructions for resistance from the cell’s source code to plasmids that shuttle between cells.
The results appeared online March 28 in the journal Nature Ecology & Evolution.
“There’s a lot of evidence that suggests human pathogens likely pick up antibiotic resistance from other species living in the natural environment,” said Lingchong You, professor of biomedical engineering at Duke. “Intuitively, it makes sense that high levels of antibiotics in these environments are facilitating the jumping of resistance genes from chromosomes to plasmids so that they can spread, but the underlying mechanism never been directly tested. That’s where our work comes in.”
It’s no secret that the rise in antibiotic resistance in human pathogens has coincided with the rise in the use of antibiotics in large-scale industrial endeavors like farming and manufacturing. While the genes that provide resistance appear to be relatively new to these pathogens, some date back millions of years in bacteria living in certain wild ecosystems. Coupled with experiments that show high levels of antibiotics promote the spread of resistance both within and between bacterial species, it’s easy to draw the conclusion that human pathogens have acquired these resistance genes from the environment due to its increasing ambient levels of antibiotics.
While the cause and effect seems clear, research has never firmly established the underlying mechanisms, You said. Scientists know that small, free-floating bundles of DNA called plasmids carry resistance genes between cells. You’s own research, however, has shown that the presence of antibiotics does not increase the rate at which plasmids carry out these gene swaps. What then, the researchers asked, is the fundamental force driving this natural selection?

The foods we eat on a regular basis influence the makeup of the bacteria — both good and bad — in our mouths. And researchers are finding that this collective of bacteria known as the oral microbiome likely plays a large role in our overall health, in addition to its previously known associations with tooth decay and periodontal disease.
Scientists from the University at Buffalo have shown how eating certain types of foods impacts the oral microbiome of postmenopausal women. They found that higher intake of sugary and high glycemic load foods — like doughnuts and other baked goods, regular soft drinks, breads and non-fat yogurts — may influence poor oral health and, perhaps, systemic health outcomes in older women due to the influence these foods have on the oral microbiome.
In a study in Scientific Reports, an open access journal from the publishers of Nature, the UB-led team investigated whether carbohydrates and sucrose, or table sugar, were associated with the diversity and composition of oral bacteria in a sample of 1,204 postmenopausal women using data from the Women’s Health Initiative.
It is the first study to examine carbohydrate intake and the subgingival microbiome in a sample consisting exclusively of postmenopausal women. The study was unique in that the samples were taken from subgingival plaque, which occurs under the gums, rather than salivary bacteria.
“This is important because the oral bacteria involved in periodontal disease are primarily residing in the subgingival plaque,” said study first author Amy Millen, PhD, associate professor of epidemiology and environmental health in UB’s School of Public Health and Health Professions.
“Looking at measures of salivary bacteria might not tell us how oral bacteria relate to periodontal disease because we are not looking in the right environment within the mouth,” she added.
The research team reported positive associations between total carbohydrates, glycemic load and sucrose and Streptococcus mutans, a contributor to tooth decay and some types of cardiovascular disease, a finding that confirms previous observations. But they also observed associations between carbohydrates and the oral microbiome that are not as well established.
The researchers observed Leptotrichia spp., which has been associated with gingivitis, a common gum disease, in some studies, to be positively associated with sugar intake. The other bacteria they identified as associated with carbohydrate intake or glycemic load have not been previously appreciated as contributing to periodontal disease in the literature or in this cohort of women, according to Millen.
“We examined these bacteria in relation to usual carbohydrate consumption in postmenopausal women across a wide variety of carbohydrate types: total carbohydrate intake, fiber intake, disaccharide intake, to simple sugar intake,” Millen said. “No other study had examined the oral bacteria in relation to such a broad array of carbohydrate types in one cohort. We also looked at associations with glycemic load, which is not well studied in relation to the oral microbiome.”
The key question now is what this all means for overall health, and that’s not as easily understood just yet.
“As more studies are conducted looking at the oral microbiome using similar sequencing techniques and progression or development of periodontal disease over time, we might begin to make better inferences about how diet relates to the oral microbiome and periodontal disease,” Millen said.
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Materials provided by University at Buffalo. Original written by David Hill. Note: Content may be edited for style and length.