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The protection against infection from booster doses wanes quickly, in just a couple of months, so a booster shot now will not offer much defense in August or even July. It takes the immune system about a week to rev up after the shot. From that peak, antibodies taper down over the next two to three months. So if you qualify for a booster, you may want to have the maximum protection right before your trip — or before the next surge.“The one thing that matters is where we are in this whole pandemic,” Dr. Pepper said. “I would be watching what the variants are doing.”Late last year, when the Omicron variant was ubiquitous, getting a booster made sense simply to prevent infections. Dr. Wherry, who is 50, said he opted for a third dose even though he was not worried about becoming sick because getting infected would have been “extremely inconvenient” for his work and for his two children in high school.“Right now as a healthy 50-year-old, I don’t see any need for a fourth dose,” he said. But he might revisit that choice if the case numbers tick up again.

Scientists have shown how accelerated biological aging measured by an epigenetic clock may increase the risk of bowel cancer, according to a report published today in eLife.
The study provides evidence that biological age might play a causal role in the increased risk of certain diseases, and paves the way for interventions that could slow down this process.
Epigenetic markers are changes to DNA which may alter the way in which our genes work and are known to vary as we age. A type of epigenetic marker called DNA methylation is often used to measure age. DNA methylation patterns on the genome have been shown to relate closely with age and they can provide insights into ‘biological aging’ — that is, how old our cells look compared to how old they are in years.
“When an individual’s biological age is older than their chronological age, they are said to be experiencing epigenetic age acceleration,” explains first author Fernanda Morales-Berstein, a Wellcome Trust PhD Student in Molecular, Genetic and Lifecourse Epidemiology at the MRC Integrative Epidemiology Unit, University of Bristol, UK. “Epigenetic age acceleration, as measured by DNA methylation-based predictors of age called epigenetic clocks have been associated with several adverse health outcomes including cancer. But although epigenetics can be used to predict cancer risk or detect the disease early, it is still unclear whether accelerated epigenetic aging is a cause of cancer.”
Making a causal link between biological clocks and disease is challenging because it is hard to know whether biological aging increases the risk of disease, or whether other independent factors raise the risk of a disease and biological aging at the same time. To address this, the team used a method called Mendelian randomization to mimic a randomized trial evaluating the effectiveness of changes in epigenetic aging as a cancer prevention strategy. They used information on known genetic variants associated with levels of epigenetic age acceleration to investigate this.
The team compared four established epigenetic clocks used to measure biological aging and their genetically predicted associations with a range of cancer types. Two were first-generation clocks which use patterns of DNA methylation strongly linked to chronological age. The others were second-generation clocks which use markers associated with increased risk of age-related diseases or death.
They found limited evidence that accelerated epigenetic age is causally linked to breast, lung, ovarian or prostate cancer.
The most striking result was seen for bowel cancer, where the results measured by one of the second-generation clocks, called GrimAge, suggested a 12% increased risk of bowel cancer with every additional year of biological age (over chronological age). These results were further corroborated by an association between biological age acceleration and parental history of bowel cancer. Further analysis suggested that evidence for the risk was stronger for colon cancer compared with rectal cancer.
Previous studies have suggested that epigenetic age acceleration is influenced by several cancer risk factors, such as obesity and smoking. The additional evidence from the current study suggests that targeting this pathway, for example through lifestyle changes or epigenetic-targeted therapies, could help reduce this risk.
“Our work provides potentially relevant findings for public health,” says senior author Rebecca Richmond, Vice-Chancellor’s Research Fellow in Molecular Epidemiology at the MRC Integrative Epidemiology Unit, University of Bristol. “If epigenetic age acceleration is a causal mediator between risk factors and bowel cancer, the clock may be a treatable intermediary for when targeting the underlying risk factors is not feasible or too difficult to accomplish, particularly in populations at high risk. More research is needed to support our findings and evaluate whether epigenetic age acceleration can be modified by lifestyle or clinical interventions.”
This research was funded by: Wellcome; Cancer Research UK; Medical Research Council; Operational Programme ‘Competitiveness, Entrepreneurship and Innovation’; National Institute for Health Research (NIHR); NIHR Biomedical Research Centres; University Hospitals Bristol and Weston NHS Foundation Trust; Alzheimer’s Society; and National Institutes of Health.
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Materials provided by eLife. Note: Content may be edited for style and length.

A COVID-19 sensor developed at Johns Hopkins University could revolutionize virus testing by adding accuracy and speed to a process that frustrated many during the pandemic.
In a new study published today in Nano Letters, the researchers describe the new sensor, which requires no sample preparation and minimal operator expertise, offering a strong advantage over existing testing methods, especially for population-wide testing.
“The technique is as simple as putting a drop of saliva on our device and getting a negative or a positive result,” said Ishan Barman, an associate professor of mechanical engineering, who along with David Gracias, a professor of chemical and biomolecular engineering, are senior authors of the study. “The key novelty is that this is a label-free technique, which means no additional chemical modifications like molecular labeling or antibody functionalization are required. This means the sensor could eventually be used in wearable devices.”
Barman says the new technology, which is not yet available on the market, addresses the limitations of the two most widely used types of COVID-19 tests: PCR and rapid tests.
PCR tests are highly accurate, but require complicated sample preparation, with results taking hours or even days to process in a laboratory. On the other hand, rapid tests, which look for the existence of antigens, are less successful at detecting early infections and asymptomatic cases, and can lead to erroneous results.
The sensor is nearly as sensitive as a PCR test and as convenient as a rapid antigen test. During initial testing, the sensor demonstrated 92% accuracy at detecting SARS-COV-2 in saliva samples — comparable to that of PCR tests. The sensor was also highly successful at rapidly determining the presence of other viruses, including H1N1 and Zika.

Researchers at Lund University have discovered increased levels of of a microRNA in type 2 diabetes, which has a negative effect on insulin secretion. Their experiments on human insulin producing cells in the pancreas also demonstrates that it is possible to increase the insulin secretion by reducing the levels of this microRNA. An important goal of the research is to develop new treatments for people with the disease.
In type 2 diabetes, the ability of the pancreas to produce and release insulin is impaired. Previous studies have demonstrated that microRNAs are involved in this deterioration process. MicroRNAs are non-coding RNAs that regulate the number of genes and proteins in a cell. Reducing the amount of microRNA could be a possible treatment for patient with type 2 diabetes.
Research has shown that a certain microRNA, called miR-200c, seems to affect the insulin secretion in diabetic mice. Until now, there has been a lack of knowledge about the role of miR-200c when it comes to the insulin secretion in humans.
“Our study demonstrates that the levels of miR-200c differs between people with and without the disease. Few studies within this area have been conducted with a similar amount of human material as in this study,” says Lena Eliasson, a diabetes researcher at Lund University Diabetes Centre (LUDC) and corresponding author for the study, published in the scientific journal Diabetes.
Increased insulin secretion
Their measurements of miR-200c in islets of Langerhans from 34 deceased donors with and without type 2 diabetes demonstrated increased levels of miR-200c in people with the disease. The researchers also carried out experiments in islets of Langerhans from deceased donors with type 2 diabetes in order to determine whether it is possible to increase the insulin secretion by reducing the levels of miR-200c in the cells. The experiments resulted in an increased insulin secretion in the islets of Langerhans of the three donors.

A study in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP), published by Elsevier, reports that, among youth with substance use and depression, a significant proportion show early improvements in depression during their treatment for substance use. Youth who are using cannabis less frequently prior to treatment and those without conduct disorder are more likely to experience early depression improvement.
“The combination of alcohol or cannabis use and depression is a significant problem in adolescents and young adults. In addition to the negative outcomes associated with substance use, like automobile accidents and academic problems, those with both conditions tend to have longer episodes of depression, more substance-related problems, and, most importantly, an increased risk for suicidal behavior,” said lead author John Curry, PhD, Professor Emeritus in the Department of Psychiatry & Behavioral Sciences at Duke University, Durham, NC. “Yet there is no standard approach to treating them, and they are often treated in two separate systems of care.”
Earlier studies have shown that some of these young people will show significant improvement in depression during treatment for substance use alone, suggesting that if that improvement is sustained, they may not need additional depression treatment. Based on this evidence, the researchers tested an adaptive approach in which everyone received substance use treatment. Yet, if they were still depressed after a month, they would receive additional depression treatment either with the same therapist or in the community.
“This approach allowed us to examine two different approaches to depression treatment for youth with substance use,” said Dr. Curry. “We also wanted to discover what proportion of the youth would have an early depression response during substance use treatment and what factors predicted it.”
Across two sites, a sample of 95 youths between the ages of 14 and 21 with alcohol or cannabis use and depressive symptoms received up to 12 sessions of cognitive behavior therapy (CBT) for substance use over 14 weeks. Before treatment, they completed measures of psychiatric diagnoses, alcohol or cannabis use, and severity of depression. Early depression response was defined as a 50% reduction in symptoms by week 4 of treatment. Those without early depression response were randomized to add either CBT for depression with the same therapist or depression treatment in the community.
Thirty-five participants (37%) demonstrated early depression response. Predictors of early depression response were lower frequency of cannabis use at baseline and lack of a conduct disorder diagnosis. No other variables — including demographic characteristics, severity of depression, or other psychiatric diagnoses — were predictors. Frequency of drinking, heavy drinking, and cannabis use declined over the full course of treatment for all participants. Among those without early depression response, depression improved significantly with either additional CBT or community treatment, with no difference between treatments.
“This treatment study emphasizes the importance of recognizing the heterogeneity of youth with substance use and co-occurring disorders such as depression, including the different trajectories of their responses to treatment,” said lead author Yifrah Kaminer, MD, MBA, Professor Emeritus of Psychiatry at the University of Connecticut, Storrs, CT. “An important finding is that the level of cannabis use affects the trajectory of change in depression during treatment. Additional examination of potential biological markers or other predictors of treatment response is of paramount importance for developing cost-effective interventions.”
Additional analyses will examine the course of depression and substance use after treatment, and whether the young people whose depression responded to substance use treatment continue to remain less depressed. Given the relatively small sample, it will be important to replicate the study’s findings in other samples. Future research is needed to investigate the factors that underlie the relationship between substance use and depression over time.
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Materials provided by Elsevier. Note: Content may be edited for style and length.

Researchers at the University of Toronto have created a genome editing technology that allows for slight variations in target DNA but retains local specificity, and which could help realize the potential of CRISPR/Cas-based gene therapy and pathogen diagnosis.
Scientists program current CRISPR/Cas systems to recognize and cut precise DNA sequences, to avoid effects such as snipping the wrong sequence or encouraging unwanted mutations. But that specificity makes it hard for the systems to identify common variants of a given DNA sequence, which has partly limited their application.
“A lot of work has gone into making CRISPR/Cas systems more specific,” said Basil Hubbard, principal investigator on the research who is an associate professor of pharmacology and toxicology in U of T’s Temerty Faculty of Medicine. “But for certain applications there is also the need for more flexible targeting in these systems, and our study shows a possible way to meet that need.”
The journal Nature Communications published the findings recently.
CRISPR-Cas systems contain two main molecules: a CRISPR guide-RNA, which contains nucleotide base pairs (adenine, cytosine, guanine and thymine in various combinations) that guide the system to a complementary stretch of DNA; and a Cas enzyme that cuts the DNA to allow for manipulation of other genetic code.
The new approach substitutes universal bases for one or more of the four bases that make up CRISPR guide-RNAs.

A new approach from Penn Medicine researchers could cut the time it takes to alter patients’ immune cells for infusion back into the body to find and attack cancer. The cell manufacturing process for this type of immunotherapy that was pioneered at Penn — CAR T cell therapy — typically takes nine to 14 days. In a pre-clinical study published in Nature Biomedical Engineering, a team in the Perelman School of Medicine at the University of Pennsylvania abbreviated this process and generated functional CAR T cells with enhanced anti-tumor potency in just 24 hours.
These results demonstrate the potential for a vast reduction in the time, materials, and labor required to generate CAR T cells, which could be especially beneficial in patients with rapidly progressive disease and in resource-poor healthcare environments. The study was led by Center for Cellular Immunotherapies researchers Michael C. Milone, MD, PhD, anassociate professor of Pathology and Laboratory Medicine and Saba Ghassemi, PhD, a research assistant professor of Pathology and Laboratory Medicine.
“While traditional manufacturing approaches used to create CAR T cells that take several days to weeks continue to work for patients with ‘liquid’ cancers such as leukemia, there is still a significant need to reduce the time and cost of producing these complex therapies” Milone said. “Building on our research from 2018 that reduced the standard manufacturing approach to three days, and now to less than 24 hours, the manufacturing method reported in this study is a testament to the potential to innovate and improve the production of CAR T cell therapies for the benefit of more patients.”
CAR T cell therapy is a type of immunotherapy used to fight cancer with a patient’s own altered immune cells. T cells are taken from a patient’s blood and changed in the lab by adding a gene for a receptor (called a chimeric antigen receptor or CAR). The CAR T cells are then infused back into a patient to find, bind to, and destroy cancer cells. However, when removed too long from the body during the engineering process, T cells can lose their ability to replicate, which is central to their effectiveness as a living drug. Thus, the Penn research team sought to shorten the process without sacrificing the T cell potency.
In animal models, the researchers learned that the quality, rather than the quantity, of the CAR T cell product is an important determinant of their efficacy. Their experiment provided evidence that a smaller number of high-quality CAR T cells that are generated without extensive expansion outside the body is superior to a higher number of reduced-quality CAR T cells that are extensively expanded before returning to the patient.
Traditional manufacturing approaches require T cells to be stimulated (or “activated”) in a way that induces the cells to replicate and expand in number. A key to the Penn researchers’ manufacturing approach is the lentiviral vector that delivers the CAR gene to the T cells. Lentiviral vectors, which are derived from the human immunodeficiency virus (HIV), are able to transfer genes like the CAR to cells without the need for this initial “activation” step, but the efficiency of this process was low. Using engineering approaches that built in part upon knowledge of how HIV naturally infects T cells, the Penn researchers developed a way to overcome this requirement for T cell activation and deliver genes directly to non-activated T cells freshly isolated from the blood. This had a dual benefit of expediting the overall manufacturing process while also maintaining T cell potency. Patients are not being infected with HIV through this process.
The process of engineering T cells is costly and time-intensive, since the treatment must be manufactured for each individual patient. The team hopes that cutting manufacturing time could make the therapy more cost-effective and accessible to more patients.
“This innovative approach is remarkable in that it may be able to help patients who might otherwise not be able to benefit from CAR T cell therapy such as those with rapidly progressing cancer due to significant time currently need to generate these therapies,” Ghassemi said. “Efficient reprogramming of T cells with a CAR in as little as 24 hours in a more simplified manufacturing process without T cell activation or extensive culture outside the body also offers the possibility of expanding where and when these therapies are produced. Not only might it improve the production capacity of centralized manufacturing facilities, but if simple and consistent enough, it might be possible to produce these therapies locally near the patient, which could be tantamount to addressing the many logistical challenges that impede delivery of this effective therapy especially in resource-poor environments.”
This study is a catalyst for more clinical research to investigate how the engineered CAR T cells, through this shortened approach, work in patients with specific cancers.
Penn scientists led research, development and clinical trials of this pioneering CAR T therapy in collaboration with Novartis and Children’s Hospital of Philadelphia. In 2017, the experimental therapy now known as Kymriah®, became the first CAR T cell approved by the U.S. Food and Drug Administration (FDA), for the treatment of pediatric and young adult patients with acute lymphoblastic leukemia (ALL). The therapy was also approved for certain types of lymphoma in 2018.
The study originated in work supported by the Novartis Institutes for BioMedical Research through a research alliance with the University of Pennsylvania. It was funded by a St. Baldrick’s Foundation Scholar Award, a National Blood Foundation Scientific Research Grant Award, and the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Cancer Research Program (W81XWH-20-1-0417) and RO1CA226983.

A new study shows that a potential treatment for Alzheimer’s disease may also improve cognitive function in people with Down syndrome.
The drug sargramostim (GM-CSF, which stands for granulocyte-macrophage colony-stimulating factor) is the first to show memory improvement in Alzheimer’s patients in a phase II clinical trial. GM-CSF is a normal human protein that is safe and well-tolerated with over 30 years of FDA-approved use for other disorders.
A multidisciplinary team at the University of Colorado Anschutz Medical Campus studied the safety and tolerability of GM-CSF treatment and its effects on behavior and brain pathology in a mouse model of Down syndrome and in mice undergoing typical aging. The results reported in the journal Neurobiology of Disease suggest that GM-CSF has potential applicability to humans.
“People with Down syndrome are at higher risk for Alzheimer’s disease and previous work showed that GM-CSF improves cognition and brain pathology in Alzheimer’s disease patients. This new study shows that GM-CSF also, unexpectedly, improves cognition in mice that do not have Alzheimer’s disease,” said senior author Huntington Potter, PhD, professor of neurology at the University of Colorado School of Medicine, director of the University of Colorado Alzheimer’s and Cognition Center and director of Alzheimer’s disease research at the Linda Crnic Institute for Down Syndrome. All three groups are located on the CU Anschutz Medical Campus.
He adds, “Discovering a treatment that may help children and young adults with Down syndrome to develop their physical and mental capabilities is critical to improving their health and activities of daily living.”
The research team, led by Md. Mahiuddin Ahmed, PhD, discovered that treatment with GM-CSF, which has pro-inflammatory, anti-inflammatory and immune regulatory properties, reverses learning and memory deficits, the loss of certain nerve cells, and other abnormalities in the brain in a mouse model of Down syndrome and also improves cognition in normal aging mice. The human version of GM-CSF/sargramostim has already been shown to be effective in improving cognition in people with mild-to-moderate Alzheimer’s disease and in cancer patients. The findings support the hypothesis that GM-CSF/sargramostim may promote neuronal recovery from injury or from neurological disease through multiple mechanisms, some of which evidently enhance cognitive function.
The next step is to determine whether this treatment is safe, tolerable and efficacious in people with Down syndrome.
The CU Anschutz Medical Campus team was recently awarded a grant from the National Institutes of Health/National Institute on Aging to study sargramostim treatment in young adults with Down syndrome who do not show evidence of Alzheimer’s disease. They will investigate its safety and potential efficacy regarding cognitive function, quality of life measures and biomarkers associated with neuronal damage.
“We are breaking new ground in studying sargramostim for multiple, different disorders — Down syndrome and Alzheimer’s disease,” Potter said. “We hope that this therapy, already proven to be safe for other diseases, will greatly improve cognitive function in people with Down syndrome.”
The new NIH-funded project, co-directed by Potter and Peter Pressman, MD, from the CU department of neurology, will leverage collaborations between research teams on the CU Anschutz Medical Campus and at Colorado State University. They will work closely with the Linda Crnic Institute for Down Syndrome, which is an affiliate of the Global Down Syndrome Foundation (GLOBAL). GLOBAL is the leading Down syndrome organization successfully advocating for Down syndrome research funding at the NIH.
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Materials provided by University of Colorado Anschutz Medical Campus. Original written by Julia Milzer. Note: Content may be edited for style and length.

Some people recovering from COVID-19 pneumonia have CT evidence of damage to their lungs that persists a full year after the onset of symptoms, according to a new study published in the journal Radiology.
The COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has considerably increased the demand for acute and post-acute healthcare worldwide.
COVID-19’s short-term effects on the lungs, such as pneumonia, are well documented. Much less is known about the illness’ long-term effects on the lungs.
As part of an Austria-based observational study on the development of lung disease in patients with SARS-CoV-2 infection, researchers looked at patterns and rates of improvement of chest CT abnormalities in patients one year after COVID-19 pneumonia. CT has been an important imaging tool in the workup of patients suspected of having COVID-19.
The researchers assessed lung abnormalities on chest CT in 91 participants, mean age 59 years, at several points over one year after the onset of COVID-19 symptoms.
At one year, CT abnormalities were present in 49, or 54%, of the 91 participants. Of these 49 participants, two (4%) had received outpatient treatment only, while 25 (51%) were treated on a general hospital ward and 22 (45%) had received intensive care unit (ICU) treatment.

Artificial intelligence (AI) is an effective tool for fracture detection that has potential to aid clinicians in busy emergency departments, according to a study in Radiology.
Missed or delayed diagnosis of fractures on X-ray is a common error with potentially serious implications for the patient. Lack of timely access to expert opinion as the growth in imaging volumes continues to outpace radiologist recruitment only makes the problem worse.
AI may help address this problem by acting as an aid to radiologists, helping to speed and improve fracture diagnosis.
To learn more about the technology’s potential in the fracture setting, a team of researchers in England reviewed 42 existing studies comparing the diagnostic performance in fracture detection between AI and clinicians. Of the 42 studies, 37 used X-ray to identify fractures, and five used CT.
The researchers found no statistically significant differences between clinician and AI performance. AI’s sensitivity for detecting fractures was 91-92%.
“We found that AI performed with a high degree of accuracy, comparable to clinician performance,” said study lead author Rachel Kuo, M.B. B.Chir., from the Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences in Oxford, England. “Importantly, we found this to be the case when AI was validated using independent external datasets, suggesting that the results may be generalizable to the wider population.”
The study results point to several promising educational and clinical applications for AI in fracture detection, Dr. Kuo said. It could reduce the rate of early misdiagnosis in challenging circumstances in the emergency setting, including cases where patients may sustain multiple fractures. It has potential as an educational tool for junior clinicians.
“It could also be helpful as a ‘second reader,’ providing clinicians with either reassurance that they have made the correct diagnosis or prompting them to take another look at the imaging before treating patients,” Dr. Kuo said.
Dr. Kuo cautioned that research into fracture detection by AI remains in a very early, pre-clinical stage. Only a minority of the studies that she and her colleagues looked at evaluated the performance of clinicians with AI assistance, and there was only one example where an AI was evaluated in a prospective study in a clinical environment.
“It remains important for clinicians to continue to exercise their own judgment,” Dr. Kuo said. “AI is not infallible and is subject to bias and error.”
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Materials provided by Radiological Society of North America. Note: Content may be edited for style and length.