Patients with type 2 diabetes that were treated with a weekly injection of the breakthrough drug Semaglutide were able to achieve an average weight loss of nearly 10kg, according to a new study published in The Lancet today.
Led by Melanie Davies, Professor of Diabetes Medicine at the University of Leicester and the Co-Director of the Leicester Diabetes Centre, the study showed that two thirds of patients with type 2 diabetes that were treated with weekly injections of a 2.4mg dose of Semaglutide were able to lose at least 5% of their body weight and achieved significant improvement in blood glucose control.
More than a quarter of patients were able to lose more than 15% of their body weight — far above that which has been observed with any other medicine administered to people with diabetes.
Professor Melanie Davies said: “These results are exciting and represent a new era in weight management in people with type 2 diabetes — they mark a real paradigm shift in our ability to treat obesity, the results bring us closer to what we see with more invasive surgery.
“It is also really encouraging that along with the weight loss we saw real improvements in general health, with significant improvement in physical functioning scores, blood pressure and blood glucose control.”
This global multi-centre trial was conducted at 149 sites in 12 countries across North America, Europe, South America, the Middle East, South Africa and Asia, involving 1,210 patients with type 2 diabetes whose current treatment was not achieving sufficient blood sugar control, for instance through diet and exercise, or through the use of metformin and other glucose lowering medicines used to control the disease.
It is one of a portfolio of studies conducted as part of the Semaglutide Treatment Effect for people with obesity Programme (STEP) programme. Professor Davies has been involved in all four of the STEP clinical trials involving Semaglutide for weight management completed so far, where the medication was shown to help patients achieve an average weight of loss of between 10kg and 17kg of body weight.
Being overweight or obese is a significant contributor to type 2 diabetes. Many patients can manage their type 2 diabetes by eating a healthy diet, taking regular exercise, and using medications to help control blood sugar, or achieve glycemic control but for a significant minority of patients who have not seen much improvement in spite of these methods, semiglutide is a promising development.
This study was also supported by the NIHR Leicester Biomedical Research Centre, of which Professor Davies is the Director.

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Imagine you’re driving up a hill toward a traffic light. The light is still green so you’re tempted to accelerate to make it through the intersection before the light changes. Then, a device in your car receives a signal from the controller mounted on the intersection alerting you that the light will change in two seconds — clearly not enough time to beat the light. You take your foot off the gas pedal and decelerate, saving on fuel. You feel safer, too, knowing you didn’t run a red light and potentially cause a collision in the intersection.
Connected and automated vehicles, which can interact vehicle to vehicle (V2V) and between vehicles and roadway infrastructure like traffic signals and stop signs (V2I), promise to save energy and improve safety. In a new study published in Transportation Research Part B, engineers from Michigan Technological University propose a modeling framework for V2V and V2I cooperative driving.
Cooperative driving helps cars and their drivers safely and efficiently navigate. The framework uses an eco-driving algorithm that prioritizes saving fuel and reducing emissions. The automated algorithm calculates location-based traffic control devices and roadway constraints using maps and geographic information. The research is led by Kuilin Zhang, associate professor of civil and environmental engineering and affiliated associate professor of computer science at Michigan Tech, along with Shuaidong Zhao ’18, now a senior quantitative analyst at National Grid.
For the past three years, Houghton, Michigan, has been home to roadside units installed on five of the city’s traffic signals that make V2I communication possible. Zhang conducted a simulation analysis using real traffic signal phasing and timing messages from the Ann Arbor connected vehicle test environment and plans to expand testing in the Houghton area.
“The whole idea of cooperative driving automation is that the signals in the intersection tell your car what’s happening ahead,” Zhang said. “The sensor at the intersection can benefit all connected vehicles passing through the intersection. The automated eco-driving algorithm improves the driving decisions of the connected and automated vehicles.”
The simulation results show that the cooperative automated eco-driving algorithm saves energy — 7% under light traffic and 23% under heavy traffic along the corridor.
“The stop and go, stop and go, it may use a lot of energy,” Zhang said. “The concept of eco-driving incorporates how the vehicle makes driving decisions using data not only from vehicles in front of it, but also with information given from a traffic signal.”
Zhang’s model pulls in high-definition (HD) maps, which use a connected vehicle’s hardware and software to provide down-to-the-centimeter accuracy in navigation. HD maps incorporate multiple types of environmental sensing: long-range radar, lidar, camera footage, short/medium-range radar and ultrasound.
Zhang said for autonomous driving, it’s important to know landmarks to control the car’s driving, as well as hill grades; using a hill to slow or accelerate a car can also increase energy savings. It’s easy to conserve energy on a straight highway; on busy arterial streets with traffic and stoplights, energy conservation isn’t so simple. On city streets, Zhang and Zhao’s online predictive connected and automated eco-driving model considers traffic control devices and road geometry constraints under light and heavy traffic conditions.

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Materials provided by Michigan Technological University. Original written by Kelley Christensen. Note: Content may be edited for style and length.

In the 1995 movie “Outbreak,” Dustin Hoffman’s character realizes, with appropriately dramatic horror, that an infectious virus is “airborne” because it’s found to be spreading through hospital vents.
The issue of whether our real-life pandemic virus, SARS-CoV-2, is “airborne” is predictably more complex. The current body of evidence suggests that COVID-19 primarily spreads through respiratory droplets — the small, liquid particles you sneeze or cough, that travel some distance, and fall to the floor. But consensus is mounting that, under the right circumstances, smaller floating particles called aerosols can carry the virus over longer distances and remain suspended in air for longer periods. Scientists are still determining SARS-CoV-2’s favorite way to travel.
That the science was lacking on how COVID-19 spreads seemed apparent a year ago to Tami Bond, professor in the Department of Mechanical Engineering and Walter Scott, Jr. Presidential Chair in Energy, Environment and Health. As an engineering researcher, Bond spends time thinking about the movement and dispersion of aerosols, a blanket term for particles light and small enough to float through air – whether cigarette smoke, sea spray, or hair spray.
“It quickly became clear there was some airborne component of transmission,” Bond said. “A virus is an aerosol. Health-wise, they are different than other aerosols like pollution, but physically, they are not. They float in the air, and their movement depends on their size.”
The rush for scientific understanding of the novel coronavirus has focused — understandably — on biological mechanisms: how people get infected, the response of the human body, and the fastest path to a vaccine. As an aerosol scientist, Bond went a different route, convening a team at Colorado State University that would treat the virus like any other aerosol. This team, now published in Environmental Science and Technology, set out to quantify the dynamics of how aerosols like viruses travel from one person to another, under different circumstances.
The cross-section of expertise to answer this question existed in droves at CSU, Bond found. The team she assembled includes epidemiologists, aerosol scientists, and atmospheric chemists, and together they created a new tool for defining how infectious pathogens, including SARS-CoV-2, transport in the air.

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Effectively rebreathed air
Their tool is a metric they’re calling Effective Rebreathed Volume, or simply, the amount of exhaled air from one person that, by the time it travels to the next person, contains the same number of particles. Treating virus-carrying particles agnostically like any other aerosol allowed the team to make objective, physics-based comparisons between different modes of transmission, accounting for how sizes of particles would affect the number of particles that traveled from one person to another.
They looked at three size categories of particles that cover a biologically relevant range: 1 micron, 10 microns, and 100 microns — about the width of a human hair. Larger droplets expelled by sneezing would be closer to the 100-micron region. Particles closer to the size of a single virion would be in the 1-micron region. Each have very different air-travel characteristics, and depending on the size of the particles, different mitigation measures would apply, from opening a window, to increasing fresh air delivery with through an HVAC system.
They compiled a set of models to compare different scenarios. For example, the team compared the effective rebreathed volume of someone standing outdoors 6 feet away, to how long it would take someone to rebreathe the same amount of air indoors but standing farther away.
Confinement matters
The team found that distancing indoors, even 6 feet apart, isn’t enough to limit potentially harmful exposures, because confinement indoors allows particle volumes to build up in the air. Such insights aren’t revelatory, in that most people avoid confinement in indoor spaces and generally feel safer outdoors. What the paper shows, though, is that the effect of confinement indoors and subsequent particle transport can be quantified, and it can be compared to other risks that people find acceptable, Bond said.

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Co-authors Jeff Pierce in atmospheric science and Jay Ham in soil and crop sciences helped the team understand atmospheric turbulence in ways that could be compared in indoor and outdoor environments.
Pierce said he sought to constrain how the virus-containing particles disperse as a function of distance from the emitting person. When the pandemic hit last year, the public had many questions about whether it was safe to run or bike on trails, Pierce said. The researchers found that longer-duration interactions outdoors at greater than 6-foot distances appeared safer than similar-duration indoor interactions, even if people were further apart indoors, due to particles filling the room rather than being carried away by wind.
“We started fairly early on in the pandemic, and we were all filled with questions about: ‘Which situations are safer than others?’ Our pooled expertise allowed us to find answers to this question, and I learned a lot about air filtration and air exchange in my home and in my CSU classroom,” Pierce said.
More to learn
What remains unclear is which size particles are most likely to cause COVID-19 infection.
Viruses can be carried on droplets large and small, but there is likely a “sweet spot” between droplet size; ability to disperse and remain airborne; and desiccation time, all of which factor into infective potential, explained Angela Bosco-Lauth, paper co-author and assistant professor in biomedical sciences.
The paper includes an analysis of the relative infection risk of different indoor and outdoor scenarios and mitigation measures, depending on the numbers of particles being inhaled.
“The problem we face is that we still don’t know what the infectious dose is for people,” Bosco-Lauth said. “Certainly, the more virus present, the higher the risk of infection, but we don’t have a good model to determine the dose for people. And quantifying infectious virus in the air is tremendously difficult.”
Follow-up pursuits
The team is now pursuing follow-up questions, like comparing different mitigation measures for reducing exposures to viruses indoors. Some of these inquiries fall into the category of “stuff you already know, but with numbers,” Bond said. “People are now thinking, OK, more ventilation is better, or remaining outside is better, but there is not a lot of quantification and numbers behind those recommendations,” Bond said.
Bond hopes the team’s work can lay a foundation for more up-front quantification of transmission dynamics in the unfortunate event of another pandemic. “This time, there was a lot of guessing at the beginning, because the science of transmission wasn’t fully developed,” she said. “There shouldn’t be a next time.”

Amyloid plaques are pathological hallmarks of Alzheimer’s disease (AD) — clumps of misfolded proteins that accumulate in the brain, disrupting and killing neurons and resulting in the progressive cognitive impairment that is characteristic of the widespread neurological disorder.
In a new study, published March 2, 2021 in the Journal of Experimental Medicine (JEM), researchers at University of California San Diego School of Medicine, Massachusetts General Hospital and elsewhere have identified a new drug that could prevent AD by modulating, rather than inhibiting, a key enzyme involved in forming amyloid plaques.
In studies using rodents and monkeys, the researchers report the drug was found to be safe and effective, paving the way for possible clinical trials in humans.
“Alzheimer’s disease is an extraordinarily complex and multi-faceted condition that has, so far, defied effective treatment, let alone prevention,” said senior author Steven L. Wagner, PhD, professor in the Department of Neurosciences at UC San Diego School of Medicine. “Our findings suggest a potential therapy that might prevent one of the key elements of AD.”
Amyloid plaques are composed of small protein fragments called amyloid beta (Aβ) peptides. These peptides are generated by enzymes called β-secretase and γ-secretase, which sequentially cleave a protein called amyloid precursor protein on the surfaces of neurons to release Aβ fragments of varying lengths. Some of these fragments, such as Aβ42, are particularly prone to forming plaques, and their production is elevated in patients with mutations predisposing them to early-onset AD.
Several attempts have been made to treat or prevent AD using drugs that inhibit either β-secretase or γ-secretase, but many of these drugs have proved to be highly toxic or unsafe in humans, likely because β-secretase and γ-secretase are required to cleave additional proteins in the brain and other organs.

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Instead, Wagner and colleagues investigated the therapeutic potential of drugs known as γ-secretase modulators or GSMs, which instead of inhibiting the γ-secretase enzyme, slightly alter its activity so that it produces fewer Aβ peptides that are prone to form plaques while continuing to duties cleaving other protein targets.
“GSMs offer the ability to mitigate mechanism-based toxicities associated with γ-secretase inhibitors,” said Wagner.
In the new JEM study, researchers created a novel GSM and tested it on mice, rats and macaques. They found that repeated, low doses of the GSM eliminated Aβ42 production in mice and rats, without causing any toxic side effects. The drug was also safe and effective in macaques, reducing Aβ42 levels by up to 70 percent.
The novel GSM was then tested in a mouse model of early-onset AD, treating the animals either before or shortly after they began to form amyloid plaques. In both cases, the novel GSM decreased plaque formation and reduced plaque-associated inflammation, which is thought to contribute to the development of disease.
The findings suggest that the novel GSM could be used prophylactically to prevent AD, write the authors, either in patients with genetic mutations that increase susceptibility to AD or in cases where amyloid plaques have been detected by brain scans.
“In this study, we have pharmacologically characterized a potent GSM that, based on its preclinical attributes, appears to equal or exceed the potency of any previously tested GSMs,” said co-author Rudolph Tanzi, PhD, professor neurology at Harvard Medical School and director of the Genetics and Aging Research Unit at Massachusetts General Hospital.
“Future clinical trials will determine whether this promising GSM is safe in humans and could be used to effectively treat or prevent Alzheimer’s disease.”
An estimated 5 million Americans are living with AD. The number of people with AD doubles every five years beyond age 65, according to the Centers for Disease Control, with the total number of Americans with the disease projected to nearly triple to 14 million by 2060. Currently, there is no known cure, only symptomatic therapies.

The coronavirus pandemic has drawn new attention to the digital divide, as the need for online schooling and working from home has disproportionately hurt those without computer equipment and skills.
Research by Paul A. Pavlou, dean of the C. T. Bauer College of Business at the University of Houston, found that people with basic Information Technology (IT) skills — including the ability to use email, copy and paste files and work with an Excel spreadsheet — are more likely to be employed, even in jobs that aren’t explicitly tied to those skills.
People with more advanced IT skills generally earned higher salaries, the researchers found. The work is described in Information Systems Research.
“Unemployment and low wages remain pressing societal challenges in the wake of increased automation, more so for traditionally-disadvantaged groups in the labor market, such as women, minorities, and the elderly,” the researchers wrote. “However, workers who possess relevant IT skills might have an edge in an increasingly digital economy.”
The findings, Pavlou said, reinforce the need for robust public policy to ensure people, especially women, older workers and others who are more likely to face employment discrimination, have the basic IT skills needed for the modern working world, since few companies provide on-the-job training in those skills.
“Very few people can get these skills from their employer. Workers are expected to obtain these IT skills themselves, in order to get a job in the first place” he said. “And the less-privileged population they are, the harder time they have obtaining these skills that require computer equipment and internet access.”
That leaves many workers, especially from under-represented populations in the labor market, unable to even apply for work, as more job applications — and now, interviews — are handled online.
In addition to Pavlou, co-authors on the paper include Hilal Atasoy of Rutgers University and Rajiv Banker from Temple University.
The analysis was conducted using two datasets from the Turkish Statistical Institute, and Pavlou said the findings are especially relevant for the developing world, where people are less likely to have IT skills and access to computer equipment than they are in the United States.
But the pandemic has laid bare unequal access to technology in the United States, too, as schools and universities struggle to provide students with computers, internet hotspots and other equipment to continue their educations online.
The work thus has implications for marginalized workers in the United States and other developed countries, Pavlou said. That includes women and older workers, who are more likely to opt out of the labor force if they cannot work from home — jobs that are more likely to require at least basic tech savvy.
“The digital divide is a major societal problem,” Pavlou said. “I think the pandemic will make it even more pronounced. People with basic IT skills will have access to more opportunities, and it is imperative for educational institutions to provide these IT skills, especially in traditionally-disadvantaged populations.”

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A new study has shown that gentle streams of water carrying sound and microscopic air bubbles can clean bacteria from salad leaves more effectively than current washing methods used by suppliers and consumers. As well as reducing food poisoning, the findings could reduce food waste and have implications for the growing threat of anti-microbial resistance.
Salad and leafy green vegetables may be contaminated with harmful bacteria during growing, harvesting, preparation and retail leading to outbreaks of food poisoning which may be fatal in vulnerable groups.
Because there is no cooking process to reduce the microbial load in fresh salads, washing is vital by the supplier and the consumer.
Washing with soap, detergent bleach or other disinfectants is not recommended and the crevices in the leaf surface means washing with plain water may leave an infectious dose on the leaf. Even if chemicals are used, they may not penetrate the crevices.
In this new study, published in the journal Ultrasound in Medicine and Biology, scientists used acoustic water streams to clean spinach leaves directly sourced from the field crop, then compared the results with leaves rinsed in plain water at the same velocity.
Professor Timothy Leighton of the University of Southampton, who invented the technology and led this research, explains: “Our streams of water carry microscopic bubbles and acoustic waves down to the leaf. There the sound field sets up echoes at the surface of the leaves, and within the leaf crevices, that attract the bubbles towards the leaf and into the crevices. The sound field also causes the walls of the bubbles to ripple very quickly, turning each bubble into a microscopic ‘scrubbing’ machine. The rippling bubble wall causes strong currents to move in the water around the bubble, and sweep the microbes off the leaf. The bacteria, biofilms, and the bubbles themselves, are then rinsed off the leaf, leaving it clean and free of residues.”
The results showed that the microbial load on samples cleaned with the acoustic streams for two minutes was significantly lower six days after cleaning than on those treated without the added sound and bubbles. The acoustic cleaning also caused no further damage to the leaves and demonstrated the potential to extend food shelf life, which has important economic and sustainability implications.
Improving how food providers clean fresh produce could have a major role to play in combating the threat of anti-microbial resistance. In 2018 and 2019, there were fatal outbreaks of different strains of E. coli on romaine lettuce in the USA and Canada and samples from humans infected showed strains that are resistant to antibiotics.
University of Southampton PhD student Weng Yee (Beverly) Chong, who was part of the research team added: “I am very grateful to Vitacress and EPSRC for funding my PhD. I came from an engineering background, and took Professor Leighton’s classes, but he told me that I could be a trans-disciplinary PhD student, and become a microbiologist whilst increasingmy engineering skills. I am also very grateful to Sloan Water Technology Ltd.: They opened up their laboratories for use by students like me, so that I can keep working on my experiments. It is an exciting environment to work in because they are doing so much inventive work to combat the pandemic and infections as a whole.”
Previously as part of her PhD Beverly has studied how the technology could reduce the infection risk to horses and other livestock through hay cleaning.
The work was sponsored by Vitacress, whose Group Technical Director Helen Brierley said: “Ensuring food safety for our products is an essential requirement. At Vitacress, we wash our produce in natural spring water, and this type of ground-breaking new technology helps to enhance our process whilst ensuring our commitment to protect the environment is maintained. We are always interested in new developments and are excited to see the results of this research.”

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Positive psychological effects associated with taking small doses of psychedelic drugs are likely the result of users’ expectations, suggests a study published today in eLife.
The study — the largest placebo-controlled trial on psychedelics to date — used an innovative ‘self-blinding citizen science’ approach, where members of the public who were already microdosing implemented their own placebo control following online instructions. The results from the trial may influence future studies in real-world settings.
There has been renewed interest in studying whether psychedelic drugs may be a useful treatment for depression, addiction, obsessive-compulsive disorders and other conditions. Few small studies have previously suggested that microdoses — small doses of psychedelic drugs taken one to three times a week — may improve people’s wellbeing, creativity and overall cognitive performance. But many of the studies lack a control group of participants taking a dummy pill to determine if these positive outcomes are the result of the drug’s action, or the result of the participants’ expectations of a benefit — the so-called placebo effect. “Anecdotal reports about the benefits of microdosing are almost certainly biased by the placebo effect,” says lead author Balázs Szigeti, a research associate at Imperial College London, UK.
Szigeti and his colleagues designed a citizen science study where individuals who were already microdosing could participate online. First, the 191 participants followed a setup procedure that mixed placebo pills with microdose ones. After the setup, the participants had a set of capsules without knowing which were placebo and which were microdose. The authors call this process ‘self-blinding’, as participants lost knowledge of which drug they were taking. The setup included barcodes which, when scanned, linked to the study’s IT infrastructure and allowed the researchers to track who had taken microdoses or placebos. The participants then filled out surveys about their experiences and completed online cognitive tests, while they took the pills over a four-week period.
Participants who were taking the real psychoactive drugs and those unknowingly taking the placebos reported similar psychological benefits. “Our results are mixed: on the one hand, we observed microdosing’s benefits in a wide range of psychological measures; on the other hand, equal benefits were seen among participants taking placebos,” Szigeti explains. “These findings suggest that the benefits are not due to the drug, but rather due to the placebo-like expectation effects. Many participants who reported that they experienced positive effects while taking the placebo were shocked to learn after the study that they hadn’t been taking the real drug.”
The authors caution that the results are not as reliable as the results from a traditional placebo-controlled study, due to participants sourcing their drug from the black market. However, the team’s citizen science approach accurately reflects ‘real-life microdosing’ — that is, how microdosing is done in practice. Additionally, the study cost a fraction of what a traditional clinical study would cost, which may make it a useful first step in assessing whether other popular phenomena can be explained by the placebo effect.
“The successful execution of this study could inspire similar studies in a broad range of scientific or medical contexts,” says senior author David Erritzoe, Clinical Senior Lecturer in Psychiatry at Imperial College London. “Accounting for the placebo effect is important when assessing trends such as the use of cannabidiol oils, fad diets or supplements where social pressure or users’ expectations can lead to a strong placebo response. Self-blinding citizen science initiatives could be used as an inexpensive, initial screening tool before launching expensive clinical studies.”

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In a new study from Shiley Eye Institute at UC San Diego Health, researchers have identified a potential new marker that shows cardiovascular disease may be present in a patient using an optical coherence tomography (OCT) scan — a non-invasive diagnostic tool commonly used in ophthalmology and optometry clinics to create images of the retina. The finding suggests it may be possible to detect heart disease during an eye examination.
In the paper published March 2, 2021 in EClinical Medicine by The Lancet, the research team examined lesions of the retina, the inner-most, light-sensitive layer of the eye, to determine if a cardiovascular disorder may be present.
“The eyes are a window into our health, and many diseases can manifest in the eye; cardiovascular disease is no exception,” said lead author Mathieu Bakhoum, MD, PhD, a physician-scientist and retina surgeon at UC San Diego Health. “Ischemia, which is decreased blood flow caused by heart disease, can lead to inadequate blood flow to the eye and may cause cells in the retina to die, leaving behind a permanent mark. We termed this mark ‘retinal ischemic perivascular lesions,’ or RIPLs, and sought to determine if this finding could serve as a biomarker for cardiovascular disease.”
As part of the study, the team reviewed the records of individuals who received a retinal OCT scan at UC San Diego Health from July 2014 to July 2019. From that cohort, two groups were identified after medical chart review: one consisted of 84 individuals with heart disease and the other included 76 healthy individuals as the study’s control group. An increased number of RIPLs was observed in the eyes of individuals with heart disease.
According to the researchers, the higher number of RIPLs in the eye, the higher the risk for cardiovascular disease.
“The only way we can visualize the smallest blood vessels in the body is in the eye. The retina in particular provides important evidence of the adverse effects of cardiovascular issues, such as high blood pressure,” said Anthony DeMaria, MD, Judith and Jack White Chair in Cardiology and cardiologist at UC San Diego Health. “It’s my hope that the presence of RIPLs in the eye will serve as a marker for cardiovascular disease when patients are undergoing assessment of risk factors for heart disease, or when patients are undergoing evaluation for the suspected presence of heart disease.”
DeMaria said detection of RIPLs could result in identification of cardiovascular disease that would enable early therapy and preventative measures, and potentially reduce numbers of heart attacks or strokes.
A person’s risk for cardiovascular disease is determined by the atherosclerotic cardiovascular disease (ASCVD) risk score calculator, the national guideline developed by the American College of Cardiology. The guideline is considered the gold standard for assessing a patient’s 10-year risk of experiencing a cardiovascular event, such as heart attack or stroke. In the study, researchers found a correlation between the number of RIPLs in a patient’s eye and their ASCVD risk score.
“Individuals with low and borderline ASCVD scores had a low number of RIPLs in their eyes, but as the ASCVD risk increased, so did the number of RIPLs,” said Bakhoum.
Ophthalmologists at UC San Diego Health now consider referring patients to a cardiologist if RIPLs are identified during an OCT scan. The research teams hopes this paper and future studies will result in RIPLs becoming a common ophthalmological marker for identifying potential cardiovascular disease, and incorporated into the overall ASCVD risk score.
“Globally, cardiovascular disease is the number one cause of death and unfortunately many people are unaware they may have heart issues,” said Bakhoum. “The key in preventing this is early detection and treatment. It’s our hope that by identifying RIPLs as a marker for cardiovascular disease providers will be able to identify heart issues before a catastrophic event, such as a heart attack or a stroke, occurs.”

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Materials provided by University of California – San Diego. Original written by Jeanna Vazquez. Note: Content may be edited for style and length.

Disruptions in the circadian rhythms in lung cells may explain why adults who survived premature birth are often more at risk of severe influenza infections, suggests a study in mice published today in eLife.
Dramatic improvements in the care of infants born prematurely have allowed many more to survive into adulthood. Yet ex-preemies can face several long-term side effects of the life-saving care they received. The study suggests potential new approaches to treating lasting lung problems in those born prematurely.
Many premature infants are not able to breathe on their own and require oxygen to survive. But receiving too much oxygen may cause lasting damage to the lung that makes them more prone to severe flu infection later in life. In a previous study*, senior author and neonatologist Shaon Sengupta, and her colleagues at the Children’s Hospital of Philadelphia Research Institute, Pennsylvania, US, found that susceptibility to flu in mice depended on the time of day when they caught the infection. Mice that caught the infection when they became active at dusk were more likely to die, while those infected as they went to sleep at dawn were more likely to survive. This suggests that the circadian clock, which controls the daytime and nighttime activities of the body, may offer some protection against flu.
“Given these previous findings, we wanted to see if the severity of flu infection in former premature infants may be caused by disruptions to their circadian clock,” says Yasmine Issah, a former Research Technician at the Children’s Hospital of Philadelphia Research Institute, and co-first author of the current study alongside Postdoctoral Research Fellow Amruta Naik.
The team began by showing that the time of day when exposure to flu occurred did not affect susceptibility to infection in adult mice that were exposed to high levels of oxygen as newborns. This suggests that these mice had lost their circadian clock-based flu protection.
But when the team tested the ability of the animals to readjust to a normal day-night schedule after living in dim light for several weeks, they found the animals had no problems — suggesting that their central circadian clock in the brain, which is regulated by exposure to daylight, was working normally.
To find out if the circadian problems were restricted to lung cells, which have their own circadian clocks separate from the brain clock, the team removed a key circadian clock gene called Bmal1 in the lung cells of normal adult mice. They eliminated the gene in the same lung cells that are damaged in newborn mice given high levels of oxygen. As with the mice that had been exposed to high oxygen as newborns, the adult animals with the deleted gene were equally susceptible to flu at dawn or dusk.
“Our findings suggest that adverse early-life exposures can disrupt the lung circadian clock,” concludes Sengupta, an attending neonatologist at the Children’s Hospital of Philadelphia Research Institute. “Those born prematurely are uniquely vulnerable to this faulty development of their circadian network, and this is a new paradigm for understanding the lung problems that persist into adulthood in ex-preemies. These findings could pave the way for potential new treatments that work by improving the circadian health in adults born prematurely.”

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Materials provided by eLife. Note: Content may be edited for style and length.