Day: November 12, 2024

Categories : Cancer NeurologyTags : Leave a comment

A Way to Make Glioblastoma Cells Visible to Immune Cells

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MRI scan showing brain cancer. Credit: Michelle Monje, MD, PhD, Stanford University

Patients with glioblastoma typically survive less than two years after diagnosis, even with cutting-edge therapies. The latest immunotherapies have been unsuccessful, likely because glioblastoma cells have few, if any, natural targets for the immune system to attack.

In a cell-based study, scientists at Washington University School of Medicine have forced glioblastoma cells to display immune system targets, potentially making them visible to immune cells and newly vulnerable to immunotherapies. The strategy involves a combination of two drugs, each already FDA-approved to treat different cancers.

The study is online in the journal Nature Genetics.

“For patients whose tumours do not naturally produce targets for immunotherapy, we showed there is a way to induce their generation,” said co-senior author Ting Wang, PhD, professor of medicine and Department of Genetics head at WashU Medicine. “In other words, when there is no target, we can create one. This is a very new way of designing targeted and precision therapies for cancer. We are hopeful that in the near future we will be able to move into clinical trials, where immunotherapy can be combined with this strategy to provide new therapeutic approaches for patients with very hard-to-treat cancers.”

To create immune targets on cancer cells, Wang has focused on stretches of DNA in the genome known as transposable elements. In recent years, transposable elements have emerged as a double-edged sword in cancer, according to Wang. His work has shown that transposable elements play a role in causing tumours to develop even as they present vulnerabilities that could be exploited to create new cancer treatment strategies.

For this study, Wang’s team took advantage of the fact that transposable elements naturally can cause a tumour to churn out random proteins that are unique to the tumour and not present in normal cells. Called tumour antigens or neoantigens, these unusual proteins could be the targets for immunotherapies, such as checkpoint inhibitors, antibodies, vaccines and genetically engineered T cell therapies.

Even so, some tumours, including glioblastoma, have few immune targets produced naturally by transposable elements. To address this, Wang and his colleagues, including co-senior author Albert H. Kim, MD, PhD, neurosurgery professor, have demonstrated how to purposely force transposable elements to produce immune system targets on glioblastoma cells that normally lack them.

The researchers used a combination of two drugs that influence the epigenome, which controls gene activation. When treated with the two epigenetic therapy drugs, the tightly packed DNA molecules of the glioblastoma cells unfurled, triggering transposable elements to begin making the unusual proteins that could be used to target the cancer cells. The two drugs were decitabine, which is approved to treat myelodysplastic syndromes, a group of blood cancers; and panobinostat, which is approved for multiple myeloma, a cancer of white blood cells.

Before investigating this strategy in people, the researchers are seeking ways to target the epigenetic therapy so that only the tumour cells are induced to make neoantigens. In the new study, the researchers cautioned that normal cells also produced targets when exposed to the two drugs. Even though normal cells didn’t produce as many neoantigens as the glioblastoma cells did, Wang and Kim said there is a risk of unwanted side effects if normal cells create these targets as well.

In ongoing work, Wang and Kim are investigating how to use CRISPR molecular editing technology to induce specific parts of the genome in cancer cells to produce the same neoantigens from transposable elements that are common across the human population. Such a strategy could give many patients’ tumours – even different cancer types – the same targets that could respond to the same immunotherapy, while sparing healthy cells. There are then multiple possible ways to go after such a shared target, including checkpoint inhibitors, vaccines, engineered antibodies and engineered T cells.

Source: Washington University School of Medicine

Categories : Metabolic DisordersTags : Leave a comment

How Organisations Can Support Mobile Workforces with Diabetes – From Prevention to Management

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Photo by Nataliya Vaitkevich on Pexels

As global mobility surges, managing chronic conditions like diabetes during travel has become a significant concern. Diabetes remains one of the fastest-growing global public health issues1,affecting approximately 422 million people worldwide and causing 1.5 million deaths annually.2 International SOS, the world’s leading health and security services company, has reported a significant year-on-year increase in diabetes-related assistance cases over the past three years, with a 28% increase in 2022 and a 32% increase in 2023.

Meanwhile, year-to-date 2024 data indicates a further uptick.3 With World Diabetes Day approaching on 14 November, organisations are urged to support diabetes prevention and management strategies. This year’s theme, ‘Breaking Barriers, Bridging Gaps’4 highlights the need for equitable, comprehensive and affordable diabetes care.

Dr Katherine O’Reilly, Regional Medical Director at International SOS, emphasises the importance of comprehensive health strategies: “It is important for organisations to understand the unique challenges that employees with diabetes face, particularly when travelling. By recognising these specific needs, companies can provide the necessary support and resources to help their employees manage their condition effectively. This ensures that employees can maintain their health and productivity, even when they are on the go. With thoughtful planning and the right resources, organisations can help their employees navigate the complexities of diabetes, fostering a supportive and inclusive work environment.”

People with diabetes face a double burden: a higher risk of life-threatening conditions like heart attack, stroke, and kidney failure, compounded by the psychological toll of diabetes distress. Individuals with diabetes are two to three times more likely to experience depression compared to those without the condition.5 These challenges can significantly impact employee wellbeing, leading to increased absenteeism, reduced productivity, and higher healthcare costs for employers.

According to The International Diabetes Federation (IDF), the global healthcare costs for individuals living with diabetes are expected to exceed $1054 billion by 2045.6 Furthermore, the prevalence of diabetes is projected to rise, with 643 million people affected by 2030, and 783 million by 2045.7 With this rising prevalence, it is crucial for organisations to implement strategies that help their workforce manage and prevent this chronic condition. Minor adjustments can reduce absenteeism, increase productivity, concentration and energy levels, and reduce the chance of on-the-job injury.

Dr Katherine O’Reilly continues, “Early diagnosis is crucial. Raising awareness about diabetes symptoms can prompt people to get screened, enabling early detection and intervention to prevent or delay its onset.  This proactive approach can prevent undiagnosed diabetes from causing severe health complications, affecting various organ systems, including eye damage, heart and kidney disease, nerve damage and poor wound healing. By prioritising employee health, organisations can enhance productivity and foster a more engaged and resilient workforce. This approach also promotes a positive work environment and supports overall employee wellbeing.”


International SOS offers five tips for organisations to support employees in managing and preventing diabetes:

  1. Education and awareness: Increase awareness about diabetes symptoms to encourage early diagnosis and effective management, thereby preventing severe health complications.
  2. Provide comprehensive health solutions: Offer resources such as dietary guidelines, exercise programmes and regular health screenings to help employees manage their diabetes.
  3. Supportive culture and policies: Develop and implement policies allowing for flexible work schedules and access to medical care while travelling. Foster a culture that prioritises health and wellbeing by accommodating regular meals and exercise, and ensuring employees have time to rest and recover from travel.
  4. Promote a healthy lifestyle: Offer guidance on maintaining a healthy diet and regular exercise. Provide resources such as a list of healthy meal options and tips for finding nutritious food in different locations.
  5. Facilitate health monitoring and provide adjustments: Ensure employees have scheduled breaks to take medication, check blood sugar levels and eat regular meals. Provide a private space for insulin administration and other medical needs.

  1. Hossain, J., Al-Mamun, Islam, R. Health Science Reports | Diabetes mellitus, the fastest growing global public health concern: Early detection should be focused (2024)
  2. World Health Organization | Diabetes
  3. International SOS Assistance Tracker Data (2021 – 2024)
  4. World Health Organization | World Diabetes Day 2024
  5. CDC | Diabetes and Mental Health (2024)
  6. International Diabetes Federation | Diabetes Atlas Report 2021
  7. Parker ED, Lin J, Mahoney T, Ume N, Yang G, Gabbay RA, ElSayed NA, Bannuru RR. | Economic Costs of Diabetes in the U.S. in 2022. Diabetes Care (2024)
Categories : Cardiovascular Disease Emergency MedicineTags : Leave a comment

Bystander CPR up to 10 Minutes after Cardiac Arrest may Protect Brain Function

On By ModernMedia
Photo by www.testen.no on Unsplash

The sooner a lay rescuer (bystander) starts cardiopulmonary resuscitation (CPR) on a person having a cardiac arrest at home or in public, up to 10 minutes after the arrest, the better the chances of saving the person’s life and protecting their brain function, according to preliminary research to be presented at the American Heart Association’s Resuscitation Science Symposium 2024.

Cardiac arrest, which occurs when the heart malfunctions and abruptly stops beating, is often fatal without quick medical attention such as CPR to increase blood flow to the heart and brain. More than 357 000 out-of-hospital cardiac arrests happen each year in the US, with a 9.3% survival rate. “Our findings reinforce that every second counts when starting bystander CPR and even a few minutes delay can make a big difference,” said first author Evan O’Keefe, MD, a cardiovascular fellow at Saint Luke’s Mid America Heart Institute and the University of Missouri-Kansas City. “If you see someone in need of CPR, don’t dwell on how long they’ve been down, your quick actions could save their life.”

The study analysed nearly 200 000 cases of witnessed out-of-hospital cardiac arrest to determine whether initiating CPR within different time windows, compared to outcomes with no bystander CPR administered, made a difference in survival and brain function after hospital discharge.

“We found that people who received bystander CPR within the first few minutes of their cardiac arrest were much more likely to survive and have better brain function than those who didn’t,” O’Keefe said. “The longer it took for CPR to start, the less survival benefit one received. However, even when CPR was started up to 10 minutes after cardiac arrest, there was still a significant survival benefit compared to individuals who did not receive CPR from a bystander.”

Results also found: 

  • People who received CPR within two minutes of out-of-hospital cardiac arrest had an 81% higher rate of survival to release from the hospital and 95% higher rate of surviving without significant brain damage compared to people who did not receive bystander CPR.
  • Even people who received bystander CPR up to 10 minutes after cardiac arrest were 19% more likely to survive to hospital discharge and 22% more likely to have a favorable neurological outcome than those who did not receive bystander CPR at all.
  • For those who did not receive bystander CPR, about 12% survived to be released from the hospital, and more than 9% survived without significant brain damage or major disabilities. When bystander CPR was initiated more than 10 minutes after cardiac arrest, bystander CPR, compared to not receiving the lifesaving assistance, was no longer associated with improved survival.

“These results highlight the critical importance of quick action in emergencies. It suggests that we need to focus on teaching more people how to perform CPR, and we also need to emphasise ways to get help to those suffering cardiac arrest faster,” O’Keefe said. “This might include more widespread CPR training programs, as well as better public access to automated external defibrillators (AEDs) and improved dispatch systems.”

O’Keefe noted that future research could explore how technology (like apps that alert nearby trained bystanders or alert dispatchers to likely cardiac arrest) may help to reduce the time to first intervention, information that could be important for emergency dispatchers and policymakers in the development of public interventions for cardiac arrest.

“This study highlights the need for prompt recognition and treatment of cardiac arrest by bystanders. Time is of the essence when a cardiac arrest occurs, and late interventions can be as ineffective as no intervention. Community education and empowerment are critical for us to save lives,” said American Heart Association volunteer expert Anezi Uzendu, MD, an interventional cardiologist at the University of Texas Southwestern Medical Center in Dallas and a cardiac arrest survivor.

A limitation of the study includes that the average time of arrival for emergency medical technicians (EMTs) to the person having cardiac arrest was roughly 10 minutes. This means that in this study, the people who received bystander CPR 10 minutes after their cardiac arrest were likely being compared to a group receiving professional medical attention.

Study details and background:

  • The study identified 160 822 witnessed out-of-hospital cardiac arrests that occurred from 2013-2022.  Among the people whose data was analysed, the average age was 64 years old and about 34% were women.
  • Researchers used data from the Cardiac Arrest Registry to Enhance Survival (CARES), a national, web-based health registry focused on helping communities improve care for and survival of out-of-hospital cardiac arrest.
  • The research categorized time to initiation of bystander CPR in two-minute intervals and analysed the link between each time interval, compared to the group who did not receive CPR, with survival to hospital discharge and favourable neurological survival, or surviving with minor disabilities.

Source: American Heart Association

Categories : Mental HealthTags : Leave a comment

Dogs and Owners Match Their Heart Rate Variability

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Photo by Pauline Loroy on Unsplash

A study at the University of Jyväskylä showed that the heart rate variability of a dog and its owner adapt to each other during interaction. High heart rate variability is associated with relaxation, while low heart rate variability indicates stimulation. The study, published in Scientific Reports, deepens our understanding of the emotional connection between a dog and its owner, including its underlying physiological mechanisms.

Emotional connection enhances interaction in human relationships. Emotional synchronisation in the interaction between a child and a parent is essential for affective attachment. The relationship between a dog and its owner is also based on attachment, but little is known about its physiological mechanisms.

The heart rate variability of a dog and its owner adapt to each other

In a study conducted at the University of Jyväskylä, at the Department of Psychology and Jyväskylä Centre for Interdisciplinary Brain Research, it was found that the heart rate variability of a dog and its owner are interconnected during interaction. Heart rate variability, in other words, the variation in the heartbeat intervals, indicates the state of the autonomic nervous system. High heart rate variability is associated with a state of relaxation and recovery, while low heart rate variability indicates stimulation or strain, such as stress during an exam or sport performance. In this study, the owner’s high heart rate variability was connected to the dog’s high heart rate variability, and vice versa. In addition, the physical activity levels of a dog and its owner mutually adapted to each other during the study. 

Different connections for activity and heart rate variability

The connections of heart rate variability and activity levels between a dog and its owner were monitored during specific interaction tasks. Both heart rate and activity level were interconnected between dogs and their owners, but at different times. During free-form resting periods, the owner’s high heart rate variability was connected to the dog’s high heart rate variability. In other words, when the owner was relaxed the dog was also relaxed. Moreover, the owner’s and dog’s activity levels were similar during the given tasks, such as playing. Although it is known that physical activity has an impact on heart rate, the strongest connections of these variables between dog and owner were found in different situations and do not fully explain each other. This suggests that the connection in heart rate variability reflects the synchrony of emotional state rather than of activity levels.

“The interconnection in heart rate variability between the dog and its owner during resting periods may be explained by the fact that in those instances there were no external tasks, but the counterparts could react more to each other’s state in a natural way,” says Doctoral Researcher Aija Koskela. 

Owner’s temperament is connected to the dog’s heart rate variability

The study also investigated various background factors for the interconnection of the heart rate variability of the dog and its owner. Bigger dogs had higher heart rate variability. In addition, the dog’s high heart rate variability was also explained by the owner’s negative affectivity, a temperament trait that reflects the person’s tendency to become easily concerned about negative things. This type of owner tends to develop a strong emotional bond with the dog, and therefore the shepherd dogs of this study possibly had a higher sense of safety with these owners. 

The dog also influences the owner

A surprising finding in the study was that the owner’s heart rate variability was best explained by the dog’s heart rate variability, even though also the owner’s activity level and body mass index, which are known to impact heart rate, were taken into account in the analysis.

“We exceptionally investigated both a dog’s and its owner’s heart rate and activity level simultaneously, whereas previous studies have commonly focused either on the human’s or the dog’s perspective,” says the leader of the study, Academy Research Fellow Miiamaaria Kujala. “The challenging research setting gives a better opportunity to investigate interactive aspects.”

This study indicates that the emotional states of dogs and their owners as well as the reactions of their nervous system become partially adapted to each other during interaction. The same mechanisms that strengthen human affective attachment also seem to support the relationship between a dog and its owner. This study deepens our understanding about interaction between species and about the meaning of emotional connection between dogs and humans. 

Interaction research involved dogs bred for cooperation

The study was funded mainly by the Research Council of Finland and the Agria & Svenska Kennelklubben Research Fund. It involved altogether 30 voluntary dog owners with their dogs. The dogs represented breeds refined for cooperating with humans, such as sheep dogs and retrievers. The research findings are in line with previous studies, which have suggested that breeds selected for cooperation are particularly sensitive to react to their owners’ behaviour and personality traits. Next, the project will seek to shed light more specifically on the influential mechanisms involved in this phenomenon.

Source: University of Jyväskylä

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Beta Blockers may Also Cause Depression for Cardiac Patients

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Photo by Towfiqu Barbhuiya on Unsplash

All patients who have had a heart attack are typically treated using beta blockers. According to a Swedish study conducted earlier this year, this drug is unlikely to be needed for those heart patients who have a normal pumping ability. Now a sub-study at Uppsala University shows that there is also a risk that these patients will become depressed by the treatment.

“We found that beta blockers led to slightly higher levels of depression symptoms in patients who had had a heart attack but were not suffering from heart failure. At the same time, beta blockers have no life-sustaining function for this group of patients,” says Philip Leissner, a doctoral student in cardiac psychology and the study’s first author. The study was published in European Heart Journal Acute Cardiovascular Care.

Beta blockers are drugs that block the effects of adrenaline on the heart and have been used for decades as a basic treatment for all heart attack patients. In recent years, their importance has started to be questioned as new, successful treatments have begun to be developed. This is mainly the case for heart attack patients who do not suffer from heart failure.

The researchers wanted to look at the side effects of beta blockers, that is, whether they affect anxiety and depression levels. This is because older research and clinical experience suggests that beta blockers are linked to negative side effects such as depression, difficulty sleeping and nightmares.

Earlier this year, a major national study was conducted in Sweden, which found that those who received beta-blocking drugs were not protected from relapse or death compared to those who did not receive the drug. Leissner and his colleagues based their research on these findings and conducted a sub-study. It ran from 2018 to 2023 and involved 806 patients who had had a heart attack but no problems with heart failure. Half were given beta blockers and the other half were not. About 100 of the patients receiving beta blockers had been taking them since before the study, and the researchers observed more severe symptoms of depression in them.

“Most doctors used to give beta blockers even to patients without heart failure, but as the evidence in favour of doing so is no longer so strong, this should be reconsidered. We could see that some of these patients appear to be more at risk of depression. If the drug doesn’t make a difference to their heart, then they are taking it unnecessarily and at risk of becoming depressed,” adds Leissner.

Source: Uppsala University