Tag: 23/2/22

Researchers Identify a Key Regulatory Mechanism in Inflammation

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A newly published study has identified a key regulatory mechanism in inflammation that may lead to new targets for resolving that inflammation –and the inflammation of patients with sepsis, cancer and COVID.

In the journal PNAS, scientists reported their discovery of a regulatory pathway for immune response after infection or injury, such as burns. Dysregulation of this pathway could differentiate those who are at risk of fatal sepsis or help identify targets to resolve this unregulated inflammation.

“We are very excited about the findings in this paper and the far-reaching impacts it could have on understanding a key regulatory step in the immune response,” said co-lead author Cindy McReynolds, who holds a doctorate in pharmacology and toxicology.

In a rodent model, the research team found that the metabolites of linoleic acid formed by the enzyme, soluble epoxide hydrolase (sEH), drive damaging inflammation after injury. These metabolites, known as lipid mediators, regulate inflammation, blood pressure and pain. Drugs that inhibit the sEH enzyme and reduce inflammation could lead to better outcomes.

“Our previous work identified that these same lipid mediators were up-regulated in severe COVID infections, and we are now finding that these compounds play a role in modulating the immune response so that the body is unable to fight infection or respond properly to trauma without leading to a potentially fatal overreaction,” said Dr McReynolds.

“This dysregulation has fatal consequences in serious diseases such as COVID, cancer, sepsis, burn, where fatality rates can be as high as 40 percent in severe cases,” she said. “An understanding of these pathways can help identify patients at risk of developing serious disease or identify new therapeutic targets for treatment.”

“The immunological disbalance we see in many cases of severe burn injury, trauma and sepsis pose a huge clinical challenge as we lack the understanding of how to diagnose and treat it,” explained co-lead author Dr Christian Bergmann. “With this work, we reveal an important mechanism how immune cells are functionally disabled by sEH-derived metabolites of linoleic acid.”

“The natural compounds we are studying in this paper are metabolites of linoleic acid (LA), an essential fatty acid the body needs in very small amounts to survive and is only available through the diet,” Dr McReynolds elaborated. “At lower concentrations, these metabolites are necessary for regulating thermogenesis and heart health but promote inflammation at higher concentrations. LA is more stable and much cheaper than longer chain polyunsaturated fatty acids, so heavily processed foods have higher LA content to increase shelf-life. Additionally, agricultural practices, such as feeding animals corn-based diets, have increased LA in meats and dairy products.”

“As a result, we are consuming the highest amount of linoleic acid and have the highest recorded concentration of LA in our fatty tissue in human history,” McReynolds said. “As our bodies respond to stress or disease, we metabolise LA into the regulatory metabolites that were monitored in this paper. At higher concentrations, the immune system was unable to properly respond to infection, thereby promoting a sustained immune response. These observations are important in inflammatory-driven diseases, such as sepsis and COVID, but could also be important in understanding many of the increased chronic diseases we are seeing in our population.”

Source: UC Davis

‘Huge Deficit’ in Data for Psilocybin’s Interaction with Existing Medication

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Photo by Timothy Dykes on Unsplash

As the US state of Oregon becomes the first to permit psilocybin in clinical use, a new systematic evidence review reveals a lack of scientific research describing the interactions between widely used psychiatric medications and psychedelics like psilocybin and MDMA. The review was published in the journal Psychopharmacology.

The scarcity of data is problematic for people believed to benefit most from psychedelics: those with mental health conditions such as depression, anxiety and post-traumatic stress disorder.

“There’s a huge deficit in the scientific literature,” said lead author Aryan Sarparast, MD, assistant professor of psychiatry at the Oregon Health and Science University. “There’s a major incongruence between the public enthusiasm and exuberance with psychedelic substances for mental health issues – and what happens when they combine with the existing mental health treatments that we have now.”

The researchers decided to conduct the evidence review because they wanted to learn more about interactions between widely prescribed medications such as antidepressants and psychedelics, including MDMA and psilocybin.

They found a total of 40 studies dating back to 1958, including 26 from randomised controlled studies, 11 case reports and three epidemiologic studies.

Only one study was found that examined how psilocybin interacts with antidepressant medications. A/Prof Sarparast also noted that all of the clinical trials were conducted with healthy volunteers who were administered a psychiatric medication and a psychedelic at the same time – clearly showing a need for further research into combining pharmaceutical medications with psilocybin.

A/Prof Sarparast said he is concerned that the lack of evidence will lead many providers to direct patients to taper off existing medications before being offered clinical psilocybin therapy. In Oregon rules are being drawn up to permit the clinical use of psilocybin products and services from next year.

Patients with mental health conditions might well benefit from psilocybin therapy, but A/Prof Sarparast said he is concerned about the implications of stopping existing psychiatric treatment in order to receive psilocybin services. Vulnerable people may end up being forced into choosing between their existing medical treatment or psilocybin services.

“That’s a very, very tough place to be,” A/Prof Sarparast said.

A considerable amount of important data exists that is not captured in a literature review related to real-world use, noted co-author Christopher Stauffer, MD, assistant professor of psychiatry in the OHSU School of Medicine and a physician-scientist at the VA Portland Health Care System.

“Psilocybin has been around in Western society since the late 1950s, before many of our psychiatric medications have existed,” A/Prof Stauffer said. “Nonetheless, people attempting to navigate Oregon’s psilocybin services in the context of ongoing psychiatric treatment should work closely with knowledgeable professionals.”

Source: Oregon Health & Science University

Sound Waves Used to Regrow Bone

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In a significant advance for the field of tissue engineering, researchers have used sound waves to turn stem cells into bone cells, a technology which may help regrow bone lost by cancer or disease.

Described in the journal Small, the innovative stem cell treatment from researchers at RMIT University offers a smart way forward for overcoming some of the field’s biggest challenges, through the precision power of high-frequency sound waves.

Tissue engineering is an emerging field that aims to rebuild bone and muscle by harnessing the human body’s natural ability to heal itself. A key challenge in regrowing bone is having sufficient amounts of bone cells that can thrive once implanted in the target area.

So far, turning stem cells into bone cells has needed complicated and expensive equipment, making widespread clinical use unrealistic.

The few clinical trials trying to regrow bone mostly used stem cells painfully extracted from a patient’s bone marrow.

In a new study published in the journal Small, the RMIT research team showed stem cells treated with high-frequency sound waves turned into bone cells quickly and efficiently.

Importantly, the treatment was effective on multiple types of cells including fat-derived stem cells, which are far less painful to extract from a patient.

Co-lead researcher Dr Amy Gelmi said the new approach was faster and simpler than other methods.

“The sound waves cut the treatment time usually required to get stem cells to begin to turn into bone cells by several days,” said Dr Gelmi. “This method also doesn’t require any special ‘bone-inducing’ drugs and it’s very easy to apply to the stem cells.

“Our study found this new approach has strong potential to be used for treating the stem cells, before we either coat them onto an implant or inject them directly into the body for tissue engineering.”

The high-frequency sound waves used in the stem cell treatment were generated on a low-cost microchip device developed by RMIT.

Co-lead researcher Distinguished Professor Leslie Yeo and his team have spent over a decade researching the interaction of sound waves at frequencies above 10MHz with different materials.

The sound wave-generating device they developed can be used to precisely manipulate cells, fluids or materials.

“We can use the sound waves to apply just the right amount of pressure in the right places to the stem cells, to trigger the change process,” Prof Yeo said.

“Our device is cheap and simple to use, so could easily be upscaled for treating large numbers of cells simultaneously – vital for effective tissue engineering.”

The next stage in the research is investigating methods to upscale the platform, working towards the development of practical bioreactors to drive efficient stem cell differentiation.

Source: RMIT

Hypertension Risk for Women After Sexual Assault or Harassment

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A new study has found that women who have experienced sexual assault or harassment are at higher long-term risk of developing hypertension than women who have not.

The study appears in the Journal of the American Heart Association.

In the US, nearly 43% of women aged 20 and older have hypertension. Defined as a blood pressure of 130/80mmHg or higher, hypertension is a major risk factor for cardiovascular disease – the number one killer of women, causing one in three deaths each year.

“We know that experiences of sexual violence in the form of sexual assault and workplace sexual harassment are common, and that women are disproportionately victims of such violence, with 13–44% of women reporting sexual assault and up to 80% of women reporting workplace sexual harassment,” said study author Rebecca B. Lawn, PhD. “However, exposure to sexual violence is not widely recognized as a contributor to women’s cardiovascular health. We felt it was important to investigate the relationship among common forms of sexual violence with the risk of developing hypertension. These links could help in the early identification of factors that influence women’s long-term cardiovascular health.”

In this study, researchers analysed data over the course of seven years beginning with a 2008 follow-up of the Nurses’ Health Study II, an ongoing cohort study of US women. The 2008 follow-up measured the incidence of sexual violence and other trauma exposure, as well as post-traumatic stress disorder (PTSD) and symptoms of depression, among a subset of 54 703 of the study’s original participants.

From that subset, Lawn and colleagues analysed data for 33 127 women (95% non-Hispanic white women; average age of 53 years at the beginning of the 2008 follow-up) who had no history of hypertension or had not taken medication for high blood pressure as of the start of the 2008 follow-up.

The analyses found:

  • At the seven-year follow-up in 2015, about 1 in 5 (nearly 7100) of the women self-reported they had developed hypertension, validated with medical records.
  • Sexual assault and workplace sexual harassment were common, with lifetime prevalence of 23% for sexual assault and 12% for workplace sexual harassment; 6% of women reported experiencing both.

Compared to women with no history of sexual assault or harassment, women who reported having experienced both had the greatest increased hypertension risk (21%), followed women who reported experiencing workplace sexual harassment (15%) and an women who reported experiencing sexual assault (11%).

“We did not find any association of increased risk for hypertension among women who had a history of other types of trauma and who did not experience sexual violence, suggesting that increased hypertension risk does not appear to be associated with all trauma exposure,” Dr Lawn said. “Our finding that experiencing both sexual assault and workplace sexual harassment had the highest risk of hypertension underscores the potential compounding effects of multiple sexual violence exposures on women’s long-term cardiovascular health.”

Dr Lawn observed screening for partner violence by primary care clinicians is becoming more common, sexual violence overall is not recognised as a risk factor among women for developing cardiovascular disease.

“These results suggest that screening for a broader range of experiences of sexual violence in routine health care, including sexual harassment in the workplace, as well as verbal harassment or assault, and being aware of and treating potential cardiovascular health consequences may be beneficial for women’s long-term health,” she said. “Reducing sexual violence against women, which is important in its own right, may also provide a strategy for improving women’s lifetime cardiovascular health.”

There are several limitations to the study, including memory biases in recall of sexual violence. The sexual assault and harassment had no measures of severity or timing. Most of the women in the study were white women in the nursing field, limiting generalisability.

“We hope future studies will examine these questions with more detailed information on sexual and other forms of violence. These questions need to be investigated in more diverse groups of people of various ages, races and ethnic backgrounds and gender,” Dr Lawn said. “Although women are disproportionately victims of sexual violence, men are also victims and the physical health implications of experiences of sexual violence against men warrants further investigation.”

Source: American Heart Association

Greenspaces in Hospitals Calm Patients and Visitors

It can be stressful and time-consuming for patients and visitors to become accustomed to navigating large, unfamiliar hospitals, and so an architecture researcher tested a simple remedy: to let nature in with the use of indoor greenspaces and large windows.

Research conducted by West Virginia University’s associate professor Shan Jiang showed that introducing nature into large hospitals can humanise the institutional environment and reduce the stress of patients, visitors and healthcare providers.

Prof Jiang made use of immersive virtual environments for a controlled experiment that asked participants to complete various wayfinding tasks in a simulated hospital.

Though participants saw the same layout, one group encountered large windows and nature views among the corridor walls. The control group meanwhile saw solid walls without any daylight or views of nature, more like a typical modern hospital. Participants in the greenspace group used shorter time and walked less distance to complete wayfinding tasks.

“In terms of spatial orientation and wayfinding, window views of nature and small gardens can effectively break down the tedious interiors of large hospital blocks,” Prof Jiang said, “and serve as landmarks to aid people’s wayfinding and improve their spatial experience.”

In the greenspace group, participants’ mood states, particularly anger and confusion, were also found to be “significantly relieved”.

Prof Jiang’s findings are published in the Health Environments Research and Design Journal.

Based on prior research, it’s estimated that a patient or hospital visitor must go through at least seven steps in the wayfinding process to arrive at the final destination. WVU’s Center for Health Design cites wayfinding issues as an environmental stressor and a concerning topic in healthcare design.

Prof Jiang said that she was prompted to do the study by those factors, coupled with her own personal experiences (her family members have worked in healthcare) and others’ accounts of feeling lost in hospitals.

“Large hospitals can be visually welcoming but the functionality and internal circulation are indeed complex and confusing,” she said.

Greenspaces positioned at key decision points, such as main corridors or junctions, can help improve navigation.

With a background in landscape architecture, Jiang has been interested in the immediate surroundings of people in a smaller scope, particularly the indoor-outdoor relationship and the boundaries between architecture and landscapes.

Gardens and plants also tend to have strong therapeutic effects on people, she found.

“You may explain such therapeutic effects from multiple perspectives: people’s colour/hue preferences tend to range from blue to green, nature and plants are positive distractions that could restore people’s attentional fatigue, and human beings could have developed genetic preference of greenery from evolutionary perspectives,” Prof Jiang said. “All mechanisms together contribute to the positive experience when looking at gardens and nature views.”

Prof Jiang noted that many European hospitals have successfully integrated “hospital in a park” concepts. In the United States, the Lucile Packard Children’s Hospital Stanford in California has patios and window nooks in every patient room, and most rooms have direct views of a large healing garden, she said. The Alder Hey Children’s Hospital in the UK was literally built in a park.

Source: West Virginia University

Do People’s Lives ‘Flash Before Their Eyes’ When They Die?

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By chance, neuroscientists were able to record the activity of a dying human brain and discovered brain wave patterns similar to dreaming, memory recall, and meditation. An analysis of this case, reported in Frontiers in Aging Neuroscience suggests a possible explanation for near-death experiences.

Imagine reliving your entire life in the space of seconds. Like a flash of lightning, you are outside of your body, watching memorable moments you lived through. This process, known as ‘life recall’, can be similar to what it’s like to have a near-death experience. What happens inside your brain during these experiences and after death are questions that have puzzled neuroscientists for centuries. However, the present study suggests that your brain may remain active and coordinated during and even after the transition to death, and may in fact be programmed to orchestrate the whole ordeal.

When an 87-year-old patient developed epilepsy, Dr Raul Vicente of the University of Tartu, Estonia and colleagues used continuous electroencephalography (EEG) to detect the seizures and treat the patient. During these recordings, the patient had a heart attack and passed away. This unexpected event allowed the scientists to record the activity of a dying human brain for the first time ever.

“We measured 900 seconds of brain activity around the time of death and set a specific focus to investigate what happened in the 30 seconds before and after the heart stopped beating,” said Dr Ajmal Zemmar, a neurosurgeon at the University of Louisville, US, who organised the study.

“Just before and after the heart stopped working, we saw changes in a specific band of neural oscillations, so-called gamma oscillations, but also in others such as delta, theta, alpha, and beta oscillations.”

Brain oscillations (aka ‘brain waves’) are patterns of rhythmic brain activity normally present in living human brains. These different types of oscillations, including gamma, are involved in high-cognitive functions, such as concentrating, dreaming, meditation, memory retrieval, information processing, and conscious perception, just like those associated with memory flashbacks.

“Through generating oscillations involved in memory retrieval, the brain may be playing a last recall of important life events just before we die, similar to the ones reported in near-death experiences,” Dr Zemmar speculated. “These findings challenge our understanding of when exactly life ends and generate important subsequent questions, such as those related to the timing of organ donation.”

Though this is the first study to ever measure live brain activity during the process of dying in humans, similar changes in gamma oscillations have been previously recorded in rats kept in controlled environments. This raises the possibility that, during death, the brain organises and executes a biological response that could be conserved across species.

The interepretation of this however is complicated by the fact that these measurements are based on a single case and stem from the brain of a patient who had suffered injury, seizures and swelling. Nonetheless, Dr Zemmar plans to investigate more cases and sees these results as a source of hope.

“As a neurosurgeon, I deal with loss at times. It is indescribably difficult to deliver the news of death to distraught family members,” he said.

“Something we may learn from this research is: although our loved ones have their eyes closed and are ready to leave us to rest, their brains may be replaying some of the nicest moments they experienced in their lives.”

Source: Frontiers

Heart Attack Survivors at Lower Risk of Parkinson’s

Credit: American Heart Association

Heart attack survivors may be slightly less likely to develop Parkinson’s disease later in life, according to new research published in the Journal of the American Heart Association.

Parkinson’s disease (PD) is a common neurodegenerative disorder. While a number of non-motor manifestations arise, the typical clinical features involve a movement disorder consisting of bradykinesia, resting tremor, and rigidity, with postural instability occurring at a later stage. The cause of PD is not known, but a number of genetic risk factors have now been characterised, as well as several genes which cause rare familial forms of PD. Secondary parkinsonism, which has symptoms similar to Parkinson’s disease, may be caused by stroke, psychiatric or cardiovascular medications, or other illness.

“We have previously found that following a heart attack, the risk of neurovascular complications such as ischaemic stroke or vascular dementia is markedly increased, so the finding of a lower risk of Parkinson’s disease was somewhat surprising,” said lead study author Jens Sundbøll, MD, PhD. “These findings indicate that the risk of Parkinson’s disease is at least not increased following a heart attack and should not be a worry for patients or a preventive focus for clinicians at follow-up.

“It is not known whether this inverse relationship with risk of Parkinson’s disease extends to people who have had a heart attack. Therefore, we examined the long-term risk of Parkinson’s disease and secondary parkinsonism among heart attack survivors,” Dr Sundbøll said.

Drawing on Danish National Health Service data, the researchers compared the risk of PD and secondary parkinsonism among roughly 182 000 patients who had a first-time heart attack between 1995 and 2016 (average age 71 years old; 62% male) and more than 909 000 matched controls. 

Over a maximum continual follow-up of 21 years, after adjusting for a wide range of potential confounding factors, the analysis found that, when compared to the control group:

  • there was a 20% lower risk of PD among people who had a heart attack; and
  • a 28% lower risk of secondary parkinsonism among those who had a heart attack.

“For physicians treating patients following a heart attack, these results indicate that cardiac rehabilitation should be focused on preventing ischaemic stroke, vascular dementia and other cardiovascular diseases such as a new heart attack and heart failure, since the risk of Parkinson’s appears to be decreased in these patients, in comparison to the general population,” Dr Sundbøll said.

Certain risk factors are common to both heart attack and PD, with higher risk found among elderly men and lower risk among people who drink more coffee and are more physically active. Interestingly, however, some classic heart attack risk factors – such as smoking, high cholesterol, hypertension and Type 2 diabetes – are associated with a reduced risk of PD.

In general, more heart attack patients smoke and have high cholesterol, either of which may explain the slightly reduced risk of PD among heart attack survivors.

“There are very few diseases in this world in which smoking decreases risk: Parkinson’s disease is one, and ulcerative colitis is another. Smoking increases the risk of the most common diseases including cancer, cardiovascular disease and pulmonary disease and is definitely not good for your health,” Dr Sundbøll noted.

One limitation of the study is that there was not enough information about smoking and high cholesterol levels among the participants, which may have influenced the findings. The study participants were almost entirely white, limiting the generalisability to other ethnic groups.

Source: American Heart Association