Year: 2022

Sound Waves Used to Regrow Bone

Image by Pawel Czerwinski on Unsplash

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?

Source: Pixabay CC0

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

Injectable Nanoparticles That Could Slow Internal Bleeding

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Researchers at MIT have found the ideal size for injectable nanoparticles that could slow traumatic internal bleeding, buying more time for a patient to reach a hospital for further treatment.

In a rat study, the researchers showed that polymer nanoparticles particles in an intermediate size range, (about 150nm in diameter) were the most effective at stopping bleeding. These particles also were much less likely to travel to the lungs or other off-target sites, which larger particles often do. The results were published in ACS Nano.

“With nano systems, there is always some accumulation in the liver and the spleen, but we’d like more of the active system to accumulate at the wound than at these filtration sites in the body,” said senior author Paula Hammond, Professor at MIT.

Nanoparticles that can stop bleeding, also called haemostatic nanoparticles, can be made in a variety of ways. One of the most commonly used strategies is to create nanoparticles made of a biocompatible polymer conjugated with a protein or peptide that attracts platelets, the blood cells that initiate blood clotting.

In this study, the researchers used a polymer known as PEG-PLGA, conjugated with a peptide called GRGDS, to make their particles. Most of the previous studies of polymeric particles to stop bleeding have focused on particles ranging in size from 300–500nm. However, few, if any studies have systematically analysed how size affects the function of the nanoparticles.

“We were really trying to look at how the size of the nanoparticle affects its interactions with the wound, which is an area that hasn’t been explored with the polymer nanoparticles used as haemostats before,” Hong says.

Studies in animals have shown that larger nanoparticles can help to stop bleeding, but those particles also tend to accumulate in the lungs, which can cause unwanted clotting there. In the new study, the MIT team analysed a range of nanoparticles, including small (< 100nm), intermediate (140–220nm), and large (500–650nm).

They first analysed the nanoparticles in the lab to see how how they interacted with platelets in various conditions, to see how well platelets bound to them. They found that, flowing through a tube, the smallest particles bound best to platelets, while the largest particles stuck best to surfaces coated with platelets. However, in terms of the ratio particles to platelets, the intermediate-sized particles were the lowest.

“If you attract a bunch of nanoparticles and they end up blocking platelet binding because they clump onto each other, that is not very useful. We want platelets to come in,” said lead author, Celestine Hong, an MIT graduate student. “When we did that experiment, we found that the intermediate particle size was the one that ended up with the greatest platelet content.”

The researchers injected the different size classes of nanoparticles into mice to see how long they would circulate for, and where they would end up in the body. As with previous studies, the largest nanoparticles tended accumulated in the lungs or other off-target sites.

The researchers then used a rat model of internal injury to study which particles would be most effective at stopping bleeding. They found that the intermediate-sized particles appeared to work the best, and that those particles also showed the greatest accumulation rate at the wound site.

“This study suggests that the bigger nanoparticles are not necessarily the system that we want to focus on, and I think that was not clear from the previous work. Being able to turn our attention to this medium-size range can open up some new doors,” Prof Hammond said.

The researchers now hope to test these intermediate-sized particles in larger animal models, to get more information on their safety and the most effective doses. They hope that eventually, such particles could be used as a first line of treatment to stop bleeding from traumatic injuries long enough for a patient to reach the hospital.

Source: Massachusetts Institute of Technology

Vegetable Intake Does Not Reduce Cardiovascular Risk, Study Finds

Photo by Daria Shevtsova from Pexels

A long-term study on almost 400 000 people in the UK finds little or no evidence that differences in the amount of vegetables consumed affects the risk of cardiovascular disease. 

When known socio-economic and lifestyle confounding factors are corrected for, the small apparent positive effect that remains could likely also be explained away by further confounders.

Getting enough vegetables is important for maintaining a balanced diet and avoiding a wide range of diseases. But might a diet rich in vegetables also lower the risk of cardiovascular disease (CVD)? Unfortunately, new results from a powerful, large-scale new study study in Frontiers in Nutrition found no evidence for this.

The notion of CVD risk being lowered by vegetable consumption might seem plausible at first, as their ingredients such as carotenoids and alpha-tocopherol (vitamin E) have properties that could protect against CVD. But so far, prior evidence for an overall effect of vegetable consumption on CVD has been inconsistent.

The study, which drew on UK Biobank data, found a higher consumption of cooked or uncooked vegetables is unlikely to affect the risk of CVD. The study authors also explained how confounding factors might explain previous spurious, positive findings.

“The UK Biobank is a large-scale prospective study on how genetics and environment contribute to the development of the most common and life-threatening diseases. Here we make use of the UK Biobank’s large sample size, long-term follow-up, and detailed information on social and lifestyle factors, to assess reliably the association of vegetable intake with the risk of subsequent CVD,” said Prof Naomi Allen, UK Biobank’s chief scientist and co-author on the study.

The UK Biobank, follows the health of half a million adults in the UK by linking to their healthcare records. Upon their enrolment in 2006-2010, these volunteers were  interviewed about their diet, lifestyle, medical and reproductive history, and other factors.

The researchers used the responses at enrolment of 399 586 participants (of whom 4.5% went on to develop CVD) to questions about their daily average consumption of uncooked versus cooked vegetables. They analysed the association with the risk of hospitalization or death from myocardial infarction, stroke, or major CVD. They controlled for a wide range of possible confounding factors, including socio-economic status, physical activity, and other dietary factors.

Crucially, the researchers also assessed the potential role of ‘residual confounding’, that is, whether unknown additional factors or inaccurate measurement of known factors might lead to a spurious statistical association between CVD risk and vegetable consumption.

The mean daily intake of total vegetables, raw vegetables, and cooked vegetables was 5.0, 2.3, and 2.8 heaped tablespoons per person. The risk of dying from CVD was about 15% lower for those with the highest intake compared to the lowest vegetable intake. However, this effect was greatly weakened when possible confounding factors were taken into account. Controlling for factors such as socio-economic status reduced the predictive statistical power of vegetable intake on CVD by over 80%, suggesting that more precise measures of these confounders would have explained away any residual effect of vegetable intake.

Dr Qi Feng, the study’s lead author, said: “Our large study did not find evidence for a protective effect of vegetable intake on the occurrence of CVD. Instead, our analyses show that the seemingly protective effect of vegetable intake against CVD risk is very likely to be accounted for by bias from residual confounding factors, related to differences in socioeconomic situation and lifestyle.”

The researchers suggest that subsequent studies should further assess whether particular types of vegetables or their method of preparation might affect the risk of CVD.

Source: Frontiers

No Difference Between Paramedics’ Advanced Airway Management Strategies

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Similar outcomes were seen for patients with out-of-hospital cardiac arrest (OHCA) regardless of the advanced airway management strategy used by paramedics, results from the Taiwanese SAVE trial showed.

There was no generally no difference in clinical outcomes between groups that had the initial strategies of endotracheal intubation or supraglottic airway device insertion:

Sustained return of spontaneous circulation (ROSC) two hours after resuscitation: 26.9% vs 25.8%; survival to hospital discharge: 8.5% vs 8.4%; cerebral performance category score ≤ 2: 3.9% vs 4.8%.

Only prehospital ROSC suggested an advantage to standard endotracheal intubation (10.6% vs 6.4%), according to the researchers, whose study was published in JAMA Network Open.

Endotracheal intubation is a difficult procedure to get right. The SAVE paramedics, all experienced in both methods of advanced airway management, employed direct laryngoscopy and achieved a 77% rate of first-attempt airway success with endotracheal intubation (vs 83% with the supraglottic device). Average scene time (18.4 vs 16.9 minutes) and call-to-airway time (15.9 vs 13.9 minutes) were both longer with endotracheal intubation.

“It is unclear whether a stepwise and algorithmic endotracheal intubation training program could reduce the time in the field and the time for advanced airway insertion, and further research is warranted,” the authors said.

For the SAVE trial conducted from 2016 to 2019, researchers randomly split four EMS teams in Taipei into two clusters, each assigned to initial endotracheal intubation or supraglottic i-gel device insertion when responding to OHCAs over a biweekly period. In case the first advanced airway attempt failed, rescue airway management was allowed using a number of techniques.

The 936 OHCA patients in the study had a median age of 77 years, and 60.8% were men.

However, subgroup analysis showed that prehospital ROSC rates favoured endotracheal intubation in patients with nonshockable rhythm, nonpublic collapse, witnessed arrest, call-to-airway time under 14 minutes, and age 77 years or older.

However, different in-hospital management between groups could have affected the results. The two study arms were unequal in size, and the study could have been underpowered because of inaccurate sample size representation at the study outset. However, the researchers lamented that “even if we had realised that the sample size was inadequate at that time, we would not have been able to recruit more cases because of the outbreak of COVID.”

Source: MedPage Today

Political Factors Drove Hydroxychloroquine and Ivermectin COVID Prescriptions

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Hydroxychloroquine and ivermectin, two COVID treatments that have been shown to be ineffective for those purposes, were more heavily prescribed in the second half of 2020 in parts of the US that voted for the Republican party, according to a new research letter published in JAMA Internal Medicine.

“We’d all like to think of the health care system as basically non-partisan, but the COVID pandemic may have started to chip away at this assumption,” said lead author Michael Barnett, assistant professor of health policy and management.

The study compared prescription rates for hydroxychloroquine and ivermectin with rates for two control medications, methotrexate sodium and albendazole, which are similar drugs but have not been proposed as COVID treatments. Comparing different US counties, researchers looked at deidentified medical claims data from January 2019 through December 2020 from roughly 18.5 million adults as well as census and voting data.

Overall, hydroxychloroquine prescribing volume from June through December 2020 was roughly double what it had been in the previous year, while the volume of ivermectin prescriptions was seven-fold higher in December 2020 than the previous year. In 2019, prescribing of hydroxychloroquine and ivermectin did not differ according to county Republican vote share. However, that changed in 2020.

After June 2020 – coinciding with when the US Food and Drug Administration revoked emergency use authorisation for hydroxychloroquine – prescribing volume for the drug was significantly higher in counties with the highest Republican vote share as compared to counties with the lowest vote share.

As for ivermectin, prescribing volume was significantly higher in the highest versus lowest Republican vote share counties in December 2020 a 964% increase on the overall prescribing volume in 2019. The spike lined up with with a number of key events, such as the mid-November 2020 release of a now-retracted manuscript claiming that the drug was highly effective against COVID, and a widely publicised US Senate hearing in early December that included testimony from a doctor promoting ivermectin as a COVID treatment.

Neither of the control drugs had differences in overall prescribing volume or in prescribing by county Republican vote share.

The authors concluded that the prescribing of hydroxychloroquine and ivermectin may have been influenced by physician or patient political affiliation. “This is the first evidence, to our knowledge, of such a political divide for a basic clinical decision like infection treatment or prevention,” said Barnett.

Source: Harvard T.H. Chan School of Public Health

Endocrine-disrupting Chemicals Present in Many Pregnancies

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Researchers in Europe have shown that up to 54% of pregnant women in Sweden were exposed to complex mixtures of endocrine-disrupting chemicals disruptive to brain development.

While current risk assessment tackles chemicals and their allowable exposures on an individual basis, these findings show the need to take mixtures into account for future risk assessment approaches. The study was published in Science.

A growing body of evidence has shown that industrially produced chemicals have endocrine disrupting properties and can thus be dangerous to human and animal health and development. A huge number of new compounds is released every year into the environment during the production of plastic derivatives and other goods.

While exposures for individual chemicals falls below thresholds, exposure to the same chemicals in complex mixtures can still impact human health. However, all current exposure thresholds, are based on chemicals being examined individually. Therefore, an alternative strategy needed to be tested, in which the actual mixtures measured in real life exposures could be tested as such in both the epidemiological and experimental setting. The EDC-MixRisk project set out to tackle this unmet need.

“The uniqueness of this comprehensive project is that we have linked population data with experimental studies, and then used this information to develop new methods for risk assessment of chemical mixtures,” said Carl-Gustaf Bornehag, professor at Karlstad University, Project Manager of the SELMA study.

The study was conducted in three steps:

  1. A mixture of chemicals in the blood and urine of pregnant women was identified in the Swedish pregnancy cohort SELMA, associated with delayed language development in children at 30 months. This critical mixture included a number of phthalates, bisphenol A, and perfluorinated chemicals.
  2. Experimental studies uncovered the molecular targets through which human-relevant levels of this mixture disrupted the regulation of endocrine circuits and of genes involved in autism and intellectual disability.
  3. The findings from the experimental studies were used to develop new principles for risk assessment of this mixture.

“It is striking that the findings in the experimental systems well reflected what we found in the epidemiological part, and that the effects could be demonstrated at normal exposure levels for humans,” said Joëlle Rüegg, professor of environmental toxicology at Uppsala University.

“Human brain organoids (advanced in vitro cultures that reproduce salient aspects of human brain development) afforded, for the first time, the opportunity to directly probe the molecular effects of this mixture on human brain tissue at stages matching those measured during pregnancy. Alongside other experimental systems and computational methods, we found that the mixture disrupts the regulation of genes linked to autism (one of whose hallmarks is language impairment), hinders the differentiation of neurons and alters thyroid hormone function in neural tissue,” said Giuseppe Testa, principal investigator of the EDC-MixRisk responsible for the human experimental modelling.

“One of the key hormonal pathways affected was thyroid hormone. Optimal levels of maternal thyroid hormone are needed in early pregnancy for brain growth and development, so it’s not surprising that there is an association with language delay as a function of prenatal exposure,” said Barbara Demeneix, professor of physiology and endocrinology at the Natural History Museum in Paris.

By combining these techniques, the researchers were able to show that 54% of children included in the SELMA study were at risk of delayed language development (at age 30 months) as they were prenatally exposed to a mixture of chemicals at levels that were above the levels predicted to impact neurodevelopment. Yet this risk fell below the exposure limits for individual chemicals.

Source: EURION Cluster