In a study published in the journal PNAS, a research team led by the University of Minnesota Medical School have shown that the socioeconomic status (SES) of cell donors affects the health outcomes of blood cancer patients who underwent haematopoietic cell transplantation (HCT).
The study examined the health outcomes of 2005 blood cancer patients treated with HCT in the United States. The research team found cancer patients who were transplanted with cells from donors of greatest socioeconomic disadvantage experienced a 9.7% reduction in overall survival and 6.6% increase in transplant-related mortality at three years compared to those transplanted from donors of high socioeconomic status – regardless of the cancer patient’s socioeconomic status.
“Our findings are quite remarkable. We have shown that social disadvantage penetrates so deeply that it is actually transplantable into a new host, and its effects persist over time,” said Lucie Turcotte, MD, MPH, MS, an associate professor at the University of Minnesota Medical School.
The results show the striking biological impact of social disadvantage and how it can alter health outcomes, specifically in the setting of cancer and hematopoietic cell transplantation.
The research team plans to conduct further research to investigate the underlying biological and physiologic drivers of these findings in order to develop interventions to mitigate the adverse health outcomes introduced by socioeconomic disadvantage.
“The importance of these findings reach far beyond cancer and bone marrow transplant care – they demonstrate the profound health effects of social inequality and highlight the critical need for public health interventions,” said Dr Turcotte.
A world-first study has found low-dose aspirin may treat flu-induced blood vessel inflammation, creating better blood flow to the placenta during pregnancy. Animal studies examined whether the treatment for preeclampsia could be applied to flu infections – and the results, published in Frontiers in Immunology, were very promising.
Lead researcher and RMIT Post-Doctoral Research Fellow, Dr Stella Liong, said that flu infections during pregnancy can resemble preeclampsia, a pregnancy complication that causes inflammation to the aorta and blood vessels. Low-dose aspirin is commonly taken to prevent preeclampsia, as it stops the body from creating chemicals that cause inflammation.
“When the vascular system is inflamed, it leads to poor blood flow and affects the aorta’s function,” she said. “This is especially a problem during pregnancy where good blood flow to the placenta is crucial to the development of the foetus.”
The research, led by RMIT University in collaboration with Trinity College Dublin, Ireland Professor John O’Leary and University of South Australia Professor Doug Brooks, found foetuses and placenta from mice with influenza A were smaller than those from uninfected mice.
Markers of low blood oxygenation and poor blood vessel development were also evident in the foetuses. The mice treated daily with low-dose aspirin had less inflammation and improved foetal development and offspring survival.
While the research was still awaiting human clinical trials, Liong said low-dose aspirin was already recognised as safe to take during pregnancy. The research team however recommended pregnant people seek medical advice before taking new medications.
Brooks said influenza A infections during pregnancy was a big concern as every pregnancy overlaps with part of a flu season.
“There are long term implications for both the mother and the foetus, and aspirin might provide a simple solution for preventing this influenza associated pathology,” Brooks said.
Why flu infection is dangerous during pregnancy
O’Leary said the research findings had huge implications for pregnancy and seasonal influenza virus infections for pregnant people.
“This study shines a light, for the first time, on the role of vascular inflammation associated with influenza virus and the potential dramatic effect of the disease-modifying drug aspirin, in low dosage, in pregnant women with co-morbid influenza,” O’Leary said.
While there weren’t many studies of the impacts of flu infections during pregnancy, project lead and RMIT Professor Stavros Selemidis said it was clear that pregnancy changed how the body responded to the virus.
Liong and Selemidis’ earlier breakthrough research found the flu virus during pregnancy could trigger a damaging hyperactive immune response, causing the virus to spread around the body from the lungs through the blood vessels.
“We used to think the flu virus just stayed in the lungs, but during pregnancy it escapes from the lungs to the rest of the body,” Selemidis said.
“This infection could set you up for cardiovascular disease later in life, but also set up cardiovascular disease in the offspring later in life.”
While vaccination was still the considered the best way to prevent flu infection during pregnancy, Selemidis pointed out vaccination rates were generally low in the pregnant population.
“Low vaccination rates aside, the flu shot may not generate the perfect immune response, especially if someone is pregnant or has an underlying medical condition,” he said.
“That’s why it’s useful to have a potential back up in low-dose aspirin to help prevent vascular dysfunction during pregnancy and improve foetal development.”
Targeting oligodendrocytes could help reduce amyloid beta production
Neurons in the brain of an Alzheimer’s patient, with plaques caused by tau proteins. Credit: NIH
Oligodendrocytes are an important source of amyloid beta (Aβ) and play a key role in promoting neuronal dysfunction in Alzheimer’s disease (AD), according to a study published July 23, 2024 in the open-access journal PLOS Biology by Rikesh Rajani and Marc Aurel Busche from the UK Dementia Research Institute at University College London, and colleagues.
AD is a devastating neurodegenerative disorder affecting millions of people worldwide. Accumulation of Aβ – peptides consisting of 36 to 43 amino acids – is an early critical hallmark of the disease. Recent clinical trials demonstrating a slowing of cognitive and functional decline in individuals with AD who are treated with anti-Aβ antibodies reinforce the important role of Aβ in the disease process. Despite the key cellular effects of Aβ and its essential role in AD, the traditional assumption that neurons are the primary source of toxic Aβ in the brain has remained untested.
In the study, Rajani and Busche showed that non-neuronal brain cells called oligodendrocytes produce Aβ. They further demonstrated that selectively suppressing Aβ production in oligodendrocytes in an AD mouse model is sufficient to rescue abnormal neuronal hyperactivity. The results provide evidence for a critical role of oligodendrocyte-derived Aβ for early neuronal dysfunction in AD. Collectively, the findings suggest that targeting oligodendrocyte Aβ production could be a promising therapeutic strategy for treating AD.
According to the authors, the functional rescue is remarkable given the relatively modest reduction in plaque load that results from blocking oligodendrocyte Aβ production, while blocking neuronal Aβ production leads to a near elimination of plaques – another hallmark of the disease. This small contribution of oligodendrocytes to plaque load could suggest that a main effect of oligodendrocyte-derived Aβ is to promote neuronal dysfunction.
Together with the data showing an increased number of Aβ-producing oligodendrocytes in deeper cortical layers of the brains of individuals with AD, these results indicate that oligodendrocyte-derived Aβ plays a pivotal role in the early impairment of neuronal circuits in AD, which has important implications for how the disease progresses and is treated. The increased number of oligodendrocytes in human AD brains also raises the intriguing possibility that these cells could potentially offset reduced Aβ production due to neuronal loss as the disease progresses.
The authors add, “Our study challenges the long-held belief that neurons are the exclusive source of amyloid beta in the brain, one of the key toxic proteins that builds up in Alzheimer’s Disease. In fact, we show that oligodendrocytes, the myelinating cells of the central nervous system, can also produce significant amounts of amyloid beta which impairs neuronal function, and suggests that targeting these cells may be a promising new strategy to treat Alzheimer’s Disease.”
Study analyzed 7 major health themes across 185 countries before and after the COVID-19 pandemic
The COVID-19 pandemic significantly widened existing economic and health disparities between wealthy and low-income countries and slowed progress toward health-related Sustainable Development Goals (SDGs), according to a new study published July 24, 2024, in the open-access journal PLOS ONE by Wanessa Miranda of Federal University of Minas Gerais, Brazil, and colleagues.
The global SDGs were established in 2015 as a wide and integrated agenda with themes ranging from eradicating poverty and promoting well-being to addressing socioeconomic inequalities. However, the COVID-19 pandemic is known to have delivered a devastating blow to global health, with large economic repercussions.
The new study investigated the potential impact of these economic disruptions on progress toward health-related SDGs. The research team used data from the official United Nations SDG database and analysed the associations between well-being, income levels, and other key socioeconomic health determinants. A yearly model was extrapolated to predict trends between 2020 and 2030 using a baseline projection as well as a post-COVID-19 scenario.
The study estimated average economic growth losses in the wake of the COVID-19 pandemic as 42% and 28% for low and lower middle-income countries and 15% and 7% in high- and upper middle-income countries. These economic disparities are projected to drive global health inequalities in the themes of infectious disease, injuries and violence, maternal and reproductive health, health systems coverage and neonatal and infant health. Overall, low-income countries can expect an average progress loss of 16.5% across all health indicators, whereas high-income countries can expect losses as low as 3%. Individual countries, such as Turkmenistan and Myanmar, have estimated a loss of progress which is as much as nine times worse than the average loss of 8%. The most significant losses are seen in Africa, the Middle East, Southern Asia, and Latin America.
The authors conclude that the impact of the pandemic has been highly uneven across global economies and led to heightened inequalities globally, particularly impacting the health-related targets of the 2030 SDG Agenda.
The authors add: “The COVID-19 pandemic significantly widened existing economic and health disparities between wealthy and low-income countries and slowed progress toward health-related Sustainable Development Goals (SDGs). Overall, low-income countries can expect an average progress loss of 16.5% across all health indicators, whereas high-income countries can expect losses as low as 3%.”
