Publisher Health

Researchers have developed a human in vitro model that closely mimics the complexities of radiation-induced lung injury (RILI) and radiation dose sensitivity of the human lung. Using a previously developed microfluidic human Lung Alveolus Chip lined by human lung alveolar epithelial cells interfaced with lung capillary cells to recreate the alveolar-capillary interface in vitro, the researchers recapitulated many of the hallmarks of RILI, including radiation-induced DNA damage in lung tissue, cell-specific changes in gene expression, inflammation, and injury to both the lung epithelial cells and blood vessel-lining endothelial cells. By also evaluating the potential of two drugs to suppress the effects of acute RILI, the researchers demonstrated their model’s capabilities as an advanced, human-relevant, preclinical, drug discovery platform.
The lung is one of the tissues most sensitive to radiation in the human body. People exposed to high radiation doses following nuclear incidents develop radiation-induced lung injury (RILI), which affects the function of many cell types in the lung, causing acute and sustained inflammation, and in the longer term, the thickening and scarring of lung tissue known as fibrosis. RILI also is a common side effect of radiation therapy administered to cancer patients to kill malignant cells in their bodies, and can limit the maximum radiation dose doctors can use to control their tumors, as well as dramatically impair patients’ quality of life.
Anti-inflammatory drugs given to patients during radiation therapy can dampen the inflammation in the lungs, called pneumonitis, but not all patients respond equally well. This is because RILI is a complex disorder that varies between patients and is influenced by risk factors, such as age, lung cancer state, and other pre-existing lung diseases, and likely the patient’s genetic makeup. In the event of nuclear accidents, which usually involve the one-time exposure to much higher doses of radiation, no medical countermeasures are available yet that could prevent and protect against the damage to the lungs and other organs, making this a key priority of the US Food and Drug Administration (FDA).
A major obstacle to developing a much deeper understanding of the pathological processes triggered by radiation in the lung and other organs, which is the basis for discovering medical countermeasures, is the lack of experimental model systems that recapitulate how exactly the damage occurs in people. Small animal preclinical models fail to produce key hallmarks of the human pathophysiology and do not mimic the dose sensitivities observed in humans. And although non-human primate models are considered the gold-standard for radiation injury, they are in short supply, costly, and raise serious ethical concerns; they also are not human and sometimes fail to predict responses observed when drugs move into the clinic.
Now, a multi-disciplinary research team at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Boston Children’s Hospital led by Wyss Founding Director Donald Ingber, M.D., Ph.D., in an FDA-funded project, has developed a human in vitro model that closely mimics the complexities of RILI and radiation dose sensitivity of the human lung. Lung alveoli are the small air sacs where oxygen and CO2 exchange between the lung and blood takes place, and the major site of radiation pneumonitis. Using a previously developed microfluidic human Lung Alveolus Chip lined by human lung alveolar epithelial cells interfaced with lung capillary cells to recreate the alveolar-capillary interface in vitro, the researchers recapitulated many of the hallmarks of RILI, including radiation-induced DNA damage in lung tissue, cell-specific changes in gene expression, inflammation, and injury to both the lung epithelial cells and blood vessel-lining endothelial cells. By also evaluating the potential of two drugs to suppress the effects of acute RILI, the researchers demonstrated their model’s capabilities as an advanced, human-relevant, preclinical, drug discovery platform. The findings are published in Nature Communications.
“Forming a better understanding of how radiation injury occurs and finding new strategies to treat and prevent it poses a multifaceted challenge that in the face of nuclear threats and the realities of current cancer therapies needs entirely new solutions,” said Ingber. “The Lung Chip model that we developed to recapitulatedevelopment of RILI leverages our extensive microfluidic Organ Chip culture expertise and, in combination with new analytical and computational drug and biomarker discovery tools, gives us powerful new inroads into this problem.” Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and the Hansjörg Wyss Professor of Bioinspired Engineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.
Advanced human in vitro model of RILI
The human Lung Alveolus Chip is a 2-channel microfluidic culture system in which primary human lung alveolar epithelial cells are cultured in one channel where they are exposed to air as they would be in the lung. They are also interfaced across a porous membrane with primary human lung capillary endothelial cells in the parallel channel that are constantly perfused with a blood-like nutrient medium that contains circulating human immune cells, which also can contribute to radiation responses. This carefully engineered, immunologically active, alveolar-capillary interface also experiences cyclic mechanical movements mimicking actual breathing motions. Importantly, this living breathing Lung Chip can be transiently exposed to clinically relevant doses of radiation, and then investigated for the effects over an extended period of time.

Glioblastoma is the most common type of brain tumor that affects adults and, unfortunately, still remains incurable. In a new study, researchers have demonstrated that a specific mitochondrial protein plays an important role in glioblastoma, and can therefore be used as a potential target to reduce tumors.
“Glioblastoma is notorious for its lethality. One of the major challenges is that it spreads invasively throughout the brain. We’re interested in understanding what drives this process in order to identify new therapeutic strategies,” said Brendan Harley (RBTE leader/EIRH), the Robert W. Schaefer Professor of Chemical and Biomolecular Engineering.
In the current study, the researchers focused on the mitochondrial coiled-coil-helix-coiled-coil-helix domain containing protein 2 — also known as CHCHD2. The complicated name refers to the structure of the protein, whose subunits are coiled together like rope strands.
The researchers first looked at The Cancer Genome Atlas glioblastoma database to see whether they could spot any patterns that related CHCHD2 levels to cancer. Out of 577 samples, they found that the CHCHD2 genes had higher expression in tumor cells, compared to non-tumor tissue, and was higher in advanced cases of glioblastoma.
“We also learned that in humans the gene encoding CHCHD2 was closely linked to the gene encoding the epidermal growth factor receptor, or EGFR, on chromosome 7. A mutated version of this protein is found in over 50% of glioblastoma patients,” said Rex Gaskins (RBTE), the Keith W. and Sara M. Kelley Endowed Professor of Immunophysiology in Animal Sciences and corresponding author of the study.
When the results from the database showed that CHCHD2 expression was highest in the patients who harbored the mutation known as EGFRvIII, the researchers realized that understanding the interaction between these two proteins can be crucial to understanding glioblastoma progression.
To confirm their hypothesis, the researchers looked at the effects of CHCHD2 on tumor growth in mice. They compared mice that had CHCHD2 and the mutated version of EGFR to mice that did not contain CHCHD2, but still had mutated EGFR. The first group of mice survived for an average of 17 days, whereas the second group survived for 25 days. The researchers found that the mice that died earlier had more tumor growth infiltrating the surrounding brain tissue.

Published20 hours agoShareclose panelShare pageCopy linkAbout sharingBy Jim ReedHealth reporterThere was a “lack of urgency” in government as coronavirus started to spread across the UK, a senior scientific adviser has told the Covid public inquiry. Prof Neil Ferguson said he had become “extremely concerned” by 10 March 2020 – two weeks before the first lockdown.Some officials did not understand the data and “did not think it was as bad as it was going to be”, he added. He wrote directly to a Downing Street adviser to try to raise the alarm.The government announced the first UK lockdown on 23 March 2020.Senior officials, including then-Prime Minister Boris Johnson and then-Health Secretary Matt Hancock, will give evidence to the inquiry in December.NHS ‘could be overwhelmed’Prof Ferguson, director of the school of public health at Imperial College London, became a household name in the early stages of the pandemic with his modelling of the spread of Covid and as a member of the expert committee, Sage. Giving evidence to the inquiry on Tuesday, he said he realised by late January 2020 that the government’s early policy of trying to contain the virus would not be possible with the limited border checks and other measures in place at the time. In an email to chief medical officer Sir Chris Whitty on 2 February, he said it was already “quite likely” the virus had been imported into the UK from China. Around the end of February he said he knew that the number of hospital cases was likely to overwhelm the NHS without stronger action to reduce transmission. By 10 March he said he was “extremely concerned” about the latest data. He told the inquiry he had been “frustrated” that some government officials had not “comprehended the figures”.”There was a lack of urgency, let’s put it that way,” he said. He emailed Ben Warner, a data scientist brought in to Downing Street by Dominic Cummings, asking him to make sure the prime minister was shown graphs with projections of between 4,000 and 6,000 deaths a day “under the strategies being considered”. “This event is in the natural-disaster category, and the cure (eg massive social distancing, shutdowns) could be worse than the disease,” he said in the email. Asked why he sent the message, Prof Ferguson said: “It felt uncomfortable, but at the time it felt like it needed to be said. I was increasingly concerned about this disconnect between the numbers we were actually presenting, and the reality of what that would actually look like.”Around that time the government shifted to a mitigation strategy – advising hand-washing and asking people to work from home if possible and self-isolate if they had a fever or cough. Mitigation was designed to slow the rate of infection and spread the number of cases over a longer period of time – or “squash the sombrero” on a graph, as Boris Johnson called it – in an effort to protect the NHS. On 16 March Prof Ferguson and his team published new research suggesting that 250,000 could die without more drastic action.The government started to impose stricter measures around that time. On 16 March the public were asked to stop all non-essential contact and on 18 March schools were closed, before the full lockdown was announced on 23 March. Prof Ferguson, who apologised to the inquiry for breaching Covid rules himself, denied stepping “over the line” as an adviser and telling ministers they needed to shut down the country. “I know I’m very much associated with a particular policy… but the reality was a lot more complex,” he said.”What I tried to do was… focus people’s minds on what was going to happen and the consequences of current trends.”This second stage of the Covid Inquiry is examining political decision-making during the pandemic, including the timing and effectiveness of lockdowns and other social-distancing restrictions. It is taking witness evidence in London until Christmas, before moving to Scotland, Wales and Northern Ireland to look specifically at the decisions made by administrations in those parts of the United Kingdom. More on this storyCovid Inquiry focuses on government as stakes risePublished3 OctoberWhat is the UK Covid inquiry and how long will it take?Published27 September

Adults with attention-deficit/hyperactivity disorder (ADHD) are nearly three times more likely to develop dementia than adults without ADHD, according to a Rutgers study.
The study, coauthored by Michal Schnaider Beeri, director of the Herbert and Jacqueline Krieger Klein Alzheimer’s Research Center at Rutgers Brain Health Institute (BHI) was published in JAMA Network Open. It followed more than 100,000 older adults in Israel over 17 years to examine if adults with ADHD are at increased risk for dementia, including Alzheimer’s disease.
Although more than 3 percent of the adult population in the United States has ADHD, there is limited research on this group.
“By determining if adults with ADHD are at higher risk for dementia and if medications and/or lifestyle changes can affect risks, the outcomes of this research can be used to better inform caregivers and clinicians,” said Beeri, the Krieger Klein Endowed Chair in Neurodegeneration Research at BHI and a faculty member of the Rutgers Institute for Health, Health Care Policy and Aging Research.
Using data from a national cohort study of more than 100,000 people who were followed from 2003 to 2020, researchers analyzed those with and without ADHD and the occurrence of dementia among the groups as they aged. Researchers found the presence of adult ADHD was associated with a significantly higher risk of dementia even when other risk factors for dementia were taken into account, such as cardiovascular conditions.
ADHD in adults may materialize as a neurological process that reduces the ability for them to compensate for the effects of cognitive decline later in life, researchers said.
“Physicians, clinicians and caregivers who work with older adults should monitor ADHD symptoms and associated medications,” said Abraham Reichenberg, a professor at the Department of Psychiatry at the Icahn School of Medicine at Mount Sinai and senior author of the study.
“Symptoms of attention deficit and hyperactivity in old age shouldn’t be ignored and should be discussed with physicians,” said Stephen Levine, a professor at the School of Public Health at the University of Haifa.
Additionally, the research suggests ADHD treatment incorporating psychostimulants may help reduce the risk of dementia in adults with ADHD as psychostimulants are known to modify the trajectory of cognitive impairment. But researchers said future studies should examine in more detail the impact of medications in patients with ADHD and how they could affect risk.
Other coauthors of the study include Anat Rotstein and Galit Weinstein of the University of Haifa; Arad Kodesh of the University of Haifa and Meuhedet Health Services; Sven Sandin of the Department of Psychiatry at the Icahn School of Medicine at Mount Sinai and Karolinska Institutet in Sweden; and Brian Lee of Drexel University.

In certain cases, a new method can provide as much information from brain images taken with computed tomography (CT) as images captured with magnetic resonance imaging (MRI). The method, presented in a study from the University of Gothenburg, could enhance diagnostic support, particularly in primary care, for conditions such as dementia and other brain disorders.
Computed tomography (CT) is a relatively inexpensive imaging technology that is widely available within healthcare, as well as in many parts of the world that lack access to other imaging methods. However, CT is considered inferior to magnetic resonance imaging (MRI) when it comes to reproducing subtle structural changes in the brain or flow changes in the ventricular system. Certain imaging must therefore currently be carried out by specialist departments at larger hospitals where the more advanced imaging technology is available.
AI trained on MRI images
The new software can provide diagnostic support for radiologists and other professionals who interpret CT images. It has been created using deep learning, a form of artificial intelligence (AI). The software has been trained to transfer interpretations from MRI images to CT images of the same brains.
“Our method generates diagnostically useful data from routine CT scans that, in some cases, is as good as an MRI scan performed in specialist healthcare,” says Michael Schöll, a professor at Sahlgrenska Academy who led the work involved in the study, carried out in collaboration with researchers at Karolinska Institutet, the National University of Singapore, and Lund University
“The point is that this simple, quick method can provide much more information from examinations that are already carried out on a routine basis within primary care, but also in certain specialist healthcare investigations. In its initial stage, the method can support dementia diagnosis, however, it is also likely to have other applications within neuroradiology.”
Reliable decision-making support
This is a well-validated clinical application of AI-based algorithms, and has the potential to become a fast and reliable form of decision-making support that effectively reduces the number of false negatives. The researchers believe that this solution can improve diagnostics in primary care and thus optimize patient flow to specialist care.

A new UK study has revealed a significant association between eating disorders and physical multimorbidity, shedding new light on the health risks faced by people with these conditions.
The research, led by Anglia Ruskin University (ARU) in collaboration with the University of Cambridge’s Biomedical Research Centre, explores the complex relationship between eating disorders, physical health, and other issues that can influence it.
Researchers analysed data from 7,403 UK adults. Respondents were asked about 20 physical conditions including cancer, diabetes, eye issues, migraines, digestive problems and heart issues. Influential factors, or mediators, considered included alcohol dependence, insomnia, smoking, perceived stress, obesity and being underweight.
The study found that people with possible eating disorders made up 6.4% of respondents, and individuals within this cohort were 2.11 times more likely to report physical multimorbidity, defined as having two or more physical health conditions concurrently.
An eating disorder is defined as a pathological relationship with food that leads to significant disruptions in a person’s day-to-day life. It is estimated that as many as 3.4 million people in the UK have an eating disorder.
Anxiety emerged as the leading influential factor in the eating disorder and physical multimorbidity relationship. Insomnia, perceived stress, and depression were also identified to be important.
Previous research has shown that multimorbidity is associated with a significant burden on healthcare services including care transition costs and primary care, dental care, and hospitalisations. Multimorbidity affects around 42.4% of the world’s population.
Lead author Lee Smith, Professor of Public Health at Anglia Ruskin University (ARU), said: “We believe this is the first study to investigate the association between eating disorder symptoms, or possible eating disorder, and physical multimorbidity, and also the first to quantify how this association may be explained by a variety of influencing factors.
“This research underscores the complex interplay between mental and physical health. It is essential to recognise that eating disorders can have far-reaching consequences, affecting not only emotional well-being but also physical health. Understanding the role of potential mediators in this relationship is crucial for developing effective interventions.”
The findings hold significant implications for public health, highlighting the need for further investigation into the causality and underlying mechanisms of the link between eating disorders and physical multimorbidity. In the long term, this research could guide the development of strategies to reduce multimorbidity in people with eating disorders by addressing influencing factors.”

Alzheimer’s disease disproportionately affects women, who represent about two-thirds of those diagnosed with the late-onset type of the disease.
Previous research has shown Alzheimer’s is also more severe and progresses more rapidly in women, and women with Alzheimer’s experience a steeper cognitive decline — loss of memory, attention, and the ability to communicate and make decisions — compared to men with the disease.
The biological bases for these differences between men and women with Alzheimer’s disease are not well understood. However, understanding them is necessary for developing appropriate therapies.
In a new study in mice and humans, Western University researchers have shown female sex hormones play a significant role in how Alzheimer’s manifests in the brain.
The study, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, also highlights the importance of developing therapeutic strategies focused on these hormonal connections. The research indicates a need to better understand the role of estradiol — a form of the female sex hormone estrogen, used therapeutically to mitigate menopause symptoms — in Alzheimer’s disease.
While the significance of the findings is paramount, the methodology behind them is equally critical, pointing to a necessary shift in scientific approaches.
“To understand how sex hormones play a role in Alzheimer’s, we need to study appropriate animal models. Unfortunately, most studies at this level still focus mainly on the male brain. Our research emphasizes the importance of using animal models that reflect, for instance, postmenopausal women, to understand how sex hormones influence Alzheimer’s pathology,” said Vania Prado, professor, departments of physiology and pharmacology and anatomy & cell biology at Schulich School of Medicine & Dentistry and scientist at Robarts Research Institute.

In the intricate dance of our body’s defenses against harmful invaders, certain immune system proteins play pivotal roles. New research from the Bridge Institute at the USC Michelson Center for Convergent Bioscience, in collaboration with international teams from India, Australia and Switzerland, has shed light on these proteins.
The work potentially paves the way for innovative treatments for a range of diseases, including severe cases of COVID-19, rheumatoid arthritis, neurodegenerative diseases and cancer.
Central to our immune response is the complement cascade, a series of events activated when potential threats are detected. This process produces protein messengers, C3a and C5a, which in turn activate specific receptors on cells, setting off a cascade of internal signals. The precise mechanisms of these receptors, especially the elusive C5aR1, have remained a mystery.
Using the advanced technique of cryo-electron microscopy (cryo-EM), the researchers captured detailed images of these receptors in action. These images unveil how the receptors interact with molecules, change shape upon activation and transmit signals within the cell.
The study’s lead author, Cornelius Gati, assistant professor of biological sciences, chemistry, and quantitative and computational biology at the USC Dornsife College of Letters, Arts and Sciences, remarked on the findings, noting, “This research offers significant and comprehensive insights into a crucial receptor family within the immune system.”
The study’s revelations suggest potential avenues for the development of drugs targeting these receptors to treat various diseases, added Gati, who heads USC’s cryo-EM facility, which is available for use by researchers around the globe.
As the global community continues to grapple with diseases that impact millions, understanding the nuances of our immune system becomes ever more critical. This research, published in the journal Cell on Oct. 17, contributes to that understanding, providing a foundation for future studies aiming to harness the power of our body’s natural defenses.

Infections with cytomegalovirus (CMV) are extremely common and often pose no major threat to the vast majority of people. They can however be deadly for people whose immune system is weakened, e.g., after bone marrow transplantation. Current treatments against CMV infections are very limited and can have severe side effects. Researchers led by Prof. Michael Sieweke at the Center for Regenerative Therapies Dresden (CRTD) at TUD Dresden University of Technology and the Center of Immunology of Marseille Luminy (CIML) propose a new way to protect against CMV. Instead of targeting the virus, their approach boosts the weak immune system and lets it fight the virus on its own. The results were published in the journal EMBO Molecular Medicine.
Some viruses can be dormant throughout a person’s life and cause no harm but become dangerous when the immune system is weakened. One of such viruses is human cytomegalovirus (CMV). Harmless to the general public but life-threatening to patients with a supressed immune system.
“Patients undergoing bone marrow transplantations have their blood and immune system fully replaced by that of the donor. In the first months after transplantation they are defenseless. They can either catch CMV or have virus reactivated that was dormant in the patient. At the moment, there is no ideal treatment. The available ones work in a limited way or can cause severe side effects such as kidney failure, liver failure, deafness, sepsis, and others,” explains Dr. Julien Subburayalu, a clinical scientist in the Sieweke group at the Center for Regenerative Therapies Dresden (CRTD), one of the leading authors of the study.
The Unusual Approach: Boosting Immune System
Teaming up with Dr. Marc Dalod, an expert on CMV immunity, the researchers led by Prof. Sieweke took an unusual approach. Instead of targeting the virus with antiviral treatments, they focused on strengthening the immune system to fight the virus on its own.
“So far, antiviral treatments focused on targeting specific viruses, either through vaccination or by drugs that work on viral molecular machinery,” mentions Dr. Marc Dalod, group leader at the Centre d’Immunologie de Marseille-Luminy (CIML) and author of the study. “Our method intervenes at the level of patient’s blood stem cells to boosts general antiviral defenses. It’s ideal as a prophylactic or a general intervention strategy in immunosuppressed individuals,” says Prof. Michael Sieweke, Alexander von Humboldt Professor and research group leader at the CRTD and CIML.
Cytokine: Small but Mighty Molecule
The new approach focuses on the cytokine known as macrophage colony-stimulating factor (M-CSF, CSF1). It’s a small signaling molecule that works as a messenger and activator for the immune system. “The cytokine boosts the production of specific white blood cells, mainly monocytes and macrophages,” says Dr. Prashanth Kumar Kandalla, one of the leading authors of the study.

Depression and anxiety among college students is a growing public health problem. And new research from the University of Georgia suggests the problem may be worse for students who aren’t the same race as most of their peers.
The new study found that students who were not the majority race at a predominantly white college reported significantly higher rates of depression than their white peers.
At the mostly white university, more than half of the students who self-identified as races other than white reported feelings of mild depression. An additional 17% said they were experiencing moderate to severe depression.
Students at the predominantly white institution all reported similar levels of anxiety, regardless of race, with more than three in every five students saying they experience mild to severe levels of anxiety.
At the historically Black college, students who weren’t Black experienced higher rates of anxiety and depression as well.
“Our study adds to the evidence of how important the work around inclusivity and mental health is in the college environment,” said Janani Rajbhandari-Thapa, an associate professor in UGA’s College of Public Health. “It’s important to be mindful that not all students come with the same background, and we need to support them more.”
First-generation students more likely to suffer depression
More than 3,100 students participated in the study during the COVID-19 pandemic, answering questions about feelings of hopelessness, sleep issues and lack of energy, among other topics.