A mysterious outbreak of bone-eating tb resembled an ancestral form

Tuberculosis is usually encountered as a disease of the lungs, but in 2 percent of cases in the U.S. it can also be found in the bones. The 9,000-year-old skeletons of some Egyptian mummies show signs of having tuberculosis infection in their bones, a painful condition that leaves the bones looking like they’ve been gnawed.

So, it was a weird puzzle when Duke physician Jason Stout M.D. encountered a Wake County TB outbreak in the mid-2000s in which the infection had spread beyond the lungs in six people. “Four out of six were in the bone,” Stout said. “That’s way more than 2 percent.”

The index case, the first person in Raleigh to have this strain of the disease, apparently contracted the bacterium in Vietnam, but he wasn’t feeling very sick and had been working around 400 people in his workplace.

“So, it was prolonged exposure in a workplace,” said Stout, a Duke professor of medicine who tracked down and identified seven subsequent infections through contact tracing and health department records.

All eight people were treated with antibiotics and other co-workers received preventative care and then the strange outbreak went away. But the mystery was never really solved. “I’m an epidemiologist and clinical trial specialist and I was left scratching my head,” Stout said.

Screening for stroke risk can save lives and money

Emma Svennberg, specialist in cardiology. Screening involves placing the thumbs onto a hand-held ECG machine.
Photo Credit: Johan Adelgren

Atrial fibrillation is the greatest risk factor for stroke. Screening to detect atrial fibrillation in older people would not only increase the chance of preventing stroke, it would also save money for the healthcare system and society. This is the conclusion from research conducted at Linköping University and Karolinska Institutet.

“The greatest benefit from screening is that you receive information that could be used to reduce an individual’s risk of stroke and thus may help them live longer with a good quality of life,” says Emma Svennberg, specialist in cardiology at Karolinska University Hospital, and affiliated researcher at Karolinska Institutet.

A systematic screening program for atrial fibrillation is not in use anywhere in the world. The researchers who conducted the present study, published in European Journal of Heart, have calculated the cost effectiveness of screening for atrial fibrillation in people aged 75-76 years, and conclude that there are strong reasons for introducing such a program.

A new nanoparticle to act at the heart of cells

This electron micrograph documents the porous nature of silica nanoparticles. These pores are large enough to allow entrance of a large number of NSA molecules. Here, they are protected until being taken up by the immune cells. At this point NSA is released and can stop the inflammatory processes.
Credit: UNIGE - Carole Bourquin

How can a drug be delivered exactly where it is needed, while limiting the risk of side effects? The use of nanoparticles to encapsulate a drug to protect it and the body until it reaches its point of action is being increasingly studied. However, this requires identifying the right nanoparticle for each drug according to a series of precise parameters. A team from the University of Geneva (UNIGE) and the Ludwig Maximilians Universität München (LMU) has succeeded in developing a fully biodegradable nanoparticle capable of delivering a new anti-inflammatory drug directly into macrophages - the cells where uncontrolled inflammatory reactions are triggered - ensuring its effectiveness. In addition, the scientists used an invitro screening methodology, thus limiting the need for animal testing. These results, recently published in the Journal of Controlled Release, open the way to an extremely powerful and targeted anti-inflammatory treatment.

Inflammation is an essential physiological response of the body to defend itself against pathogens such as bacteria. It can, however, become problematic when it turns into a chronic condition, such as in cancers, autoimmune diseases or certain viral infections. Many treatments already exist, but their action is often not very targeted, high doses are required and deleterious side effects are frequent. Macrophages, large immune cells whose natural function is to absorb pathogens and trigger inflammation to destroy them, are often involved in inflammatory diseases. When overactivated, they trigger an excessive inflammatory response that turns against the body instead of protecting it.

Low levels of air pollution deadlier than previously thought

Photo Credit: Ralf Vetterle

The World Health Organization’s most recent estimates (2016) are that over 4.2 million people die prematurely each year due to long-term exposure to fine particulate outdoor air pollution (often referred to as PM2.5,). A recent study involving McGill researchers now suggests that the annual global death toll from outdoor PM2.5 may be significantly higher than previously thought. That’s because the researchers found that mortality risk was increased even at very low levels of outdoor PM2.5, ones which had not previously been recognized as being potentially deadly. These microscopic toxins cause a range of cardiovascular and respiratory diseases and cancers.

“We found that outdoor PM2.5 may be responsible for as many as 1.5 million additional deaths around the globe each year because of effects at very-low concentrations that were not previously appreciated,” said Scott Weichenthal, an Associate Professor in the Department of Epidemiology, Biostatistics, and Occupational Health at McGill University and the lead author on the recent paper in Science Advances.

UQ study explains link between sleep apnea and dementia

Professor Elizabeth Coulson said the findings suggest CPAP treatment of obstructive sleep apnea has the potential to reduce dementia risk.
Credit: University of Queensland

Researchers at The University of Queensland have discovered a link between obstructive sleep apnea and an increased risk of developing dementia.

Professor Elizabeth Coulson from UQ’s Queensland Brain Institute and School of Biomedical Sciences and her team found a causal relationship between a lack of oxygen to the brain during sleep and Alzheimer’s disease in mice.

“We found sleep deprivation alone in mice caused only mild cognitive impairment,” Professor Coulson said.

“But we developed a novel way to induce sleep-disrupted breathing and found the mice displayed exacerbated pathological features of Alzheimer’s disease.

“It demonstrated that hypoxia – when the brain is deprived of oxygen – caused the same selective degeneration of neurons that characteristically die in dementia.”

Professor Coulson said the next step would be to determine what levels of hypoxia result in brain degeneration in humans.

New experimental treatment can stop the growth of schwannoma tumors

Researchers showed that after just 21 days of the drugs being administered, tumor growth can be strongly and significantly reduced.
Photo Credit: MART PRODUCTION

Two novel and orally administered drugs can not only block the growth, but also shrink the size, of a tumor type found in the nervous system, new research has shown.

The tumors, schwannomas, most frequently grow on the nerves that bring hearing and balance information into the brain. Schwannomas are the most common nerve sheath tumor, and can occur in anyone but are also linked to a hereditary condition known as Neurofibromatosis Type II (NF2).

In NF2, where the function of the protein Merlin is lost in cells, patients frequently develop not only schwannomas, but also meningioma tumors associated with the brain and spinal cord.

The treatment of both tumor types is difficult, with surgery being the current mainstay but also carrying a high risk of damage to the surrounding normal nervous system tissue.

With an urgent need for new treatments, an international team of scientists focused on the Hippo signaling pathway, which normally controls organ size in human tissues and cells, but is dysregulated in multiple types of cancer.

An easier way to remove medical devices

MIT engineers have shown that medical devices made from aluminum can be disintegrated within the body by exposing them to gallium-indium, a liquid metal that seeps into the boundaries between the grains of the metal.
Credit: MIT based on figures courtesy of the researchers

By taking advantage of a phenomenon that leads to fractures in metal, MIT researchers have designed medical devices that could be used inside the body as stents, staples, or drug depots, then safely broken down on demand when they’re no longer needed.

The researchers showed that biomedical devices made from aluminum can be disintegrated by exposing them to a liquid metal known as eutectic gallium-indium (EGaIn). In practice, this might work by painting the liquid onto staples used to hold skin together, for example, or by administering EGaIn microparticles to patients.

Triggering the disintegration of such devices this way could eliminate the need for surgical or endoscopic procedures to remove them, the researchers say.

“It’s a really dramatic phenomenon that can be applied to several settings,” says Giovanni Traverso, the Karl van Tassel Career Development Assistant Professor of Mechanical Engineering at MIT and a gastroenterologist at Brigham and Women’s Hospital. “What this enables, potentially, is the ability to have systems that don’t require an intervention such as an endoscopy or surgical procedure for removal of devices.”

Traverso is the senior author of the study, which appears in Advanced Materials. Vivian Feig, an MIT postdoc, is the lead author of the paper.

University of Oxford study provides important insights into TB correlates of protection

Drug-resistant, Mycobacterium tuberculosis bacteria, the pathogen responsible for causing the disease tuberculosis (TB). A 3D computer-generated image.
Image Credit: CDC

Researchers from the University of Oxford have today reported findings from a study that investigated whether previously identified correlates of protection associated with risk of full-blown tuberculosis (TB) disease could also be associated with risk of infection from the bacteria that causes TB - highlighting certain correlates in the process.

In their paper on the TB020 study, published in Nature Communications, researchers identified that certain correlates of protection – inflammation and activation of the immune system (where the body responds to invading pathogens such as viruses and harmful bacteria) – were associated with the likelihood of becoming infected with Mycobacterium tuberculosis (M.tb), the bacteria that causes TB disease.

However, their previously identified correlates of risk of TB disease were not associated with an increased risk of M.tb infection in infants who became infected with the bacteria but did not progress to active TB.

Most individuals infected with M.tb do not progress to full TB disease. Instead, infection is either eliminated or contained by the infected individual. This study improves understanding of the immune-related factors that drive infection and disease – necessary for an effective TB vaccine that is yet to be developed.

First ever clinical trial underway of laboratory grown red blood cells being transfused into another person

Microscope image Example of a RESTORE laboratory grown young red blood cell
Image Credit: NHS Blood and Transplant

The manufactured blood cells were grown from stem cells from donors. The red cells were then transfused into volunteers in the RESTORE randomized controlled clinical trial.

This is the first time in the world that red blood cells that have been grown in a laboratory have been given to another person as part of a trial into blood transfusion.

If proved safe and effective, manufactured blood cells could in time revolutionize treatments for people with blood disorders such as sickle cell and rare blood types. It can be difficult to find enough well-matched donated blood for some people with these disorders.

Chief Investigator Professor Cedric Ghevaert, Professor in Transfusion Medicine and Consultant Haematologist at the University of Cambridge and NHS Blood and Transplant, said: “We hope our lab grown red blood cells will last longer than those that come from blood donors. If our trial, the first such in the world, is successful, it will mean that patients who currently require regular long-term blood transfusions will need fewer transfusions in future, helping transform their care.”

The RESTORE trial is a joint research initiative by NHS Blood and Transplant and the University of Bristol, working with the University of Cambridge, Guy’s and St Thomas’ NHS Foundation Trust, NIHR Cambridge Clinical Research Facility, and Cambridge University Hospitals NHS Foundation Trust. It is part-funded by a National Institute for Health and Care Research (NIHR) grant.

Researchers identify protein linked to heart failure in chemo patients: Finding could save millions of lives

Dr. Lorrie Kirshenbaum from the Rady Faculty of Health Sciences
Source: University of Manitoba

A team led by Dr. Lorrie Kirshenbaum from the Rady Faculty of Health Sciences and St. Boniface Hospital Research has identified a protein called TRAF2 that stops functioning in cancer patients taking the chemotherapy drug doxorubicin, which can result in heart failure.

“The finding could lead to new drugs that save cancer patients,” said Kirshenbaum, lead investigator and UM Canada Research Chair in molecular cardiology and director of the Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre.

While doxorubicin is used to treat many types of cancer, particularly breast and ovarian cancer, some patients who receive the drug develop heart problems that lead to heart failure.

Using a variety of state-of-the-art approaches, the researchers discovered that doxorubicin impairs the activity of TRAF2 in the heart which leads to heart failure. The team also showed that interventions that restored the TRAF2 activity suppressed the unwanted side effects and heart failure induced by doxorubicin treatment.

“This is a significant finding that we are very excited about,” said Kirshenbaum, professor of physiology & pathophysiology and pharmacology & therapeutics, Max Rady College of Medicine, University of Manitoba. “We discovered that TRAF2 was consistently down-regulated in cancer patients with heart failure who had received doxorubicin treatment. Our pre-clinical study showed that by restoring TRAF2, we could prevent injury to the heart muscle and heart failure induced by doxorubicin.”

Substance use disorders linked to poor health outcomes in wide range of physical health conditions

Photo Credit: Concord90

In a study published today in The Lancet Psychiatry, researchers looked at the risk of mortality and loss of life-years among people who developed 28 different physical health conditions, comparing those who had previously been hospitalized with substance use disorder against those who had not.

They found that patients with the most health conditions were more likely than their counterparts to die during the study period if they had been hospitalized with substance use disorder prior to the development of these conditions. For most subsequent health conditions, people with substance use disorders also had shorter life-expectancies than did individuals without substance use disorders.

One in twenty people worldwide aged 15 years or older lives with alcohol use disorder, while around one in 100 people have psychoactive drug use disorders. Although substance use disorders have considerable direct effects on health, they are also linked to a number of physical and mental health conditions. Consequently, the presence of these contributes to higher risk of mortality and shorter lifespan in people with substance use disorders.

To explore this link further, researchers analyzed patient records from Czech nationwide registers of all-cause hospitalizations and deaths during the period from 1994-2017. They used a novel design, estimating the risk of death and life-years lost after the onset of multiple specific physical health conditions in individuals with a history of hospitalization for substance use disorders, when compared with matched counterparts without substance use disorder but with the same physical health condition.

Characterizing the ‘Noisy Life of a Musician’: Risks and Benefits for Brain Aging

Skoe's study will gather information about participants' noise environments, both while playing music and doing other daily activities.
Credit: Pixabay

As a child growing up in Germany, Erika Skoe taught herself to play German songs on the piano before she was comfortable speaking the language. Skoe, now an associate professor of speech, language, and hearing sciences at UConn and self-described lapsed musician has made a career studying hearing and brain function in people young to old, with a special focus on language and music.

Previous research has shown that regular exposure to noise may accelerate brain aging. But other work shows older musicians’ brain and cognitive function resembles that of somebody much younger. To Skoe, these independent lines of research seemed at odds: if noise exposure is harmful to the brain, why are older musicians neurologically sharper than non-musicians, given that musicians are at higher risk of experiencing dangerous noise levels?

In a new $1.6 million grant from the National Institutes of Health, titled “The Noisy Life of the Musician: Implications for Healthy Brain Aging,” Skoe will lead an effort to reconcile the health benefits and hazards of being a musician and their interplay as people age. This study was funded through the NIH Sound Health initiative, a program supporting research on health applications of music.

The unintended consequences of using a ventilator

Higher strains caused by artificial ventilators (left) and less stretch when the same lung is made to breathe naturally.
Photo Credit: Mona Eskandari/UCR

Breakthrough research addresses a long-standing question in pulmonary medicine about whether modern ventilators overstretch lung tissue. They do.

These cutting-edge findings by UC Riverside researchers were recently published in the American Journal of Respiratory and Critical Care Medicine. They demonstrate major differences between how we naturally breathe versus how ventilators make us breathe. These results are critical, particularly in context of the COVID-19 pandemic and the rush to build ventilators.

“Using novel techniques, we observed that ventilators can overextend certain regions of the lungs,” said Mona Eskandari, UCR assistant professor of mechanical engineering and the BREATHE Center in the School of Medicine, who led the research. These results provide an explanation for the decline in lung health experienced by patients the longer they spend on the machines, especially in the case of disease.

Eskandari’s bMECH lab pioneered a technique to study lungs as they are made to breathe. On a custom-built ventilator designed in their lab, the researchers imitated both natural and artificial breathing. Then, they observed isolated lungs involved in both types of breathing using multiple cameras collecting fast, high-resolution images, a method called digital image correlation.

Oxygen deprivation at birth could increase the risk of cardiovascular disease

Photo Credit: Alexander Grey

An observational study at Karolinska Institutet shows that babies suffering oxygen-deficiency complications at birth are almost twice as likely to develop cardiovascular disease during childhood and early adulthood as those without such complications. Still, the absolute risk of cardiovascular disease is very low at a young age. The findings are published in the journal The Lancet Regional Health – Europe.

According to the researchers, the study could be the first of its kind to examine how complications related to asphyxiation at birth – something that occurs in about four million babies a year globally – affects the risk of cardiovascular disease later in life. Previous research has mostly concentrated on the association between asphyxia in the neonatal period and brain development.

Despite the relatively high risk, the absolute number of babies who suffer from cardiovascular disease despite asphyxiation at birth is very low. After the 30-year follow-up period, only 0.3 percent of those with asphyxia-related complications had a cardiovascular diagnosis, compared with 0.15 percent of those without complications.

Since the study was observational, the researchers are unable to establish any causality or propose any underlying mechanisms.

New 3D model shows how cadmium exposure may affect heart development

2D model showing how the pluripotent stem cells react to human relevant doses of cadmium over 8 days. From the control in the first panel, to the last panel, researchers can see how the differentiation to cardiomyocytes is inhibited with different doses of cadmium.
Credit: National Institutes of Health

NIH researchers develop new tools to demonstrate how environmental agents can lead to diseases.

Researchers have developed a three-dimensional model that shows how exposure to cadmium might lead to congenital heart disease. Affecting nearly 40,000 newborns a year, congenital heart disease is the most common type of birth defect in the United States. The model was created by scientists at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health.

Cadmium is a metal that can be released into the environment through mining and various industrial processes, and it has been found in air, soil, water, and tobacco. The metal can enter the food chain when plants absorb it from soil. Previous studies suggested that maternal exposure to cadmium might be a significant risk factor for congenital heart disease.

Using models derived from human cells and tissues, called in vitro models, researchers designed a 3D organoid model that mimics how the human heart develops. The researchers saw how exposure to low levels of cadmium can block usual formation of cardiomyocytes, which are the major type of cells that form the heart. In doing so, they revealed the biological mechanisms that might explain how cadmium could induce heart abnormalities.

Pancreatic cancer could be diagnosed up to three years earlier

The desmoplastic reaction is a prominent pathological characteristic of pancreatic cancer. 
Credit: National Cancer Institute

Pancreatic cancer could be identified in patients up to three years earlier than current diagnoses, new research suggests. Weight loss and increasing blood glucose levels are early indicators of pancreatic cancer and could lead to a timelier diagnosis, helping to improve survival rates.

In the largest study of its kind, researchers from the University of Oxford, in partnership with Pancreatic Cancer Action and the University of Surrey, investigated signs of pancreatic cancer, including weight loss, hyperglycemia and diabetes and demonstrated the timelines for when they develop in relation to cancer. The pancreas is a vital organ with two key functions, to produce insulin and digestive enzymes. Cancer can affect one or both of these functions leading to the above symptoms. Currently, almost 90 per cent of people with pancreatic cancer are diagnosed too late for curative treatment.

Lead author Dr Agnieszka Lemanska, Lecturer in Data Science at the University of Surrey, said: 'Due to the difficulty in detecting pancreatic cancer, survival rates are extremely poor compared to other cancers, with less than 10 per cent of people surviving five years or more after diagnosis.

'Weight loss and increased blood glucose are recognized symptoms of pancreatic cancer. However, the extent of these symptoms and when they manifest have been unknown. Knowing when they develop will help clinicians to diagnose this deadly cancer, meaning treatment can begin earlier.'

Overcoming resistance to colon cancer treatment

Colorectal cancer cells after treatment with FOLFORIXI chemotherapy for 34 weeks. Cell fibers (in green) and nuclei (in blue).
Credit: UNIGE-Nowak-Sliwinka

Colorectal cancer is one of the most common cancers. Its treatment is mainly based on chemotherapy. However, over time, chemotherapy induces resistance in the majority of patients, who end up being unresponsive to the drugs. As a result, the five-year survival rate for those affected is still low. After succeeding in reproducing this resistance in the laboratory, a team from the University of Geneva (UNIGE) has found a way to overcome it. The team has used an optimized combination of drugs belonging to the class of tyrosine kinase inhibitors, which take different pathways to attack cancer cells than chemotherapy. These results, to be found in the journal Cancers, open up new avenues for overcoming treatment resistance and for developing new therapies that are more targeted than chemotherapy.

Colorectal cancer is the third most diagnosed cancer in the world and second only to lung cancer in terms of mortality. It most often develops from the age of 50 in the terminal part of the colon. It results from a change in the DNA of certain cells present in this organ. These cells become cancerous and proliferate in an uncontrolled manner until they form a primary tumor. As in many cancers, these cells can migrate to other parts of the body and form secondary tumors. This is known as metastatic cancer.

While genetics play a role in the development of the disease, the presence of inflammatory bowel diseases (e.g. Crohn’s disease) and certain dietary habits (alcohol, red meat) are also risk factors. In the case of a primary tumor, treatment is based on surgery and chemotherapy. In the case of secondary tumors, it is based on a combination of chemotherapies. These treatments are non-targeted and aggressive. They cause significant side effects. They also lead to progressive resistance to treatment in the majority of patients.

Metabolite product from pomegranate: Researchers identify way to boost tumor-fighting immune cells

A metabolite from pomegranates boosts tumor-fighting T cells, according to a study by Georg-Speyer-Haus, Goethe University Frankfurt and the LOEWE Centre Frankfurt Cancer Institute (FCI).
Photo credit: Markus Bernards

As part of an interdisciplinary project of the LOEWE Centre Frankfurt Cancer Institute (FCI), researchers from the Georg-Speyer-Haus in Frankfurt am Main, Germany, and Goethe University Frankfurt have succeeded in identifying a new approach for the therapy of colorectal cancer. In preclinical models and studies on human immune cells, they found that urolithin A, a metabolite product from pomegranate, sustainably improves the function of immune cells in their fight against cancer. After treatment with urolithin A, tumor-fighting immune cells become T memory stem cells which, due to their ability to divide, constantly supply the immune system with rejuvenated, non-exhausted T cells.

Colorectal cancer remains a disease with high mortality rates in advanced stages. In recent years, numerous research findings have improved early diagnosis and therapy, although unfortunately not all patients respond adequately to novel therapeutic approaches. Current research suggests that one characteristic of tumor diseases is immune dysfunction: immune cells that are supposed to fight the tumor are systematically suppressed by the tissue surrounding the tumor, the tumor microenvironment. As a result, T cells, which are our body's natural immune response against cancer, are restricted in their function, allowing the tumor to grow and spread uncontrollably.

Autistic people are more likely to experience depression and anxiety during pregnancy

Credit: PetraSolajova

Autistic people are more vulnerable to depression and anxiety during pregnancy, according to new research from the University of Cambridge. The results are published in the Journal of Autism and Developmental Disorders and have important implications for supporting autistic people during pregnancy.

In the study, led by researchers at the Autism Research Centre, 524 non-autistic people and 417 autistic people completed an online survey about their experience of pregnancy. Anyone who was pregnant at the time of responding or had previously given birth was eligible to take part.

The study revealed that autistic parents were around three times more likely than non-autistic parents to report having experienced prenatal depression (9% of non-autistic parents and 24% of autistic parents) and anxiety (14% of non-autistic parents and 48% of autistic parents).

Autistic respondents also experienced lower satisfaction with pregnancy healthcare. Autistic respondents were less likely to trust professionals, feel that professionals took their questions and concerns seriously, feel that professionals treated them respectfully, and be satisfied with how information was presented to them in appointments. Furthermore, autistic respondents were more likely to experience sensory issues during pregnancy and more likely to feel overwhelmed by the sensory environment of prenatal appointments.

Sand serves up a possible cure for obesity

Engineered particles of purified sand could be the next anti-obesity therapy as new research from the University of South Australia published in journal MPDI Pharmaceutics shows that porous silica can prevent fats and carbohydrates from being adsorbed in the body.

The engineered silica particles are made from purified sand and are optimally designed with a high surface area that enables them to soak up large amounts of digestive enzymes, fats, and sugars within the gastrointestinal tract.

Funded by the Channel 7 Children’s Research Foundation, the study is the first to validate how porous silica particles can impede digestive processes and stop fat and sugar adsorption.

Developed in partnership with Glantreo Limited, the new silica-based therapy will be gentler on the stomach with fewer of the unpleasant side effects associated with the mainstream anti-obesity drug, Orlistat.

Lead researcher, UniSA’s Dr Paul Joyce says this breakthrough finding could change the health outcomes for billions of people struggling with obesity.