UM scientist develops innovative strategy to combat childhood brain cancer

Dr. Tanveer Sharif
Photo Credit: Courtesy of University of Manitoba

A discovery made by a University of Manitoba researcher could lead to safer and more effective treatments for childhood brain cancer.

Dr. Tanveer Sharif, assistant professor of pathology at the Max Rady College of Medicine, Rady Faculty of Health Sciences, is studying a childhood brain cancer called Group 3 medulloblastoma and he’s developed an approach to target cancer cells using precision medicine.

“Brain tumors are the leading cause of cancer-related death in people under the age of 20 and medulloblastoma is the most common childhood brain malignancy,” said Sharif, who is a Canadian Cancer Society Emerging Scholar. “Current treatment options for this deadly cancer are very toxic and haven’t changed much over the last 20 years. For patients who do survive, they suffer from long-lasting side effects linked to chemotherapy and radiation treatments. There is an urgent need to have a safer therapeutic strategy for medulloblastoma.”

Sharif’s findings were published today in Nature Communications, and his research is supported by the Canadian Institutes of Health Research.

Stress increases Alzheimer’s risk in female mice but not males

Stress causes the levels of Alzheimer's proteins to rise in females' brains but not males' brains, according to a new study in mice by researchers at Washington University School of Medicine in St. Louis. This difference may contribute to women's greater risk of developing Alzheimer's disease.
Photo Credit: Karolina Grabowska

Women are about twice as likely as men to be diagnosed with Alzheimer’s disease. Some of that is age; in the U.S., women outlive men by five to six years, and advanced age is the strongest risk factor for Alzheimer’s. But there’s more to it than that, so Alzheimer’s researchers continue to look for other reasons why women have an elevated risk of the deadly neurodegenerative disease.

Stress may be one such reason. A study by researchers at Washington University School of Medicine in St. Louis shows that the effect stress has on the brain differs by sex, at least in mice. In stressful situations, levels of the Alzheimer’s protein amyloid beta rises sharply in the brains of females but not males. In addition, the researchers identified a molecular pathway that is active in brain cells from female mice but not male mice, and showed that it accounts for the divergent responses to stress.

The findings, published May 2 in Brain, add to a growing collection of evidence that sex matters in health and disease. From cancer to heart disease to arthritis, scientists have found differences between males and females that could potentially affect how men and women respond to efforts to prevent or treat chronic diseases.

Exercise Increases the Number of Cancer-Destroying Immune Cells in Cancer Patients

Two new Finnish studies show that short bouts of light or moderate exercise can increase the number of immune cells in the bloodstream of cancer patients.
Photo Credit: Zen Chung

Exercise decreases the risk of cancer and reduces side effects of cancer treatments. In addition, it improves patients’ quality of life and the prognosis of cancer patients.

 “It was previously thought that cancer patients should just rest after a cancer diagnosis. Today, we have more and more researched information that exercise can even improve the prognosis of cancer. However, it is not yet fully known how exercise controls cancer,” explains Research Assistant Tiia Koivula.

Previous preclinical studies have found that exercise affects the functioning of the immune system so that more immune cells are transferred to the tumor site and they become more active in destroying cancer cells. Two studies conducted at the Turku PET Centre of the University of Turku in Finland aimed to find out whether a short exercise bout affects the mobilization of immune cells in cancer patients.

“Eat, Sleep, Console” reduces hospital stay and need for medication among opioid-exposed infants

Photo Credit: Fujikama

Researchers have found the “Eat, Sleep, Console” (ESC) care approach to be more effective than using the Finnegan Neonatal Abstinence Scoring Tool (FNAST) to assess and manage opioid-exposed newborns, according to a national, randomized controlled clinical trial funded by the National Institutes of Health. Newborns cared for with ESC were medically ready for discharge approximately 6.7 days earlier and 63% less likely to receive medication as part of their treatment, compared to newborns cared for with FNAST. ESC prioritizes non-pharmacologic approaches to care, such as a low-stimulation environment, swaddling, skin-to-skin contact and breastfeeding. ESC also encourages parental involvement in the care and assessment of their infants. These findings are based on the hospital outcomes of a large and geographically diverse group of opioid-exposed infants. A two-year follow-up study of a subset of infants is ongoing. The current findings are published in the New England Journal of Medicine.

“Medical care for newborns who were exposed to opioids during pregnancy varies widely across hospitals,” said Diana W. Bianchi, M.D., director of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), which co-led the study with the NIH Environmental Influences on Child Health Outcomes (ECHO) Program. “These findings are an important step toward standard, evidence-based guidance for the care of these infants.”

Urologists to perform world’s first bladder transplant

The Keck Medicine of USC surgical team evaluates the integrity of a bladder during the research and development stage of bladder transplantation.
Photo Credit: Courtesy of USC Urology

No one has ever performed a bladder transplant in humans. But that may be about to change.

Urologists with Keck Medicine of USC have launched a clinical trial to perform the world’s first human bladder transplant.

The trial is actively screening potential participants for this first-ever type of transplantation.

During the procedure, the patient’s diseased bladder will be removed and replaced with a healthy bladder from a deceased donor.

“Transplantation is a lifesaving treatment option for conditions affecting many major organs, and transplanting a bladder could be a historic step in improving lives,” said Inderbir Gill, MD, founding executive director for USC Urology, part of Keck Medicine. Gill is also the principal investigator of the clinical trial and leading the transplantation efforts. “We could be on the verge of a medical advance that has the potential to revolutionize how we treat terminally compromised bladders.”

Study unlocks potential breakthrough in Type 1 diabetes treatment

Omid Veiseh and Boram Kim. Kim is holding a medical-grade catheter similar to ones used in the study experiments.
Photo Credit: Gustavo Raskosky/Rice University

For the over 8 million people around the globe living with Type 1 diabetes, getting a host immune system to tolerate the presence of implanted insulin-secreting cells could be life-changing.

Rice University bioengineer Omid Veiseh and collaborators identified new biomaterial formulations that could help turn the page on Type 1 diabetes treatment, opening the door to a more sustainable, long-term, self-regulating way to handle the disease.

To do so, they developed a new screening technique that involves tagging each biomaterial formulation in a library of hundreds with a unique “barcode” before implanting them in live subjects.

According to the study in Nature Biomedical Engineering, using one of the alginate formulations to encapsulate human insulin-secreting islet cells provided long-term blood sugar level control in diabetic mice. Catheters coated with two other high-performing materials did not clog up.

“This work was motivated by a major unmet need,” said Veiseh, a Rice assistant professor of bioengineering and Cancer Prevention and Research Institute of Texas scholar. “In Type 1 diabetes patients, the body’s immune system attacks the insulin-producing cells of the pancreas. As those cells are killed off, the patient loses the ability to regulate their blood glucose.”

Chest E-Tattoo Boasts Major Improvements in Heart Monitoring

A new flexible, wearable medical device could provide a major boost in the fight against heart disease, the leading cause of death in the United States.
Photo Credit: University of Texas at Austin / Cockrell School of Engineering

A team led by researchers at The University of Texas at Austin has developed an ultrathin, lightweight electronic tattoo, or e-tattoo, that attaches to the chest for continuous, mobile heart monitoring outside of a clinical setting. It includes two sensors that together provide a clear picture of heart health, giving clinicians a better chance to catch red flags for heart disease early.

“Most heart conditions are not very obvious. The damage is being done in the background and we don’t even know it,” said Nanshu Lu, a professor in the Department of Aerospace and Engineering Mechanics and a lead author of the study. “If we can have continuous, mobile monitoring at home, then we can do early diagnosis and treatment, and if that can be done, 80% of heart disease can be prevented.”

The study is published in Advanced Electronic Materials.

Toward a Therapy for a Rare Genetic Disease

Researchers have designed a “mini gene” that could eventually be developed into a gene therapy for Usher Syndrome type 1F
Photo Credit: Subin

Usher Syndrome type 1F is a rare but severe genetic disease that causes deafness, lack of balance, and progressive blindness.

Now, a team led by researchers at Harvard Medical School, Massachusetts Eye and Ear, and The Ohio State University has made an important first step toward developing a gene therapy for the disease.

The research, conducted in mice, is described Apr. 26 in Nature Communications.

The scientists designed a “mini gene” — a shortened version of a gene — to replace the gene that is mutated in Usher 1F. The mutation renders hair cells inside the inner ear incapable of producing a key protein involved in sound transmission. In mice, the mini gene increased production of the missing protein, enabling the hair cells to sense sound and restoring hearing.

Because vision loss in Usher 1F involves a slightly different form of the same protein, the researchers say the same approach may be useful for preventing blindness.

“Patients with Usher 1F are born with profound hearing loss and progressive vision loss, and so far, we have been able to offer very few solutions to these families,” said co-senior author Artur Indzhykulian, HMS assistant professor of otolaryngology–head and neck surgery at Mass Eye and Ear.

This killer protein causes pancreatic cancer

Mouse pancreas cells with high levels of the protein SRSF1; CSHL Professor Adrian Krainer found that mice with high levels of SRFS1 tend to exhibit intraepithelial neoplasia—a known precursor to the most common form of pancreatic cancer.
Image Credit: Cold Spring Harbor Laboratory

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer. It’s also one of the deadliest. More than 90% of PDAC patients die within five years of diagnosis. Usually, by the time the cancer is identified, it has already spread.

“PDAC is often found too late for treatments like chemotherapy and surgery to be very effective,” Cold Spring Harbor Laboratory (CSHL) Professor Adrian Krainer says. “But if we can clearly understand the underlying genetic mechanisms of PDAC, this might lead to earlier diagnoses and new types of therapies.”

Krainer and CSHL Postdoc Ledong Wan partnered with CSHL Professor David Tuveson to explore the role of a genetic process called RNA splicing in pancreatic cancer. RNA splicing helps DNA deliver instructions to cells for protein production. The team zeroed in on a splicing-regulator protein called SRSF1. They found that high levels of SRSF1 cause inflammation, or pancreatitis. This jumpstarts PDAC tumor development.

Near-universal T cell immunity towards a broad range of bacteria

Neutralizing the bacterially derived cytotoxic bomb: the pneumococci lie in the background, an array of macrophages and dendritic cells are arranged around the central image of a T cell. Rows of TCRs interacting with the identified pneumolysin epitope bound to HLA (white) cross the length and breadth of the artwork, emphasizing their centrality in the immune response.
Illustration Credit: Dr. Erica Tandori.

Typically, T cells of the immune system respond to a specific feature (antigen) of a microbe, thereby generating protective immunity. As reported in the journal Immunity, an international team of scientists have discovered an exception to this rule. Namely, a group of divergent bacterial pathogens, including pneumococci, all share a small highly conserved protein sequence, which is both presented and recognized by human T cells in a conserved population-wide manner.

The study set out to understand immune mechanisms that protect against pneumococcus, a bacterial pathobiont that can reside harmlessly in the upper respiratory mucosae but can also cause infectious disease, especially in infants and older adults, which can range from middle ear and sinus infections to pneumococcal pneumonia and invasive bloodstream infections.

Most currently used pneumococcal polysaccharide-based conjugate vaccines (PCVs) are effective against 10–13 serotypes, but growing serotype replacement becomes a problem.

How to increase the chance of survival in older patients with head and neck cancer

Prof. Dr. Nils Nicolay,
Photo Credit: Stefan Straube

Should patients over the age of 70 with head and neck cancer receive aggressive combined radiotherapy and chemotherapy? This is a controversial issue among patients, their families and health professionals. A large-scale international study involving Leipzig University Hospital proves the effectiveness of this combined treatment in older patients. The findings have recently been published in the journal JAMA Network Open.

As a result of demographic change, the proportion of older oncology patients is rising sharply. Compared to younger patients, cancer treatment is highly individualized due to more frequent and sometimes severe comorbidities, increasing age-related infirmities and reduced physical fitness. It is also important to consider the side effects of treatment, which can affect quality of life. The standard treatment for head and neck cancer is either surgical removal of the tumor followed by radiotherapy, or organ-preserving radiotherapy in combination with chemotherapy. The use of concomitant chemotherapy is particularly controversial because of the physical strain and side effects in older patients. So far, there is only a limited amount of trial data on the best treatment.

COVID-19 vaccine appears more effective if received around midday

A new study led by Washington University School of Medicine in St. Louis suggests that circadian rhythm — the natural cycle of physical and other changes our bodies go through in a 24-hour period — may affect the body’s response to the COVID-19 vaccine. The research suggests that vaccines given around the middle of the day may prevent more infections than those given at other times.
Image Credit: Scientific Frontline

A study from Washington University School of Medicine in St. Louis indicates that the COVID-19 mRNA vaccine may be more effective at preventing infections if doses are given around the middle of the day rather than at other times. The researchers believe circadian rhythm — the natural cycle of physical and other changes our bodies go through in a 24-hour period — may affect the body’s response to the vaccine.

Further, they found that the correlation was strongest in children and teenagers, as well as adults over age 50.

The study is published April 25 in The Journal of Clinical Investigation.

New insights on the risk of atrial fibrillation in children and adolescents

Image Credit: PublicDomainPictures

Researchers at Karolinska Institutet have investigated the relationship between premature birth and fetal growth and the risk of developing atrial fibrillation up to middle age. The study, published in JAMA Pediatrics, shows a slightly increased risk, especially in people who were born prematurely or who were large at birth. Low fetal growth was associated with an increased risk of atrial fibrillation only up to the age of 18.

For a few decades, the prevalence of atrial fibrillation at a young age has increased slightly, albeit from low levels.

"Atrial fibrillation at a young age can impose a heavy socio-economic burden on the individual, and more knowledge is needed about the underlying causes of the disease. Our findings can highlight the need to monitor and prevent the disease in more groups with an increased risk of cardiovascular disease", said the study's first author Fen Yang, doctoral student at Department of Global Public Health, Karolinska Institutet.

Rare variants of an inflammation 'brake' gene may help reveal outcomes of kidney disease

Paradoxically, a gene variant that increases inflammation also has a protective effect on the kidneys. Seen here, kidney cells nuclei (blue) and an influx of immune regulatory cells (pink) that prevent damage in an injured kidney.
Photo Credit: Garvan Institute of Medical Research

A gene that controls inflammation could pave the way for more precise disease diagnostics and personalized treatments for kidney disease. 

The discovery of variants of an inflammation ‘brake’ gene brings scientists a step closer to personalized treatment for people at risk of kidney disease and kidney failure. 

Researchers at UNSW Sydney, the Garvan Institute of Medical Research, and Westmead Hospital, found that common genetic variants of TNFAIP3, which increase inflammation in the body, can paradoxically protect the kidneys from damage in the short term.  

“We wanted to investigate whether inherited differences in how people regulate inflammation could lead to better or worse kidney health outcomes,” says Professor Shane Grey, senior author of the paper and Head of the School of Biotechnology and Biological Sciences (BABS) at UNSW. 

The findings, published today in the journal Kidney International, could be used to help determine how well people will recover from kidney injury.  

“Our discovery that some genetic variants can be protective against inflammation could lead to a simple genetic test that helps predict the risk of kidney disease for patients,” says Prof. Grey.   

Increased risk of testicular cancer in people with neuropsychiatric disabilities

Left: Ingrid Glimelius, professor at the Department of Immunology, Genetics and Pathology, Uppsala University
Right: Anna Jansson, PhD student at the Department of Immunology, Genetics and Pathology, Uppsala University
Photo Credit: Ewa Ahlin

A new study from researchers at Uppsala University and the Academic Hospital shows that men who have a neuropsychiatric disability, such as autism and ADHD, also have a slightly increased risk of suffering from the testicular cancer form seminoma. This is the first study to show such a relationship and the results are published in the scientific journal British Journal of Cancer.

Testicular cancer is the most common cancer disease in young men and the underlying causes are still very unknown.

"Since you can have a testicular cancer removed and thus cure the disease, it is important to seek care on time if you feel a lump in the testicle", says Ingrid Glimelius, chief physicist at the oncology clinic, Academic Hospital, and professor at Uppsala University.

The new study has focused on patients who have had testicular cancer in Sweden. A total of 6,166 patients have been included and compared with 61,660 age-matched but without testicular cancer. Registry data have been invested where psychiatric diagnoses prior to cancer diagnosis were more common in patients affected by testicular cancer than in the control group.

Discovery identifies those likely to experience life-threatening dengue fever

(L-R) Co-first author and PhD student Stephanie Studniberg with senior researcher, Monash BDI’s Professor Diana Hansen.
Photo Credit: WEHI

Scientists have discovered cell populations in blood which clearly indicate whether a person infected with dengue fever is likely to progress to life-threatening severe disease or not.

About half of the world’s population is at risk of dengue fever, with almost 400 million annual cases. More will be at risk as global warming enables the spread of mosquito strains that carry the virus.

Until now, there has been no accurate way to predict which patients will progress to severe dengue fever. The new finding uses immune cells to grade potential severity, paving the way for improved patient management, health system savings, and the development of a biomarker test.

Published in the Journal of Biomedical Science, the international research team, led by Professor Diana Hansen at the Monash Biomedicine Discovery Institute, included WEHI in Melbourne, and Dr Tedjo Sasmono at the Eijkman Centre in Jakarta, Indonesia.

The wound dressing that can reveal infection

The wound dressing is made of tight mesh nanocellulose, preventing bacteria and other microbes from getting in. At the same time, the material lets gases and liquid through.
Photo Credit: Olof Planthaber

A nanocellulose wound dressing that can reveal early signs of infection without interfering with the healing process has been developed by researchers at Linköping University. Their study, published in Materials Today Bio, is one further step on the road to a new type of wound care.

The skin is the largest organ of the human body. A wound disrupts the normal function of the skin and can take a long time to heal, be very painful for the patient and may, in a worst-case scenario, lead to death if not treated correctly. Also, hard-to-heal wounds pose a great burden on society, representing about half of all costs in out-patient care.

In traditional wound care, dressings are changed regularly, about every two days. To check whether the wound is infected, care staff have to lift the dressing and make an assessment based on appearance and tests. This is a painful procedure that disturbs wound healing as the scab breaks repeatedly. The risk of infection also increases every time the wound is exposed.

Durable, low-cost COVID-19 vaccine could help fill in gaps around the world

A protein-based COVID-19 vaccine developed by researchers at Stanford Medicine and their colleagues may be ideal for infants.
Image Credit: Gerd Altmann

In a study led by Stanford Medicine researchers, a low-cost COVID-19 vaccine that does not require refrigeration provided immunity in rhesus monkeys for one year.

A low-cost, protein-based COVID-19 vaccine tested in rhesus monkeys by Stanford Medicine researchers and colleagues offered immunity against known variants for at least one year. Researchers hope the vaccine, which can remain unrefrigerated for up to two weeks and may be especially beneficial for infants, will help alleviate the need for boosters while improving herd immunity around the world.

If the vaccine succeeds in human trials, it could be an alternative to the mRNA vaccines widely used for COVID-19, without drawbacks such as high expense and low-temperature storage requirements. Protein-based vaccines, which use protein fragments of the target virus rather than the whole virus, have been used for decades to protect against diseases such as shingles and hepatitis.

“Our motivation was to come up with a vaccine that would provide worldwide access to vaccination,” said Peter Kim, PhD, the Virginia and D.K. Ludwig Professor in Biochemistry. “In the case of the mRNA vaccines, for example, they are expensive, difficult to make and require storage in freezers. So, we wanted to solve those problems with this vaccine.”

Graphene ‘tattoo’ treats cardiac arrhythmia with light

Graphene implant on tattoo paper
Photo Credit: Ning Liu/University of Texas at Austin

First graphene-based cardiac implant senses irregularities, then stimulates the heart

Researchers led by Northwestern University and the University of Texas at Austin (UT) have developed the first cardiac implant made from graphene, a two-dimensional super material with ultra-strong, lightweight and conductive properties.

Similar in appearance to a child’s temporary tattoo, the new graphene “tattoo” implant is thinner than a single strand of hair yet still functions like a classical pacemaker. But unlike current pacemakers and implanted defibrillators, which require hard, rigid materials that are mechanically incompatible with the body, the new device softly melds to the heart to simultaneously sense and treat irregular heartbeats. The implant is thin and flexible enough to conform to the heart’s delicate contours as well as stretchy and strong enough to withstand the dynamic motions of a beating heart.

After implanting the device into a rat model, the researchers demonstrated that the graphene tattoo could successfully sense irregular heart rhythms and then deliver electrical stimulation through a series of pulses without constraining or altering the heart’s natural motions. Even better: The technology also is optically transparent, allowing the researchers to use an external source of optical light to record and stimulate the heart through the device. 

Protein domain common to plants and animals plays role in COVID-19 infection

ORNL scientists mutated amino acids in a receptor protein, shown in green, which diminished interaction with the SARS-CoV-2 virus spike protein, shown in red. Mutating the receptor protein hampered the virus’s ability to infect host cells.
Image Credit: ORNL, U.S. Dept. of Energy

Oak Ridge National Laboratory scientists exploring bioenergy plant genetics have made a surprising discovery: a protein domain that could lead to new COVID-19 treatments.

Researchers found the same plasminogen-apple-nematode, or PAN, domain studied by ORNL in plants like poplar and willow is also present in the human NRP1 receptor protein. NRP1 is less studied than the ACE-2 receptor targeted by current COVID-19 treatments, but this research shows its promise as a future therapeutic target.

By mutating amino acids called cysteine residues in the PAN domain of NRP1, researchers disrupted the ability of the SARS-CoV-2 virus to use its spike protein to invade cells, as described in iScience. ORNL scientists have also linked PAN to the growth of cancerous tumors.