Controlled, localized delivery of blood thinner may improve blood clot treatment

Co-authors Atip Lawanprasert (left), doctoral student in biomedical engineering, Sopida Pimcharoen (center), undergraduate student in biomedical engineering and Scott Medina (right), Penn State associate professor of biomedical engineering, analyze results related to their study of combining the anticoagulant heparin with peptide to slow down the medication's delivery at the site of a blood clot.
Photo Credit: Jeff Xu / Pennsylvania State University

Heparin has long been used as a blood thinner, or anticoagulant, for patients with blood clotting disorders or after surgery to prevent complications. But the medication remains difficult to dose correctly, potentially leading to overdosing or underdosing.

A team of Penn State researchers combined heparin with a protein fragment, peptide, to slow down the release of the drug and convey the medication directly to the site of a clot. They published their findings in the journal Small.

“We wanted to develop a material that can gradually deliver heparin over time rather than the current iteration that gets cleared from the body in a couple of hours,” said corresponding author Scott Medina, Penn State associate professor of biomedical engineering. “We also wanted to deliver the drug through the skin instead of through an IV.”

When mixed, positively charged peptides and negatively charged heparin bind to create a nanogranular paste that can be injected under the skin, forming a cache of material that is then diffused in the circulatory system and travels to blood clots when they appear. The turbulent flow of fluid near a blood clot triggers the two materials to separate, allowing heparin to begin its anticoagulating action.

Ludwig Cancer Research study uncovers novel aspect of tumor evolution and potential targets for therapy

 Ping-Chih Ho, Ludwig Lausanne Associate Member
Photo Credit: Ludwig Cancer Research

A Ludwig Cancer Research study has discovered that the immune system’s surveillance of cancer can itself induce metabolic adaptations in the cells of early-stage tumors that simultaneously promote their growth and equip them to suppress lethal immune responses.

Led by Ludwig Lausanne Associate Member Ping-Chih Ho and published in Cell Metabolism, the study details the precise mechanism by which this “immunometabolic editing” of emergent tumors occurs in mouse models of the skin cancer melanoma and identifies a novel biochemical signaling cascade and proteins that orchestrate its effects. Aside from illuminating a previously unknown dimension of tumor evolution, the findings hold significant promise for improving the efficacy of cancer immunotherapy.

“We have uncovered dozens of metabolic enzymes that contribute to immune evasion in melanoma tumors,” said Ho. “These enzymes, as well as some of the individual components of the signaling pathway we’ve identified, represent a rich trove of potential drug targets to undermine the defenses erected by immunometabolic editing. Such drugs could make tumors vulnerable to immune clearance and could also be used in combination with checkpoint blockade and other immunotherapies to overcome the resistance most cancers have to such treatments.”

New approach successfully traces genomic variants back to genetic disorders

Doctors researching DNA and genetics.
Illustration Credit: Julia Fekecs, NHGRI

National Institutes of Health researchers have published an assessment of 13 studies that took a genotype-first approach to patient care. This approach contrasts with the typical phenotype-first approach to clinical research, which starts with clinical findings. A genotype-first approach to patient care involves selecting patients with specific genomic variants and then studying their traits and symptoms; this finding uncovered new relationships between genes and clinical conditions, broadened the traits and symptoms associated with known disorders, and offered insights into newly described disorders. The study was published in the American Journal of Human Genetics.

“We demonstrated that genotype-first research can work, especially for identifying people with rare disorders who otherwise might not have been brought to clinical attention,” says Caralynn Wilczewski, Ph.D., a genetic counselor at the National Human Genome Research Institute’s (NHGRI) Reverse Phenotyping Core and first author of the paper.

Typically, to treat genetic conditions, researchers first identify patients who are experiencing symptoms, then they look for variants in the patients’ genomes that might explain those findings. However, this can lead to bias because the researchers are studying clinical findings based on their understanding of the disorder. The phenotype-first approach limits researchers from understanding the full spectrum of symptoms of the disorders and the associated genomic variants.

Antibiotic residues in water a threat to human health

Photo Credit: Thomas Hoang

Antibiotic residues in wastewater and wastewater treatment plants in regions around China and India risk contributing to antibiotic resistance, and the drinking water may pose a threat to human health, according to an analysis from Karolinska Institutet published in The Lancet Planetary Health. The researchers also determined the relative contribution of various sources of antibiotic contamination in waterways, such as hospitals, municipals, livestock, and pharmaceutical manufacturing.

” Our results can help decision-makers to target risk reduction measures against environmental residues of priority antibiotics and in high-risk sites, to protect human health and the environment,” says Nada Hanna, researcher at the Department of Global Public Health at Karolinska Institutet, and the study’s first author. “Allocating these resources efficiently is especially vital for resource-poor countries that produce large amounts of antibiotics.”

Bacteria that become resistant to antibiotics are a global threat that can lead to untreatable bacterial infections in animals and humans.

Antibiotics can enter the environment during their production, consumption and disposal. Antibiotic residues in the environment, such as in wastewater and drinking water, can contribute to the emergence and spread of resistance.

Common Fatty Acid Contributes to Temperature and Pain Sensitivity in Psoriasis Plaques

Photo Credit: Eszter Miller

A common fatty acid found in the Western diet breaks down into compounds that contribute to increased temperature and pain – but not itch – sensitivity in psoriatic lesions. The finding could lead to better understanding of how lipids communicate with sensory neurons, and potentially to improved pain and sensitivity treatments for psoriasis patients.

Linoleic acid is a fatty acid found in vegetable oils, nuts and seeds, and is one of the predominant fatty acids found in the Western diet. Metabolites from linoleic acid – the products formed when the body breaks it down through digestion – play a role in skin barrier function.

“We noticed high levels of two types of lipids derived from linoleic acid in psoriatic lesions,” says Santosh Mishra, associate professor of neuroscience at North Carolina State University and corresponding author of the research. “That led us to wonder whether the lipids might affect how sensory neurons in these lesions communicate. We decided to investigate whether their presence could be related to the temperature or pain hypersensitivity that many psoriasis patients report.”

Good hydration linked to healthy aging

NIH findings may provide early clues about increased risks for advanced biological aging and premature death.
Photo Credit: engin akyurt

Adults who stay well-hydrated appear to be healthier, develop fewer chronic conditions, such as heart and lung disease, and live longer than those who may not get sufficient fluids, according to a National Institutes of Health study published in eBioMedicine.

Using health data gathered from 11,255 adults over a 30-year period, researchers analyzed links between serum sodium levels – which go up when fluid intake goes down – and various indicators of health. They found that adults with serum sodium levels at the higher end of a normal range were more likely to develop chronic conditions and show signs of advanced biological aging than those with serum sodium levels in the medium ranges. Adults with higher levels were also more likely to die at a younger age.

“The results suggest that proper hydration may slow down aging and prolong a disease-free life,” said Natalia Dmitrieva, Ph.D., a study author and researcher in the Laboratory of Cardiovascular Regenerative Medicine at the National Heart, Lung, and Blood Institute (NHLBI), part of NIH.

Antimalarial Drug Proves Ineffective at Saving Children’s Lives

A drug used for the initial treatment of malaria failed to improve child survival in real world circumstances.
Photo Credit: Matthis Kleeb, Swiss TPH

Rectal artesunate, a promising antimalarial drug, has no beneficial effect on the survival of young children with severe malaria when used as an emergency treatment in resource-constrained settings. These are the results of a large-scale study conducted by the Swiss Tropical and Public Health Institute and local partners in three African countries.

Rectal artesunate (RAS) proves ineffective at saving the lives of young children suffering from severe malaria, according to the results of a new study. A viewpoint about these findings was published in The Lancet Infectious Diseases.

The study, which investigated a large-scale roll-out of RAS in the Democratic Republic of the Congo, Nigeria and Uganda, found that when used as an emergency treatment under real-world conditions, RAS did not improve the odds of survival for young children with severe malaria.

Technique for tracking resistant cancer cells could lead to new treatments for relapsing breast cancer patients

Breast cancer cells
Image Credit: Anne Weston - Francis Crick Institute (CC BY-NC 4.0)

Tumors are complex entities made up of many types of cells, including cancer cells and normal cells. But even within a single tumor there are a diverse range of cancer cells – and this is one reason why standard therapies fail.

When a tumor is treated with anti-cancer drugs, cancer cells that are susceptible to the drug die, the tumor shrinks and the therapy appears to be successful. But in reality, a small number of cancer cells in the tumor may be able to survive the treatment and regrow, often more persistently, causing a relapse.

In a study published in eLife, scientists from Professor Greg Hannon’s IMAXT lab at the Cancer Research UK Cambridge Institute at the University of Cambridge have developed a new technique for identifying the different types of cells in a tumor. Their method – developed in mouse tumors – allows them to track the cells during treatment, seeing which types of cells die and which survive.

The IMAXT team was previously awarded £20 million by Cancer Grand Challenges, funded by Cancer Research UK.

Why Don’t T Cells Destroy Solid Tumors during Immunotherapy?

3-D image of a T cell experiencing cell stress: endoplasmic reticulum (green), mitochondria (purple).
 Illustration Credit: Elizabeth Hunt, Thaxton lab

Led by Jessica Thaxton, PhD, MsCR, UNC School of Medicine scientists and colleagues found that targeting key proteins that control the T cell response to stress could help researchers develop more potent cancer immunotherapies.

The great hope of cancer immunotherapy is to bolster our own immune cells in specific ways to keep cancer cells from evading our immune system. Although much progress has been made, immunotherapy does not always work well. Jessica Thaxton, PhD, MsCR, in the immunotherapy group at the UNC Lineberger Comprehensive Cancer Center, wants to know why. She thinks one reason is the stress response experienced by T cells once they infiltrate solid cancers.

The Thaxton lab’s latest work, published in the journal Cancer Research, shows in detail how the stress response in T cells can lead to their inability to curtail tumor growth. Thaxton’s group found that T cells exposed to the environment of solid cancers undergo a natural response to stress that shuts off their function, limiting T cell ability to kill tumors. By manipulating multiple proteins in the stress response pathway inside T cells, Thaxton’s team showed that it was possible to overcome the intrinsic T cell stress response to allow the immune system to thwart cancer growth.

Critical illness myopathy common condition in intensive care patients

Lars Larsson performing experiments on the ICU models.
Photo Credit: Ya Wen

Critical illness myopathy (CIM) is a common complication affecting ventilator-treated intensive care patients, which can lead to increased mortality/morbidity, prolonged hospital care, impaired patient quality of life, and increased healthcare costs. reported molecular pathogenesis of CIM during prolonged ICU stay, and potential diagnostic biomarkers and therapeutic targets. The study was recently published in Journal of Cachexia, Sarcopenia and Muscle.

Over the past 65 years, intensive care units (ICUs) have undergone a significant development that has resulted in improved survival rates. But life-saving efforts are also accompanied by negative consequences for ICU patients, affecting skeletal muscle systems, including the critical illness myopathy (CIM) with muscle wasting and paralysis/paresis. The incidence of CIM is about 30% among ICU patients, and almost 100% in neuro-ICU patients exposed to prolonged controlled mechanical ventilation. Moreover, the negative consequences have become increasingly apparent during the COVID-19 pandemic.

Researchers have identified the origins of a serious illness in children

Egle Kvedaraite, doctor and researcher.
Photo Credit: Sebastien Teissier.

The origins of the serious cancer-like disease LCH have been identified by researchers from Karolinska Institutet in collaboration with Karolinska University Hospital. The findings presented in Science Immunology may lead to new, targeted treatments.

Langerhans’ Cell Histiocytosis (LCH) is a serious type of cancer-like disease that mainly affects children and can be fatal in severe cases. About five to ten children get the disease in Sweden every year, usually before the age of ten.  

The immune cells are affected by cancer mutations

LCH is a disease in which the cancer mutation occurs in the immune cells, which otherwise have the task of detecting and eliminating cancer cells. 

New Research on Antibiotic Resistant Bacteria May Be A Step Toward New Treatments for Infections

 From left to right: NSU Students Gabriela Diaz Tang, Estefania Marin Meneses
Credit: Nova Southeastern University

Antibiotic resistant bacteria pose one of the greatest threats to global public health. In 2019, deaths due to antibiotic resistant bacteria outpaced deaths due to HIV and malaria. Given the lack of innovation in the discovery of new antibiotics, it is critical to determine the mechanisms by which bacteria tolerate existing antibiotics so that we can improve their effectiveness.

One way that bacteria can tolerate antibiotics is through the inoculum effect. Essentially, the higher the density of bacteria in an infection, the more antibiotics are required to treat the infection. While the inoculum effect has been observed for nearly all known antibiotics, and has been documented since the 1960s, a common mechanism to explain inoculum effect for multiple antibiotics has not been found.

Scientists recently discovered that interactions between how fast bacteria grow and the amount of energy (or metabolism) bacteria have can explain the inoculum effect for multiple antibiotics and bacteria species. This new research also shows that providing different nutrients to the bacteria that change growth rate and energy levels can eliminate the inoculum effect.

Frequent genetic cause of late-onset ataxia uncovered by a Quebec-led international collaboration

Photo Credit: whitfieldink

Discovery will improve diagnosis and open treatment possibilities for thousands of people with this debilitating neurodegenerative condition worldwide

A new study published in the New England Journal of Medicine reports the identification of a previously unknown genetic cause of a late-onset cerebellar ataxia, a discovery that will improve diagnosis and open new treatment avenues for this progressive condition.

Late-onset cerebellar ataxias (LOCA) are a heterogeneous group of neurodegenerative diseases that manifest in adulthood with unsteadiness. One to three in 100,000 people worldwide will develop a late-onset ataxia. Until recently, most patients with late-onset ataxia had remained without a genetic diagnosis.

An international team led by Dr. Bernard Brais, a neurologist and researcher at The Neuro (Montreal Neurological Institute-Hospital) of McGill University and Dr. Stephan Züchner of the University of Miami’s Miller School of Medicine, in collaboration with neurologists from the Universities of Montreal and Sherbrooke, studied a group of 66 Quebec patients from different families who had late-onset ataxia for which an underlying genetic cause had not yet been found. Using the most advanced genetic technologies, the team found that 40 (61 per cent) of the patients carried the same novel disease-causing variant in the gene FGF14, making it the most common genetic cause of late-onset ataxia in Quebec. They found that a small stretch of repetitive DNA underwent a large size increase in patients, a phenomenon known as repeat expansion.

Biodegradable medical gowns may add to greenhouse gas

Photo Credit: National Cancer Institute

The use of disposable plasticized medical gowns – both conventional and biodegradable – has surged since the onset of the COVID-19 pandemic. Landfills now brim with them.

Because the biodegradable version decomposes faster than conventional gowns, popular wisdom held that it offers a greener option by less space use and chronic emissions in landfills.

That wisdom may be wrong.

Biodegradable medical gowns actually introduce harsh greenhouse gas discharge problems, according to new research published Dec. 20 in the Journal of Cleaner Production.

“There’s no magic bullet to this problem,” said Fengqi You, the Roxanne E. and Michael J. Zak Professor in Energy Systems Engineering, in the Smith School of Chemical and Biomolecular Engineering.

“Plasticized conventional medical gowns take many years to break down and the biodegradable gowns degrade much faster, but they produce gas emissions faster like added methane and carbon dioxide than regular ones in a landfill,” said You, who is a senior faculty fellow in the Cornell Atkinson Center for Sustainability. “Maybe the conventional gowns is not so bad.”

With Discovery, Oxygen's Role in Growth of Tumors Reconsidered

Structure of the HIF1A protein. Based on PyMOL rendering of PDB 1h2k Illustration
Credit: Emw
CC BY-SA 3.0

Yale researchers have made a discovery that changes conventional thinking about the role that oxygen plays in the growth of tumors—an area of cancer research that has been intensely studied in recent years.

The results, from the lab of Andre Levchenko, the John C. Malone Professor of Biomedical Engineering, are published in Cell Systems. Other groups collaborating on this study were directed by Chi V. Dang (Johns Hopkins University) and Kshitiz (University of Connecticut).

When tumors start running out of oxygen, they can switch on hypoxia-inducible factor (HIF-1alpha)—a transcription factor, which is a protein that controls the activity of genes. As a result of HIF-1alpha activation, the expression of hundreds of genes can change and dramatically alter the behavior of cancer cells. Although the increase in HIF-1alpha is thought to be steady, the new study led by Levchenko discovered that the levels of this molecule can also repeatedly rise and fall in small groups of cells, particularly in areas of high cell density. The effects of this oscillation are profound, as it allows cancer cells starving for oxygen to resume division and growth. It can also promote pro-cancer genes and inhibit anti-cancer genes.

AI model predicts if a covid-19 test might be positive or not

Xingquan “Hill” Zhu, Ph.D., (left) senior author and a professor; and co-author Magdalyn E. Elkin, a Ph.D. student, both in FAU’s Department of Electrical Engineering and Computer Science.
Photo Credit: Florida Atlantic University

COVID-19 and its latest Omicron strains continue to cause infections across the country as well as globally. Serology (blood) and molecular tests are the two most commonly used methods for rapid COVID-19 testing. Because COVID-19 tests use different mechanisms, they vary significantly. Molecular tests measure the presence of viral SARS-CoV-2 RNA while serology tests detect the presence of antibodies triggered by the SARS-CoV-2 virus.

Currently, there is no existing study on the correlation between serology and molecular tests and which COVID-19 symptoms play a key role in producing a positive test result. A study from Florida Atlantic University ’s College of Engineering and Computer Science using machine learning provides important new evidence in understanding how molecular tests versus serology tests are correlated, and what features are the most useful in distinguishing between COVID-19 positive versus test outcomes.

Researchers from the College of Engineering and Computer Science trained five classification algorithms to predict COVID-19 test results. They created an accurate predictive model using easy-to-obtain symptom features, along with demographic features such as number of days post-symptom onset, fever, temperature, age and gender.

Studies find Omicron related hospitalizations lower in severity than Delta and Pfizer-BioNTech COVID vaccine remains effective in preventing hospitalizations

Photo Credit: Fernando Zhiminaicela

Adult hospitalizations from Omicron-related SARS-CoV-2 (COVID-19) were less severe than Delta and the Pfizer-BioNTech vaccine (also known as Comirnaty and BNT162b2*) remains effective in preventing not only hospitalization, but severe patient outcomes associated with COVID-19, two new research studies have found.

The University of Bristol-led research, funded and conducted in collaboration with Pfizer Inc., as part of AvonCAP, is published in The Lancet Regional Health – Europe.

AvonCAP records adults who are admitted to Bristol’s two hospital Trusts – North Bristol NHS Trust (NBT) and University Hospitals Bristol and Weston NHS Foundation Trust (UHBW) with possible respiratory infection.

In the first paper ‘Severity of Omicron (B.1.1.529) and Delta (B.1.617.2) SARS-CoV-2 infection among hospitalized adults: a prospective cohort study in Bristol, United Kingdom’ researchers assessed whether Delta SARS-CoV-2 infection resulted in worse patient outcomes than Omicron SARS-CoV-2 infection, in hospitalized patients

The study aimed to provide more detailed data on patient outcomes, such as the need for respiratory support.

Antibody discovery paves way for new therapies against group A streptococcal infections

Pontus Nordenfelt Associate Professor, Infection Medicine Lund University
Source: Lund University

Researchers at Lund University in Sweden have discovered an antibody with the potential to protect against Strep A infection, as well as a rare form of antibody binding, that leads to an effective immune response against bacteria. The discovery could explain why so many Group A strep vaccines have failed.

The results are published in EMBO Molecular medicine.

Group A streptococci have several ways in which they evade the body's immune system and, when they infect us, can cause both common throat infections (strep throat), scarlet fever, sepsis, swine pox and skin infections. So far, antibiotics work against these bacteria, but should they become resistant, they will pose a major public health threat.

One strategy that the scientific community uses to find new ways of fighting bacterial infections is to create target-seeking antibodies. First, the antibodies that the body's immune system produces in the event of an infection are mapped, and then their effect on the immune system is studied. In this way, antibodies can be identified that can be used both for preventive treatment and for treatment during an ongoing infection. However, it's a challenging process, and many attempts to develop antibody-based treatments against Strep A have failed.

Molecules found in mucus could prevent cholera infection

Scanning electron microscope image of Vibrio cholerae bacteria, which infects the digestive system.
Image Credit: Zeiss DSM 962 SEM T.J. Kirn, M.J. Lafferty, C.M.P Sandoe and R.K. Taylor,

MIT researchers have identified molecules found in mucus that can block cholera infection by interfering with the genes that cause the microbe to switch into a harmful state.

These protective molecules, known as glycans, are a major constituent of mucins, the gel-forming polymers that make up mucus. The MIT team identified a specific type of glycan that can prevent Vibrio cholerae from producing the toxin that usually leads to severe diarrhea.

If these glycans could be delivered to the site of infection, they could help strengthen the mucus barrier and prevent cholera symptoms, which affect up to 4 million people per year. Because glycans disarm bacteria without killing them, they could be an attractive alternative to antibiotics, the researchers say.

“Unlike antibiotics, where you can evolve resistance pretty quickly, these glycans don’t actually kill the bacteria. They just seem to shut off gene expression of its virulence toxins, so it’s another way that one could try to treat these infections,” says Benjamin Wang PhD ’21, one of the lead authors of the study.

Prostate cancer risk prediction algorithm could help target testing at men at greatest risk

Prostate cancer is the most common type of cancer in men
Photo Credit: Shawnee D

Cambridge scientists have created a comprehensive tool for predicting an individual’s risk of developing prostate cancer, which they say could help ensure that those men at greatest risk will receive the appropriate testing while reducing unnecessary – and potentially invasive – testing for those at very low risk.

CanRisk-Prostate, developed by researchers at the University of Cambridge and The Institute of Cancer Research, London, will be incorporated into the group’s CanRisk web tool, which has now recorded almost 1.2 million risk predictions. The free tool is already used by healthcare professionals worldwide to help predict the risk of developing breast and ovarian cancers.

Prostate cancer is the most common type of cancer in men. According to Cancer Research UK, over 52,000 men are diagnosed with the disease each year and there are more than 12,000 deaths. Over three-quarters (78%) of men diagnosed with prostate cancer survive for over ten years, but this proportion has barely changed over the past decade in the UK.

Testing for prostate cancer involves a blood test that looks for a protein known as a prostate-specific antigen (PSA) that is made only by the prostate gland; however, it is not always accurate. According to the NHS website, around three in four men with a raised PSA level will not have cancer. Further tests, such as tissue biopsies or MRI scans, are therefore required to confirm a diagnosis.