Body

In the most extensive study of its kind, researchers from the University of Copenhagen, in collaboration with the Danish Pediatric Asthma Center at Herlev and Gentofte Hospital, have found a link between microorganisms living in the dust of children's beds and the children's own bacteria. The correlation suggests that microorganisms may reduce a child's risk of developing asthma, allergies and autoimmune diseases later on in life.
Invisible to the human eye, our beds are teeming with microbial life. It is life that, especially during early childhood, can affect how microorganisms in our bodies develop, and thereby how resilient we become to various diseases.

To get a better grasp of this relationship, researchers at the University of Copenhagen's Department of Biology and the Danish Pediatric Asthma Center analyzed bed dust samples from the beds of 577 infants before comparing them with respiratory samples from 542 children. It is the largest study of its kind, the aim of which was to determine which environmental factors affected the composition of microorganisms in the bed dust and if there was a correlation between bed dust microorganisms and the bacteria in the children's airways.

"We see a correlation between the bacteria we find in bed dust and those we find in the children. While they are not the same bacteria, it is an interesting discovery that suggests that these bacteria affect each other. It may prove to have an impact on reducing asthma and allergy risks in later years," explains Professor Søren J. Sørensen of UCPH's Department of Biology.

Constant sheet changing may not be necessary

The science was already clear -- a high diversity of microorganisms in the home contributes to the development of a child's resistance to a host of diseases and allergies. Beds can be a central collector of bacteria, microscopic fungi and other microorganisms.

"We are well aware that microorganisms living within us are important for our health, with regards to asthma and allergies for example, but also for human diseases such as diabetes II and obesity. But to get better at treating these diseases, we need to understand the processes by which microorganisms emerge during our earliest stages of life. And, it seems that the bed plays a role," says Søren J. Sørensen, adding:

"Microorganisms in a bed are affected by a dwelling's surroundings, where high bacterial diversity is beneficial. The simple message is that constantly changing bedsheets may not be necessary, but we need to investigate this a bit more closely before being able to say so for sure."

The benefits of rural life, pets and older siblings

A total of 930 different types of bacteria and fungi were found in the dust collected from the beds of the roughly six-month old children. The richness of bacteria depended largely upon the type of dwelling from which the sample was taken from.

Researchers studied both rural and urban dwellings. Rural homes had significantly higher levels of bacteria compared to urban apartments.

"Previous studies inform us that city-dwellers have less diverse gut flora than people who live in more rural settings. This is typically attributed to their spending greater amounts of time outdoors and having more contact with nature. Our studies demonstrate that changes in bacterial flora in bed dust can be an important reason for this difference as well," says Søren J. Sørensen

From previous studies, the researchers also know that pets, older siblings and rural living also contribute to a lowered risk of developing autoimmune diseases.

The researchers' next step is to investigate whether the differences in bacterial flora in bed dust can be correlated directly to the development of diseases such as allergies and asthma.

Diabetes is currently treated using incretin hormones to reduce the risk of cardiovascular disease and other medical issues that the illness can trigger. Now researchers from Lund University in Sweden have noted new links between these hormones and arteriosclerosis, and believe their discovery could be significant for treatment of diabetes in the future. The study is published in Diabetes Care.

When we eat, the incretin hormones GIP and GLP-1 are secreted by the intestine. These stimulate insulin secretion in the pancreas and contribute to the reduction in blood sugar to normal levels following a meal - known as the incretin effect.

This incretin effect is inhibited in those with type-2 diabetes, leading to hampered insulin production. This is why these hormones are currently therapeutic targets for treating insulin levels in diabetes patients.

In the current study, the researchers measured hormone levels in the blood.

"We saw that high levels of GIP were linked to a significantly higher risk of early signs of arteriosclerosis, while high levels of GLP-1 were instead linked to a lower risk. This link maintained statistical significance even after it was corrected for known risk factors", says Martin Magnusson, adjunct professor at Lund University and senior consultant in cardiology at Skåne University Hospital, as well as Clinical Fellow in diabetes at the Wallenberg Centre for Molecular Medicine at Lund University.

Researchers used data from the major Malmö Diet Cancer population study involving 3 342 participants, 59 percent of whom were women and whose average age was 72. Ten percent of the participants had diabetes.

Martin Magnusson's research team are also behind a study published in Diabetologia in January 2020 that showed that high levels of GIP are linked to a greater risk of cardiovascular mortality and total mortality.

The current study is the first in which researchers take measurements from people - and across a large population - to investigate the link between the levels of GIP and GLP-1 in the blood and measurements of early arteriosclerosis.

"The findings in this new study indicate that there may be a link between raised GIP levels in the blood and a risk of arteriosclerosis. As we did not have many diabetic participants in the study, we do not yet know how GIP levels affect the arteriosclerosis process in a purely diabetic population and should therefore treat the results as a basis for generating hypotheses", says Amra Jujic, postdoc at Lund University and the first author of the study.

Martin Magnusson considers the results to be in line with what earlier randomized clinical pharmaceutical studies have also shown. In treatments using GLP-1 agonists, the risk of cardiovascular morbidity fell while studies that indirectly raise GIP and GLP-1 through medicinal treatment using DPP4 inhibitors were not able to demonstrate such positive effects.

The researchers' hypothesis is that the positive effects of GLP-1 are counteracted by the potentially negative effects of GIP, and that this can explain the lack of cardiovascular-shielding effects in DPP4 inhibitors. Magnusson emphasizes that randomizing clinical studies of DPP4 inhibitors have shown that this medication is not linked to any negative cardiovascular effects and is therefore entirely safe for patients with diabetes to take.

"Our findings should absolutely not be used as an argument for diabetes patients to alter their current treatment. However, as many diabetes patients may likely be treated using a new group of medications in the future that directly stimulate both GLP-1 and the GIP receptor, there is major clinical interest in gaining clarity on what lies behind our epidemiological findings", explains Magnusson.

"The next stage will involve further investigation of the long-term cardiovascular effects of GIP and GLP-1 infusion and whether blocking the GIP receptor could represent an alternative treatment in animal studies. We also want to continue studying the links between GIP levels and cardiovascular risk in purely diabetic human populations in Andis, a project in which all new diabetes patients in Skåne are registered", concludes Jujic.

BOSTON - The success of a COVID-19 vaccine will depend not only on its efficacy, but will hinge at least as much on how fast and widely it can be delivered, the severity of the pandemic, and the public's willingness to be immunized, according to a study published in Health Affairs. The authors, who include investigator and senior author Rochelle Walensky, MD, MPH, chief of the Division of Infectious Diseases at Massachusetts General Hospital (MGH), demonstrate that far more investment is needed in ensuring that approved COVID-19 vaccines can be produced and distributed efficiently, and that more must be done to promote the public's trust in immunization and willingness to continue practices that slow the spread of the novel coronavirus.

Billions of dollars have been spent on developing COVID-19 vaccines, and preliminary evidence suggests that several candidates appear to be extraordinarily effective. "But there are lots of ways to think about the effectiveness of a vaccine," says Walensky. She teamed up with A. David Paltiel, PhD, a professor of Public Health (Health Policy) at the Yale School of Public Health (YSPH), and several other colleagues to create a mathematical model that assessed how other factors beyond a COVID-19 vaccine's efficacy might influence how well it thwarts the disease. Those factors included:

- How fast and broadly can the vaccine be produced and administered? Some candidate vaccines pose logistical challenges, such as needing to be stored in ultra-cold freezers or requiring two doses, spaced weeks apart.

- What portion of the population is willing to be vaccinated? National surveys suggest that as few as 50% of Americans say they will receive a COVID-19 vaccine.

- The severity of the pandemic when a vaccine is rolled out. The proportion of infections a vaccine is able to avert is directly related to the public's willingness to engage in mitigation behaviors, such as wearing masks and social distancing.

The mathematical model considered how these factors would influence the impact of vaccines of varying levels of efficacy. "We found that infrastructure will contribute at least as much to the success of the vaccination program as will the vaccine itself," says Paltiel. "The population benefits of vaccination will decline rapidly in the face of manufacturing or deployment delays, significant vaccine hesitancy, or greater epidemic severity."

To help ensure a vaccination program's success, Walensky says that significantly greater investment is needed in an infrastructure to deliver COVID-19 vaccines. Moreover, powerful public messages and on-the-ground implementation strategies at the local level are also necessary to help overcome skepticism about vaccines, especially in underserved populations.

Likewise, the Health Affairs study showed that even a highly effective vaccine will struggle to control COVID-19 if infection rates continue to rise. "If I have a cup of water, I can put out a stove fire. But I can't put out a forest fire, even if that water is 100% potent," says Walensky, emphasizing the public's role in keeping the infection rate low by mask wearing and social distancing. "We'll get out of this faster if you give the vaccine less work to do."

The last decade has been marked by a series of remarkable discoveries identifying how the universe is composed. It is understood that the mysterious substance dark matter makes up 85 % of the matter in the universe. Observable matter in the universe consists of ionized particles. Thus, a profound understanding of ionized matter and its interaction with light, could lead to a deeper understanding of the relationships at play that formed the universe. While ionized matter, or plasma, is relatively easy to generate in the lab, studying it is extremely challenging as methods that can capture ionization states and density are virtually non-existant.

In a new paper published in "Light Science & Application", a team of scientists has succeeded in directly observing the formation and interaction of highly ionized krypton plasma using femtosecond coherent ultraviolet light and a novel four-dimensional model.

Eight-fold ionized krypton ions as laser medium

In their work, the researchers employ a laser-plasma amplifier, that uses eight-fold ionized krypton ions as laser medium. Then they launch a coherent extreme ultraviolet probe pulse into this plasma that picks up signatures of the plasma conditions as it propagates through the laser-generated plasma column. This extreme ultraviolet probe pulse is then analyzed by diffracting it off a well-characterized nanoscale target. This method, known as coherent diffraction imaging, allows for measurement of the properties of the probe pulse carrying information about the plasma with very high resolution. "Using an extreme ultraviolet probe pulse with a wavelength short enough so that the plasma becomes transparent to interrogate the formed plasma is key," explains Prof. Dr Michael Zuerch from the University of California in Berkeley.

Unexpected discovery

"Surprisingly, we found a non-trivial spatial modulation pattern that is unexpected in a waveguide geometry. Using an adapted ab initio theory modelling the plasma-light interaction in four dimensions across multiple scales we can find excellent agreement with our experimental data. This has allowed us to ascribe the observed signal to a strongly nonlinear behavior in laser-plasma interaction generating the highly-ionized krypton plasma," elaborates Zuerch.

The experimental approach, that can be easily adopted to other relevant scenarios, validates the advanced ab initio models used to simulate the laser-plasma interaction and more generally the formation of highly-ionized plasma. An important ramification of the findings shows that you cannot create arbitrarily ionized plasmas using optical techniques. "The developed model will allow for predicting achievable conditions accurately and gives hope that very defined plasma conditions can be created by appropriate laser beam shaping," says Prof. Dr Christian Spielmann from the University of Jena. Zuerch summarized the outlook of the work: "Beyond a more profound understanding of laser-plasma interactions, our findings have impacts, for example, on the upscaling of plasma-based X-ray light sources or plasma-based fusion experiments."

LA JOLLA, CA--Unlike so many other deadly viruses, HIV still lacks a vaccine. The virus--which continues to infect millions around the world--has proven especially tricky to prevent with conventional antibodies, in part because it evolves so rapidly in the body. Any solution would require coaxing the body into producing a special type of antibody that can act broadly to defeat multiple strains of the virus at once.

This week, scientists at Scripps Research moved closer to attaining that holy grail of HIV research with a new vaccine approach that would rely on genetically engineered immune cells from the patient's body.

In experiments involving mice, the approach successfully induced broadly neutralizing antibodies--also called bnabs--that can prevent HIV infection, says principal investigator James Voss, PhD, of Scripps Research. The study appears in Nature Communications.

Voss and his team showed in 2019 that it was possible to reprogram the antibody genes of the immune system's B cells using CRISPR so the cells would produce the same broadly neutralizing HIV antibodies that have been found in rare HIV patients.

The new study shows that such engineered B cells, after being reintroduced to the body, can multiply in response to a vaccination--and mature into memory cells and plasma cells that produce high levels of protective antibodies for long periods of time in the body. The team also demonstrated that the engineered genes can be improved to make antibodies that are even more effective against the virus, using a process that normally occurs in B cells that are responding to immunization.

"This is the first time it has been shown that modified B cells can create a durable engineered antibody response in a relevant animal model," Voss explains.

He hopes that his vaccine approach may someday prevent new HIV infections and possibly offer a functional cure to those who already have HIV/AIDS. The virus is still prevalent throughout the world, with an estimated 38 million people with the disease in 2019.

Voss notes that in humans, the starting cells to create the vaccine could be obtained easily from a simple blood draw, then engineered in the lab before being reintroduced to the patient. He and his team--including first author Deli Huang, PhD, Jenny Tran, PhD, Alex Olson, PhD, and graduate student Mary Tenuta--are now exploring ways to improve the technology so that it would be accessible to the greatest number of people. Because the approach relies on delivering genes to a patient's own immune cells, this could be a significant challenge.

"People think of cell therapies as being very expensive," Voss says. "We're doing a lot of work towards trying to make the technology affordable as a preventative HIV vaccine or functional cure that would replace daily antiviral therapy."

Implantation of an S-ICD in a Patient with a DDD Pacemaker and Congenitally Corrected Transposition of the Great Arteries

In a new publication from Cardiovascular Innovations and Applications; DOI https://doi.org/10.15212/CVIA.2019.0597, Yu Zhang, Wen-Long Dai, Can-Can Lin, Qiao-Yuan Li and Cheng-Jun Guo from Beijing Anzhen Hospital, Capital Medical University, Beijing, China consider implantation of an S-ICD in a patient with a DDD pacemaker and congenitally corrected transposition of the great arteries.

Subcutaneous implantable cardioverter-defibrillator (S-ICD) therapy has become a viable alternative to conventional transvenous ICD implantation. Patients with congenitally corrected transposition of the great arteries (ccTGA) have a high risk of sudden cardiac death due to malignant arrhythmia. The interaction between the S-ICD system and the transvenous pacemaker system is not fully understood. The authors report a case of S-ICD implantation in a patient with ccTGA and a DDD pacemaker. The patient was a 30-year-old man with a previously placed pacemaker with diagnoses of congenital heart disease, ccTGA (SLL), left atrioventricular valve insufficiency, and third-degree atrioventricular block. He presented with an out-of-hospital cardiac arrest, and an S-ICD was implanted to prevent sudden cardiac death. Defibrillation checks were performed successfully. The authors tested the compatibility of the DDD pacemaker with the S-ICD and found that there was no interference between them. In conclusion, an S-ICD system is a reasonable and safe option in patients with ccTGA.

In a new publication from Cardiovascular Innovations and Applications; DOI https://doi.org/10.15212/CVIA.2019.0589, Nathan Burke, Tawanna Charlton, Hussam Hawamdeh, and Ki Park from the University of Florida College of Medicine, Gainesville, Florida, USA consider a case study of in-stent thrombosis after antiplatelet therapy conversion while awaiting coronary bypass.

In-stent thrombosis (IST) is a rare yet dangerous complication that may occur despite optimized coronary intervention in the cardiac catheterization laboratory. The authors report a case of an 81-year-old man who presented with ST-elevation myocardial infarction. Right coronary artery (RCA) occlusion was suspected. RCA angiography and percutaneous coronary intervention were performed. Complicated left coronary artery disease was subsequently discovered. Per cardiothoracic surgeon request, the patient was transitioned from ticagrelor to clopidogrel therapy in preparation for coronary artery bypass grafting. The patient experienced IST the day before surgery while receiving clopidogrel.

The authors review this case, which highlights the complexity of antiplatelet therapy choice and the role of genetic testing in evaluation of IST risk.

In a new publication from Cardiovascular Innovations and Applications; DOI https://doi.org/10.15212/CVIA.2019.0588, Yukuan Chen, Xiaohui Wu, Danchun Hu and Wei Wang, from the Shantou University Medical College, Shantou, China and Second Affiliated Hospital of Shantou University Medical College, Shantou, China consider the importance of mitochondrial-related genes in dilated cardiomyopathy.

The authors designed this study to identify potential key protein interaction networks, genes, and correlated pathways in dilated cardiomyopathy (DCM) via bioinformatics methods.

A GSE3586 microarray dataset was selected, consisting of 15 dilated cardiomyopathic heart biopsy samples and 13 nonfailing heart biopsy samples. Initially, the GSE3586 dataset was downloaded and was analyzed with the limma package to identify differentially expressed genes (DEGs). A total of 172 DEGs consisting of 162 upregulated genes and ten downregulated genes in DCM were selected by the criterion of adjusted Pvalues less than 0.01 and the log2-fold change of 0.6 or greater.

Gene Ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to view the biological processes, cellular components, molecular function, and KEGG pathways of the DEGs. Protein-protein interactions were constructed, and the hub protein modules were identified. The key genes DLD, UQCRC2, DLAT, SUCLA2, ATP5A1, PRDX3, FH, SDHD, and NDUFV1, were then selected; these are involved in a wide range of biological activities, such as the citrate cycle, oxidation-reduction processes and cellular respiration, and energy derivation by oxidation of organic compounds in mitochondria.

The authors found that currently there are no related gene-targeting drugs after exploring the predicted interactions between key genes and drugs, and transcription factors, providing greater understanding of the pathogenesis and underlying molecular mechanisms in DCM.

In a new publication from Cardiovascular Innovations and Applications; DOI https://doi.org/10.15212/CVIA.2019.0587, Yiqian Ding, Wei Li, Yanqiu Liu, Min Ye, Liangping Cheng, Donghong Liu, Hong Lin and Fengjuan Yao from The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China consider mediastinal tuberculoma mimicking malignant cardiac tumors.

In this report the authors present a rare case of mediastinal tuberculoma mimicking a malignant cardiac tumor before operation and was finally diagnosed as cardiac tuberculoma by postoperative pathological examination. The clinical manifestations of cardiac masses are diverse and lack specificity, which makes it difficult for clinicians to detect and distinguish cardiac masses. Cardiac tumors are rare but can be associated with high morbidity and mortality.

In recent years, more and more noninvasive imaging methods have been used for cardiac lesions. Two-dimensional echocardiography is considered to be a guiding standard imaging examination for the evaluation of cardiac masses. Contrast-enhanced perfusion echocardiography (CEUS) has advantages in distinguishing masses from benign and malignant tumors.

Although the case was initially not diagnosed by echocardiography and CT because of the variability of tuberculosis, Transthoracic echocardiography (TTE) is still considered the first line imaging modality for the assessment of cardiac masses. CEUS can confirm the presence of a cardiac or mediastinal mass and provide information on perfusion, which is used to complement TTE with improved detection of benign or malignant masses. Multimodality imaging in the evaluation of cardiac masses plays a pivotal role.

Buenos Aires, Argentina 19 November 2020: Lockdown due to the COVID-19 pandemic is associated with an increase in high blood pressure among patients admitted to emergency. That's the finding of a study presented at the 46th Argentine Congress of Cardiology (SAC).

SAC 2020 is a virtual meeting during 19 to 21 November. Faculty from the European Society of Cardiology (ESC) will participate in joint scientific sessions with the Argentine Society of Cardiology as part of the ESC Global Activities programme.

"Admission to the emergency department during the mandatory social isolation period was linked with a 37% increase in the odds of having high blood pressure - even after taking into account age, gender, month, day and time of consultation, and whether or not the patient arrived by ambulance," said study author Dr. Matías Fosco of Favaloro Foundation University Hospital, Buenos Aires.

Mandatory social isolation due to COVID-19 was implemented on 20 March in Argentina as a part of a general lockdown. People were told to stay at home, except for essential workers (e.g. doctors and nurses). The general public were permitted to leave home only to buy food, medicine and cleaning supplies. Schools and universities were closed, and public events were suspended.

"After social isolation began, we observed that more patients coming to emergency had high blood pressure," said Dr. Fosco. "We conducted this study to confirm or reject this impression."

The study was conducted in the emergency department of Favaloro Foundation University Hospital. The frequency of high blood pressure1 among patients aged 21 and above during the three-month social isolation (20 March to 25 June 2020) was compared to two previous time periods: the same three months in 2019 (21 March to 27 June 2019) and the three months immediately before social isolation (13 December 2019 to 19 March 2020).

Blood pressure is a standard measurement on admission to the emergency department and almost every patient (98.2%) admitted between 21 March 2019 and 25 June 2020 was included in the study. The most common reasons for admission were chest pain, shortness of breath, dizziness, abdominal pain, fever, cough, and hypertension.

The study included 12,241 patients. The average age was 57 years and 45.6% were women. During the three-month isolation period 1,643 patients were admitted to the emergency department. This was 56.9% less than during the same three months in 2019 (3,810 patients) and 53.9% lower than during the three months immediately before social isolation (3,563 patients).

During the social isolation period, 391 (23.8%) patients admitted to emergency had high blood pressure. This proportion was significantly higher compared to the same period in 2019, when it was 17.5%, and compared to the three months before social isolation, when it was 15.4% (p

Dr. Fosco said: "There are several possible reasons for the connection between social isolation and high blood pressure. For example, increased stress because of the pandemic, with limited personal contact and the onset or exacerbation of financial or family difficulties. Changed behaviours may have played a role, with higher intake of food and alcohol, sedentary lifestyles and weight gain."

Dr. Fosco noted that the reasons for admission were similar between the periods studied, so were not responsible for the increase in high blood pressure. But he said: "Patients may have felt more psychological tension during transportation to the hospital because of travel restrictions and police controls and a fear of becoming infected with coronavirus after leaving home. In addition, patients being treated for high blood pressure may have stopped taking their medicine due to preliminary warnings about possible adverse effects on COVID-19 outcomes (which were later dismissed)."

He concluded: "Blood pressure control helps prevent heart attacks and strokes and serious illness from COVID-19, so it's essential to maintain healthy lifestyle habits, even under social isolation and lockdown conditions. Many regulations related to the pandemic have now relaxed and we are investigating if this is reflected in the blood pressure of patients admitted to emergency."

Dr. Héctor Deschle, Scientific Programme Chair of SAC 2020, said: "This study illustrates the collateral damage generated by isolation. There has been a significant decrease in heart disease consultations, which inevitably leads to avoidable complications. But I would like to emphasise the psychological damage pointed out by the authors, which we perceive daily in consultations and which is expressed as fear, hopelessness, irritability, and difficulty concentrating. This affects interpersonal relationships and physical health. This study puts the spotlight on the concomitant consequences of the outbreak and the restrictions used to struggle against it."

Professor Jose Luis Zamorano, ESC regional Ambassador for Argentina at SAC 2020, said: "This very interesting study simply highlights that we as cardiologists must keep a watchful eye on our cardiology patients beyond the pandemic. If we do not treat and carefully follow our cardiac patients during the pandemic, we will see an increase of adverse outcomes in the future."

An experimental drug for neurodegenerative diseases can also reverse resistance to "last-resort" polymyxin antibiotics among bacteria that cause sepsis, a life-threatening complication from infections. The findings in mice suggest that repurposing the compound, named PBT2, could help clinicians cope with the issue of polymyxin resistance, which poses a grave threat to patients with bacterial infections. Sepsis can occur in patients with infections caused by various species of bacteria, including the gram-negative species Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. The spread of antibiotic resistance has made sepsis even more dangerous, as many of these bacteria have become resistant to both first-line antibiotics and to polymyxin antibiotics, which are only used when all other options have failed. One potential solution involves studying and repurposing drugs intended for other diseases, to try to target bacteria that have acquired antibiotic resistance. David De Oliveira and colleagues applied this approach to PBT2, an experimental compound being tested in phase 2 trials to treat Huntington's disease and Alzheimer's disease. The scientists found that PBT2 disrupted metals such as iron and zinc in polymyxin-resistant K. pneumoniae and P. aeruginosa, which resensitized the bacteria to polymyxin treatment. Combining PBT2 with polymyxin also substantially boosted survival rates and lowered bacterial loads in mice with sepsis caused by a highly invasive, polymyxin-resistant strain of K. pneumoniae. The authors call for further work to establish the safety and clinical potential of combining PBT2 with polymyxin antibiotics in humans.

Catching deadly diseases like cancer early on is key to improving patient survival odds. However, diseases are much harder to diagnose in their preliminary stages because people often haven't developed symptoms yet and only trace amounts can be found in their bodies.

Researchers in the Cockrell School of Engineering want to make it easier to catch diseases earlier in the process, improving patient outlooks and taking some of the load off the medical system. The researchers have created an approach using a nanosensor to speed up detection of trace amounts of biomarkers for early-disease diagnosis, while retaining high levels of sensitivity..

"It's highly important to detect diseases early and accurately, and to do that you need to be able to find very low concentrations of biomarkers," said Donglei (Emma) Fan, associate professor in the Walker Department of Mechanical Engineering, who led the research published recently in the journal ACS Nano. "And people want to know their results quickly and not have to wait around for hours or days."

Fan envisions her approach could help rapid disease tests that people can do at home or work, keeping them out of doctor's offices and hospitals unnecessarily. In a hospital setting, speeding up tests enables medical personnel to turn around large batches of diagnostics in hours rather than days.

"Everyone can be their own nurse to some degree, and then if there are any problems they can talk to a doctor," Fan said.

Super small sensors are important for disease diagnostics, but they face problems. The smaller the sensor, the more responsive it is to the tiny molecules. But the tradeoff for sensitivity is a slower turnaround time. The longer it takes for the sensor to connect with and identify molecules, the higher the risk of contamination, potentially decreasing the accuracy of the test.

Fan's sensing approach aims to solve the challenging problem of slow detection with ultra-small, highly sensitive. The approach increases the speed of a test by four times compared to with common sensing techniques. Fan's technique could reduce a detection from an hour or a couple hours to a matter of minutes.

And the key to that innovation comes through motorizing the sensor. Adding motion by spinning the device moves the liquid sample around, making it much more rapid for molecules and sensors to come into contact with each other.

The team is publishing its methodologies with the hope that other researchers and manufacturers will use the information to improve their sensors. Fan said the technology could be applicable to any type of sensors and any instance of sensing molecules in a liquid solution, including things like crime scene forensics to find DNA.

This project is in line with Fan's research, discovery, and development of micro/nanomotors and machines. Two years ago, her team developed a first-ever method for light-controlled electric nanomotors.

Fan notes that the team has more work to do, and its next step comes in speeding up the motor while retaining control, which should reduce test turnaround time even more.

"What we have demonstrated is not the limit," Fan said. "If we spin the sensor faster we can get even quicker detection."

The motion of magnetic particles as they pass through a magnetic field is called magnetophoresis. Until now, not much was known about the factors influencing these particles and their movement. Now, researchers from the University of Illinois Chicago describe several fundamental processes associated with the motion of magnetic particles through fluids as they are pulled by a magnetic field.

Their findings are reported in the journal Proceedings of the National Academy of Sciences.

Understanding more about the motion of magnetic particles as they pass through a magnetic field has numerous applications, including drug delivery, biosensors, molecular imaging, and catalysis. For example, magnetic nanoparticles loaded with drugs can be delivered to discrete spots in the body after they are injected into the bloodstream or cerebrospinal fluid using magnets. This process currently is used in some forms of chemotherapy for the treatment of cancer.

"We need to know more about how magnetic particles move so we can better predict how fast they move, how many will reach their targets and when and what factors influence their behaviors as they move through various fluids," said Meenesh Singh, UIC assistant professor of chemical engineering at the College of Engineering and corresponding author on the paper.

Meenesh and colleagues found that four major factors influence the motion of magnetic particles: the difference between the magnetic properties of the particles and the solution they are moving through, the gradient of the magnetic field, the magnetic interactions between particles or how much they stick together, and the interaction of electrical charges on particles with the magnetic field.

"We can build on this new knowledge to increase the specificity by which magnetic nanoparticles reach desired target tissues in the central nervous system," said Andreas Linninger, UIC professor of bioengineering at the College of Engineering and first author on the paper.

Based on these findings, the researchers created a mathematical formula with all these factors included. Using real-world data, they populated their model and were able to accurately predict the speed and location of particles in real systems.

"By using our model, physicians and researchers will be better able to design magnetic nanoparticles to deliver drugs or other molecules and do so much more accurately," Meenesh said. "This model can also predict the motion of charged magnetic particles in various applications, including the deflection of charged particles in earth's magnetosphere."

While the world reels from the spread of SARS-CoV2, the new coronavirus behind COVID-19, a much older and previously feared scourge--poliovirus--is close to being completely eradicated. The polio vaccines, developed by Jonas Salk and Albert Sabin in the mid-1950s, heralded the elimination of polio from the U.S., saving countless children from sudden paralysis and death. In the developing world, however, outbreaks of poliovirus still occur sporadically, an ironic consequence of the polio vaccine itself.

The polio vaccine comes in two types: the Salk vaccine, made with a killed virus and the Sabin vaccine, made with a live but weakened, or attenuated, virus. The Sabin vaccine has several advantages for use in the developing world, including the fact that it does not need to be kept cold, and as an oral vaccine, it does not require needles. However, because it contains a live, albeit weakened polio virus, that virus is able to evolve into more virulent forms and cause outbreaks months to years following a vaccination campaign.

In a new paper, Adam Lauring, M.D., Ph.D., of the department of microbiology & immunology and the division of infectious disease and a collaborative team describe an enterprising study that allowed them to view the evolution of the vaccine virus into a more dangerous form in real time.

"Most outbreaks of type 2 polio virus are caused by the vaccine. Then you have a problem where our best weapon is that same vaccine, so you're kind of fighting fire with fire," says Lauring.

In an effort to understand the basic biology of poliovirus and how it replicates, Lauring's lab seized an opportunity to build on an earlier study of a new vaccination campaign in semi-rural Bangladesh. This study, which was run by Mami Taniuchi, Ph.D., of the University of Virginia and Michael Famulare, Ph.D,. of the Institute for Disease Modeling in Seattle, Washington, along with a team from the International Centre for Diarrhoeal Disease Research, Bangladesh, followed households where children were vaccinated with the live attenuated virus, collecting weekly stool samples from each household member. The virus within those samples was then genetically analyzed.

"There's a lot of work being done to try and understand how the virus goes from attenuated to virulent again," says Lauring. "What we haven't known is what it is doing in those first few weeks or months. This was an opportunity to see those early steps."

The team was able to confirm three critical mutations that were inferred by previous investigators to be necessary for the virus to become virulent again, identifying for the first time the rate of mutation for those genes from week to week. They also discovered that the attenuated polio virus evolves extremely quick within hosts; much faster than what is typically seen with other viruses over these short timescales.

"There were a lot of mutations that were being selected because they helped the virus be a better virus," says Lauring. He notes that this could be a critical insight for disease surveillance purposes. Sewage could be analyzed for signs of these types of mutations, serving as an early warning system of a potential outbreak.

The work also revealed a spot of good news: while the virus excelled at evolving within a person, those changes were not easily transmitted from person to person.

"For all the evolution that happens in a person, transmission tends to put a brake on that and really slows things down," says Lauring.

Yet every now and then, an enhanced virus makes it to a new host and gains a foothold, triggering disease. The hope, explains Lauring, is that this work will "inform in a better way to tinker with the vaccine so you get fewer downsides and still maintain its upsides--that it's actually a very effective vaccine."

At a glance:

In a study in mice, researchers identify a previously unknown mechanism that fuels cancer spread.

Analyses pinpoint a specific cooperative interaction between cancer cells that enables formation of tumor metastases.

Findings shed light on mechanisms that allow tumors to invade distant organs.

Results can inform the design of future approaches to potentially prevent tumor spread.

Any given tumor is composed of a multitude of cell types that can each look or behave differently from its neighbors. An emerging body of research suggests that these differences can influence disease progression or the way a tumor responds to drugs.

Now, a new study by Harvard Medical School scientists shows that such cell diversity can also play a critical role in a cancer's ability to invade distant sites throughout the body, a process known as metastasis.

The research, conducted in mice and published in Nature Communications, identifies a transient, cooperative interaction between ovarian cancer cells that allows otherwise nonmetastatic tumor cells to metastasize.

The team isolated subpopulations of cells from human ovarian tumors and found that none had the ability to form metastatic tumors on its own. But when certain subpopulations commingled, a cooperative biochemical interaction between the cells acted as a switch that triggered metastasis.

The findings shed light on a novel mechanism that drives tumor spread and opens new paths of study to prevent or design targeted treatments against one of cancer's deadliest features.

"Crosstalk between otherwise innocuous cells within a tumor can play a key role in determining the metastatic capacity of a cancer," said senior study author Joan Brugge, the Louise Foote Pfeiffer Professor of Cell Biology in the Blavatnik Institute at HMS.

"This mechanism needs to be considered in efforts to identify relevant therapeutic targets for the extremely difficult challenge of blocking metastasis," said Brugge, who is also co-director of the Ludwig Center at Harvard.

As scientists work to better understand the role of cell diversity within tumors, evidence has hinted that cells can cooperate to increase rates of growth and spread. The details of how this occurs, however, had thus far remained unclear.

To investigate, Brugge and colleagues, led by first author Suha Naffar-Abu Amara, HMS research fellow in cell biology, studied the characteristics of individual and mixtures of cancer cell subpopulations taken from the same tumor.

They focused on a cell line derived from human ovarian cancer, which was known to form metastatic tumors when transplanted into mice. The team isolated numerous single cells and expanded each cell into a population of identical clones. Based on differences in cell shape and growth, they selected 11 of these populations for study.

Transient teamwork

When the team injected a mixture of all 11 clonal populations into the abdomens of mice, they observed robust growth and the formation of metastatic solid tumors on different organs as expected.

However, when each population was injected individually, only one clone, called CL31, exhibited significant growth. The rest were either stagnant, decreased in number or died off entirely.

Remarkably, none of the clones, including CL31, were capable of forming solid metastatic tumors on their own.

"All the clones except one just died when injected individually, and the only way to get metastases was to mix the populations together," Brugge said. "We had no idea we would observe what we did, and this was the phenomenon that drove us for years to better understand."

To identify how mixed cancer cells led to tumor spread whereas individual subpopulations did not, the team labeled each clone with a unique DNA barcode and looked at the composition of metastatic tumors.

Initially, all 11 clones were present in roughly the same numbers following transplantation into the mouse. But after a few weeks, more than 80 percent of cells were CL31 clones. By week 10, metastatic tumors had formed that were almost entirely composed of CL31. This finding, coupled with additional experiments, provided strong evidence that interactions between clonal populations were somehow allowing CL31 cells to become metastatic.

Genetic analyses revealed that CL31 cells exclusively possessed amplified levels of the gene ERBB2, which encodes a growth factor called HER2 that has been implicated in certain types of breast cancer. Notably, when the original tumor was genetically analyzed in bulk, the researchers saw small populations of cells with amplified ERBB2, confirming that the single-cell cloning approach successfully identified rare cells from the original tumor.

Searching for factors that activate ERBB2 in CL31 cells, the researchers homed in on a signaling protein called amphiregulin, which is found in elevated amounts in advanced ovarian cancers and has been associated with poor prognosis.

The team identified a specific clonal population that expresses high levels of amphiregulin. When injected together with CL31, the mixture of these two cell subpopulations was sufficient to cause metastases. This cooperative interaction involving amphiregulin helped CL31 invade and colonize other organs. But this teamwork was only temporary, as CL31 soon outcompeted its partner. After a few weeks, only CL31 cells remained in the tumors.

Further experiments revealed that exposure to amphiregulin for only a short window of time after injection of the CL31 is sufficient to act as a switch that allows CL31 to form metastatic tumors.

"Identifying the molecular mechanism underlying the clonal cooperation was challenging," Naffar-Abu Amara said. "Many working hypotheses arose and died, but eventually pieces of the puzzle started to fall into place. Watching the building blocks ultimately align was a very exciting and satisfying phase in our research."

Long road

The identification of this previously unknown mechanism driving metastasis now opens new lines of study to better understand the process and find new approaches to control it, the authors said.

The team conducted experiments that showed blocking the ability of CL31 cells to recognize amphiregulin could interfere with the formation of solid metastatic tumors. However, myriad questions must be answered before any potential clinical applications can be considered, according to Brugge and colleagues.

The study findings were based on cell and mouse models, and additional research is required to confirm whether the mechanism is similar in humans. Unlike most other cancers, ovarian cancer cells grow and spread in the fluid of the abdominal cavity, forming solid metastatic tumors on the surfaces of sites such as the diaphragm and pancreas. Further studies are needed to reveal if similar mechanisms play a role in cancers that spread through the blood or lymphatic systems.

The results also inform efforts to better understand the behaviors and interactions of different cell types within tumors, according to the authors. These dynamics are increasingly implicated as a cause in unpredictable drug sensitivity, drug resistance and properties such as metastasis. Ovarian cancer metastasis therefore offers an intriguing model for studying the evolutionary dynamics of cooperation among cancer cells, the authors wrote.

In addition, the study highlights the importance of animal models in the study of cancer. Typically, research on metastases involves comparisons between the primary tumor and a metastatic tumor, which can omit information about time-sensitive interactions.

"Because this interaction was transient, standard approaches of comparing primary and metastatic tumors are not feasible," Brugge said. "We would be blind to this kind of mechanism without employing animal models and individual clonal populations of cells."