New findings on how to avert excessive weight loss from COVID-19

Professor Yihai Cao.
Photo Credit: Dr. Muyi Yang.

Losing too much weight when infected with COVID-19 has been linked to worse outcomes. Now, researchers at Karolinska Institutet have discovered that SARS-CoV-2 infection fuels blood vessel formation in fat tissues, thus revving up the body’s thermogenic metabolism. Blocking this process by using an existing drug curbed weight loss in mice and hamsters that were infected with the virus, according to the study published in the journal Nature Metabolism.

“Our study proposes a completely new concept for treating COVID-19 associated weight loss by targeting the blood vessels in the fat tissues,” says Yihai Cao, professor at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, and the study’s corresponding author.

The researchers examined how different types of fat, including brown fat and visceral and subcutaneous white fat, reacted when exposed to SARS-CoV-2 and how it impacted weight in mice and hamsters. They found that the animals lost significant amounts of weight in four days and that this weight loss was preceded by the activation of brown fat and the browning of both types of white fat. These fat tissues also contained more microvessels and high levels of a signaling protein called vascular endothelial growth factor (VEGF), which promotes the growth of new blood vessels.

Corona vaccination also protects people infected with HIV

They represent the study team: Clara Bessen, Carlos Plaza Sirvent, Adriane Skaletz-Rorowski, Anja Potthoff and Agit Simsek (from left).
Photo Credit: RUB, Marquard

A study shows that booster vaccination is particularly useful.

HIV-infected people who receive antiretroviral therapy form antibodies against Sars-Cov-2 after the Corona vaccination with mRNA vaccines. However, your immune response to vaccination is less strong than that of healthy people. The difference is reduced by a third vaccination. These results were achieved by a study with a total of 91 participants, which was carried out by a research team led by Prof. Dr. Ingo Schmitz, head of the Molecular Immunology Department at the Ruhr University in Bochum. The researchers report in the journal Frontiers in Immunology.

Vaccination protection for acquired immunodeficiency

Studies have shown that Sars-Cov-2 vaccines protect otherwise healthy people well against a severe course of Covid-19. It has so far been unclear whether this will also be the case for people with acquired immune deficiency. The research team led by Ingo Schmitz and Dr. Anja Potthoff from the Walk in Ruhr (WIR) Center for Sexual Health and Medicine at the RUB University Hospital included 71 people in her study who are HIV positive and receive antiretroviral therapy. 20 HIV-negative control persons also participated. After the first, second and third vaccinations with the mRNA vaccine from Biontech / Pfizer, they examined the immune response of the participants.

The Superpowers of the Female Locust

Elongation of the body of the female locust while laying eggs in the ground
Illustration Credit: Tel Aviv University

Every mother will do anything to know that her offspring are in a safe place. The female locust, however, takes it to a whole new level: A new Tel Aviv University study has discovered that these females have superpowers. The female locust’s central nervous system has elastic properties, allowing her to stretch up to two or three times her original length when laying her eggs in the ground, without causing any irreparable damage.

“We are not aware of a similar ability in almost any living creature,” say the researchers. “Nerves in the human nervous system, for example, can stretch only up to 30% without tearing or being permanently damaged. In the future, these findings may contribute to new developments in the field of regenerative medicine, as a basis for nerve restoration and the development of synthetic tissues.”

“The superpower of the locust is almost something out of science fiction. There are only two other known examples in nature of a similar phenomenon: the tongue of the sperm whale, and a certain type of sea snail whose nervous systems are able to extend significantly due to an accordion-like mechanism they have." Prof. Amir Ayali

Wearable sensor could guide precision drug dosing

 The sensor uses microneedles that are made by cutting down clinical-grade acupuncture needles.
Image Credit: Emaminejad Lab/UCLA

For some of the powerful drugs used to fight infection and cancer, there’s only a small difference between a healing dose and a dose that’s large enough to cause dangerous side effects. But predicting that margin is a persistent challenge because different people react differently to medications — even to the same dose.

Currently, doctors can calibrate the amount of medication they administer in part by drawing blood to test the amount of medicine in a patient’s body. But results from those tests often take a day to process and only measure dosage at one or two moments in time, so they don’t help much when determining how to adjust dosage amounts in real time.

Now, a UCLA-led research team has developed a wearable patch that uses inexpensive microneedles to analyze the fluid between cells less than a millimeter underneath the skin and continuously record concentrations of medicine in the body. The technology could be a step toward improving doctors’ ability to administer precise medication doses.

In a study published in Science Advances, the investigators tested the system in rats that had been treated with antibiotics. Using data taken by the device within about 15 minutes after the medication was administered, the researchers reliably forecast how much of that drug would be effectively delivered to the animal’s system in total.

Many genes linked to alcohol and tobacco use are shared among diverse ancestries

Penn State College of Medicine researchers co-led a large genetic study that identified more than 2,300 genes predicting alcohol and tobacco use. They said that many of these genes were similar among people with diverse ancestries.
Photo Credit: Pavel Danilyuk

Penn State researchers co-led a large genetic study that identified more than 2,300 genes predicting alcohol and tobacco use after analyzing data from more than 3.4 million people. They said a majority of these genes were similar among people with European, African, American and Asian ancestries.

Alcohol and tobacco use are associated with approximately 15% and 5% of deaths worldwide, respectively, and are linked with chronic conditions like cancer and heart disease. Although the environment and culture can affect a person’s use and the likelihood of becoming addicted to these substances, genetics is also a contributing factor, according to Penn State College of Medicine researchers. They helped identify around 400 genes that are associated with certain alcohol and tobacco use behaviors in people in a prior research study.

“We’ve now identified more than 1,900 additional genes that are associated with alcohol and tobacco use behaviors,” said Dajiang Liu, professor and vice chair for research in the Department of Public Health Sciences. “A fifth of the samples used in our analysis were from non-European ancestries, which increases the relevance of these findings to a diverse population.”

Staph infection-induced kidney disease may be linked to bacterial gene mutation

Anjali Satoskar
Photo Credit: Ohio State University

Researchers aiming to predict which staph-infection patients might develop a related kidney disease have found a high frequency of gene mutations in the infecting bacteria of affected patients, which suggests these variants may play a role in the body’s initiation of the renal damage.

The kidney disorder is a fairly uncommon autoimmune complication to Staphylococcus aureus infection. Although it is potentially reversible with quick administration of appropriate antibiotics and effective treatment of the infection, it can also lead to kidney disease or kidney failure.

“There are many varieties of autoimmune nephritis. For most of them, suppressing the immune system is the first line of treatment, but this type is unique because you have both an ongoing severe infection as well as this autoimmune tissue-injury response happening at the same time. Immunosuppression is not an option while the infection is still active,” said study senior author Anjali Satoskar, clinical professor of pathology in the Ohio State University College of Medicine. “It can be a diagnostic as well as a therapeutic challenge.”

In an exploratory study, Satoskar and colleagues found a higher frequency of mutations affecting a group of Staphylococcus aureus genes in blood culture isolates from patients with staph-associated nephritis compared to patients having staph infections without development of autoimmune kidney disease.

Seaweed molecules used to improve outcomes for bypass surgery

Researchers use material made from seaweed to modify synthetic blood vessels
Photo Credit: Oleksandr Sushko

Researchers are using a natural material derived from seaweed to promote vascular cell growth, prevent blood clots and improve the performance of synthetic vascular grafts used in heart bypass surgery.

The new approach, developed and tested at the University of Waterloo, is especially important in cases involving small artificial blood vessels - those less than six millimeters in diameter - which are prone to clots that can develop into full blockages.

“There is a crucial need to develop synthetic vascular graft materials that will increase the rate of long-term functions,” said Dr. Evelyn Yim, a chemical engineering professor and University Research Chair who leads the project.

Researchers added a material called fucoidan, which is made from seaweed, to modify synthetic blood vessels. Fucoidan has a structure similar to heparin, a drug used as an anticoagulant.

Checking blood pressure in a heartbeat, using artificial intelligence and a camera

The new technology demonstrates how a camera and artificial intelligence can be used to extract cardiac signals from a person's forehead.
Photo Credit:  University of South Australia

Monitoring blood pressure using a digital camera could soon be the norm, thanks to an innovative technique demonstrated by Australian and Iraqi researchers.

Using the same remote-health technology they pioneered to monitor vital health signs from a distance, engineers from the University of South Australia and Baghdad’s Middle Technical University have designed a non-contact system to accurately measure systolic and diastolic pressure.

The researchers claim that it could replace the existing uncomfortable and cumbersome method of strapping an inflatable cuff to a patient’s arm or wrist, the researchers claim.

In a new paper published in Inventions, the researchers describe the technique, which involves filming a person from a short distance for 10 seconds and extracting cardiac signals from two regions in the forehead, using artificial intelligence algorithms.

The systolic and diastolic readings were around 90 per cent accurate, compared to the existing instrument (a digital sphygmomanometer) used to measure blood pressure, that is itself subject to errors.

Researchers developed a new cancer testing method that makes regular monitoring affordable

Asst Prof Cheow Lih Feng (right), his former PhD student Dr Elsie Cheruba (left) and their team have developed the Heatrich-BS assay, an affordable and highly sensitive blood test for cancer. This new testing method has strong potential to be used in regular cancer monitoring.
Photo Credit: National University of Singapore

The S$50 blood test has high sensitivity, comparable to the gold standard CT scan

Scientists from the National University of (NUS) have discovered a novel low-cost method of testing for cancers. Called the Heatrich-BS assay, this new test sequences clinical samples that have been heated in order to isolate cancer-specific signatures found in a patient’s blood.

The new method provides a promising non-invasive alternative to tissue biopsies. It costs around S$50 from start to finish, compared to other sequencing methods that can cost up to S$1,000 to conduct. Led by Assistant Professor Cheow Lih Feng, the team comprising researchers from the NUS Department of Biomedical Engineering under the College of Design and Engineering as well as the NUS Institute for Health Innovation & Technology, is now exploring industry partnerships to bring their technology to market.

“When you have a S$50 test, it opens up a lot of avenues because it is affordable, so you can do the test quite regularly,” said Asst Prof Cheow, pointing to the potential for their assay to be used in regular cancer monitoring.

Positively charged nanomaterials treat obesity anywhere you want

Illustration of depot-specific targeting of fat by cationic nanomaterials
Illustration Credit: Nicoletta Barolini/Columbia University

Researchers have long been working on how to treat obesity, a serious condition that can lead to hypertension, diabetes, chronic inflammation, and cardiovascular diseases. Studies have also revealed a strong correlation of obesity and cancer--recent data show that smoking, drinking alcohol, and obesity are the biggest contributors to cancer worldwide.

The development of fat cells, which are produced from a tiny fibroblast-like progenitor, not only activates the fat cells’ specific genes but also grows them by storing more lipids (adipocytes and adipose tissue). In fact, lipid storage is the defining function of a fat cell. But the storage of too much lipid can make fat cells unhealthy and lead to obesity.

Challenges in targeting fat cells

The ability to target fat cells and safely uncouple unhealthy fat formation from healthy fat metabolism would be the answer to many peoples’ prayers. A major challenge in obesity treatment is that fat tissue, which is not continuous in the body but is found piece by piece in “depots,” has been difficult to target in a depot-specific manner, pinpointed at the exact location.

There are two main kinds of fat: visceral fat, internal tissues that surround the stomach, liver, and intestines, and subcutaneous fat, found under the skin anywhere in the body. Visceral fat produces potbellies; subcutaneous fat can create chin jowls, arm fat, etc. To date, there has been no way to specifically treat visceral adipose tissue. And current treatments for subcutaneous fat like liposuction are invasive and destructive.

Researchers Develop Strategy to Thermally Stabilize Microneedle Vaccine Technology

Visual of the researcher's microneedle vaccine technology concept.
Illustration Credit: Thahn Nguyen

Researchers use sugar molecules to help eliminate the need for cold-chain storage, a common logistical hurdle for vaccine distribution

Researchers in the Department of Biomedical Engineering —a shared department between the UConn Schools of Dental Medicine, Medicine, and Engineering—unlocked a new strategy using sugar molecules to thermally stabilize their existing microneedle vaccine technology, eliminating the need for cold-chain storage.

Associate Professor Thanh Duc Nguyen from the Departments of Mechanical Engineering and Biomedical Engineering in the School of Engineering, reported this new development in a recent issue of Advanced Materials Technology. The work was led by Dr. Khanh Tran, Nguyen’s former UConn Ph.D. student currently at the Massachusetts Institute of Technology, and Dr. Tyler Gavitt, former UConn Ph.D. student currently at Duke University. Gavitt was a student of Associate Professor Steven Szczepanek in the Department of Pathobiology and Veterinary Science in the College of Agriculture, Health, and Natural Resources at UConn.

Typically, vaccinations against infectious diseases like COVID-19 require multiple painful, expensive and inconvenient injections, including a prime and several booster shots. The UConn researcher’s technology creates a self-administered microneedle patch which could be self-administered and only requires a single-time administration into skin—similar to a nicotine patch—to perform a release profile of vaccines, simulating the effect of multiple injections.

Development of the immune system before and after birth

What influence does a premature birth have on the development of the immune system? And how can the immune system be supported to ensure an optimal start in life? The researchers in the SFB/TRR PILOT are dealing with these and many other questions.
Photo Credit: University Medical Centre Freiburg

The newborn's immune system is suddenly confronted with microorganisms, food and numerous environmental influences at birth. How do the baby's immune cells prepare for this moment during pregnancy and birth? How do external influences shape the immune system immediately after birth? And what influence does an event like a premature birth have? These and many other questions about the development of the child's immune system around birth are being investigated by scientists from the Facult of Medicine at the University of Freiburg together with researchers from the LMU Munich, the University Hospital RWTH Aachen and other institutions in the Collaborative Research Center/Transregio “Perinatal Development of Immune Cell Topology (PILOT).” PILOT was approved by the German Research Foundation (DFG) on November 25, 2022, and will be funded with a total of 12 million euros for an initial period of four years starting January 1, 2023.

Commercial Dishwashers Destroy Protective Layer in Gut

Rinse aids in commercial dishwashers often contain alcohol ethoxylate. This substance damages the intestinal epithelium, which can lead to chronic diseases.

Residue from rinse agents is left behind on dishes after they are cleaned in professional-grade dishwashers. This damages the natural protective layer in the gut and can contribute to the onset of chronic diseases, as demonstrated by researchers working with organoids at the Swiss Institute of Allergy and Asthma Research.

Whether it’s at a restaurant, at school or in the barracks, commercial dishwashers help plates, glasses and cutlery become squeaky clean and dry in a matter of minutes. These practical appliances come with risks, however, as was recently discovered in a new study by researchers at the Swiss Institute of Allergy and Asthma Research (SIAF), an associated institute of the University of Zurich (UZH). One ingredient in particular found in commercial rinse agents has a toxic effect on the gastrointestinal tract.

Chemical residue on clean plates

A typical cycle in a commercial dishwasher involves circulating hot water and detergent for around 60 seconds at high pressure. Afterwards, there is a second 60-second washing and drying cycle in which water and a rinse agent are applied. “What’s especially alarming is that in many appliances, there’s no additional wash cycle to remove the remaining rinse aid,” says Cezmi Akdis, UZH professor of experimental allergology and immunology and director of the SIAF, who led the study. “This means that potentially toxic substances remain on the dishes, where they then dry in place.” When the dishes are used the next time, this dried chemical residue can easily end up in the gastrointestinal tract.

Better Than a Hole in the Head

Just as blood pressure informs heart health, intracranial pressure (ICP) helps indicate brain health. ICP sensing is the burgeoning focus of Jana Kainerstorfer's biomedical optics lab at Carnegie Mellon University. Her team is working to modernize ICP sensing approaches, which historically have been invasive and risky. Their noninvasive alternatives will ease the risk of infection, pain and medical expenses, as well as present new monitoring capabilities for patients with an array of brain injuries and conditions, from stroke to hydrocephalus.

Investigating pressure levels in the brain is a laborious task for health professionals and hasn't progressed much since the 1960s. Current practice involves drilling a hole into a patient's skull and placing a probe inside for continuous monitoring of ICP levels. It comes with the risk of infection and damaging the brain itself, and while valuable data is to have, ICP measurement is reserved only for the most critical of situations.

"At the core of it, what we've done is build a sensor alternative that doesn't require drilling a hole into the patient's head," said Kainerstorfer, an associate professor of biomedical engineering. "We recently published two papers that explore the use of optical sensors on the forehead for noninvasive ICP monitoring, using near-infrared spectroscopy and diffuse correlation spectroscopy. Both approaches represent huge strides in improving the patient experience and providing better tools to monitor pressure levels in the brain, which can be a key variable in both diagnosis and treatment decisions."

Machine learning model builds on imaging methods to better detect ovarian lesions

(From left) The top row shows an ultrasound image of a malignant lesion, the blood oxygen saturation, and hemoglobin concentration. The bottom row is an ultrasound image of a benign lesion, the blood oxygen saturation, and hemoglobin concentration.
Image Credit: Zhu lab

Although ovarian cancer is the deadliest type of cancer for women, only about 20% of cases are found at an early stage, as there are no real screening tests for them and few symptoms to prompt them. Additionally, ovarian lesions are difficult to diagnose accurately — so difficult, in fact that there is no sign of cancer in more than 80% of women who undergo surgery to have lesions removed and tested.

Quing Zhu, the Edwin H. Murty Professor of Biomedical Engineering at Washington University in St. Louis’ McKelvey School of Engineering, and members of her lab have applied a variety of imaging methods to diagnose ovarian cancer more accurately. Now, they have developed a new machine learning fusion model that takes advantage of existing ultrasound features of ovarian lesions to train the model to recognize whether a lesion is benign or cancerous from reconstructed images taken with photoacoustic tomography. Machine learning traditionally has been focused on single modality data. Recent findings have shown that multi-modality machine learning is more robust in its performance over unimodality methods. In a pilot study of 35 patients with more than 600 regions of interest, the model’s accuracy was 90%.

Blood thinning drug to treat recovery from severe COVID-19 is not effective

The HEAL-COVID trial (Helping to Alleviate the Longer-term consequences of COVID-19) is funded by the National Institute for Health and Care Research (NIHR) and the Cambridge NIHR Biomedical Research Centre. To date, more than a thousand NHS patients hospitalized with COVID have taken part in HEAL-COVID, a platform trial that is aiming to find treatments to reduce the number who die or are readmitted following their time in hospital.

In these first results from HEAL-COVID, it’s been shown that prescribing the oral anticoagulant Apixaban does not stop COVID patients from later dying or being readmitted to hospital over the following year (Apixaban 29.1%, versus standard care 30.8%).

As well as not being beneficial, anticoagulant therapy has known serious side effects, and these were experienced by participants in the trial with a small number of the 402 participants receiving Apixaban having major bleeding that required them to discontinue the treatment.

There was also no benefit from Apixaban in terms of the number of days alive and out of hospital at day 60 after randomization (Apixaban 59 days, versus standard care 59 days).

Following these results, the trial will continue to test another drug called Atorvastatin, a widely used lipid lowering drug (‘a statin’) that acts on other mechanisms of disease that are thought to be important in COVID.

Positive media coverage of cannabis studies regardless of therapeutic effect

Photo Credit: Julia Teichmann

In cannabis trials against pain, people who take placebos report feeling largely the same level of pain relief as those who consume the active cannabinoid substance. Still, these studies receive significant media coverage regardless of the clinical outcome, report researchers from Karolinska Institutet in Sweden in a study published in JAMA Network Open.

“We see that cannabis studies are often described in positive terms in the media regardless of their results,” says the study’s first author Filip Gedin, postdoc researcher at the Department of Clinical Neuroscience, Karolinska Institutet. “This is problematic and can influence expectations when it comes to the effects of cannabis therapy on pain. The greater the benefit a treatment is assumed to have, the more potential harms can be tolerated.”

The study is based on an analysis of published clinical studies in which cannabis has been compared with placebo for the treatment of clinical pain. The change in pain intensity before and after treatment were the study’s primary outcome measurement.

The analysis drew on 20 studies published up to September 2021 involving almost 1,500 individuals.

Discovery of antibody structure could lead to treatment for Crimean Congo Hemorrhagic Fever virus

Scott D. Pegan, a professor of biomedical sciences
Photo Source: University of California, Riverside

A research team led by the University of California, Riverside, has discovered important details about how therapeutically relevant human monoclonal antibodies can protect against Crimean Congo Hemorrhagic Fever virus, or CCHFV. Their work, which appears online in the journal Nature Communications, could lead to the development of targeted therapeutics for infected patients.

An emerging zoonotic disease with a propensity to spread, CCHF is considered a priority pathogen by the World Health Organization, or WHO. CCHF outbreaks have a mortality rate of up to 40%. Originally described in Crimea in 1944–1945, and decades later in the Congo, the virus has recently spread to Western Europe through ticks carried by migratory birds. The disease is already endemic in Africa, the Balkans, the Middle East, and some Asian countries. CCHFV is designated as a biosafety level 4 pathogen (the highest level of biocontainment) and is a Category A bioterrorism/biological warfare agent. There is no vaccine to help prevent infection and therapeutics are lacking.

Scott D. Pegan, a professor of biomedical sciences in the UCR School of Medicine, collaborated on this study with the United States Army Medical Research Institute of Infectious Diseases, or USAMRIID, which studies CCHFV because of the threat it poses to military personnel around the world. They examined monoclonal antibodies, or mAbs, which are proteins that bind to antigens — foreign substances that enter the body and cause the immune system to mount a protective response.

In a previous publication, USAMRIID scientists Joseph W. Golden and Aura R. Garrison reported that an antibody called 13G8 protected mice from lethal CCHFV when administered post-infection. They provided Pegan with the sequence information for that antibody, clearing the way for UCR to “humanize” it and conduct further research.

Localizing BRCA gene mutations to better treat ovarian cancer

Dr. Intidhar Labidi-Galy
Researcher at the Translational Research Centre in Onco-hematology at the UNIGE Faculty of Medicine and a physician at the HUG.
Credit: University of Geneva /  Intidhar Labidi-Galy

Mutations of BRCA1 and BRCA2 genes, which are inherited by 1 in 400 and 1 in 800 people respectively, significantly increase the risk of certain cancers such as ovarian, breast, pancreatic and prostate cancer. In 2016, a new class of drugs, the PARP inhibitors, was found to be highly effective against BRCA mutation-related tumors. However, almost half of women with ovarian cancer experience a recurrence of the disease within 5 years. An international team led by the University of Geneva (UNIGE), the Geneva University Hospitals (HUG), the Centre Léon Bérard in Lyon, the Curie Institute, the French collaborative group ARCAGY- GINECO and the European consortium ENGOT, examined the genetic data of 233 patients enrolled in the pre-marketing phase III clinical trial of olaparib, a PARP inhibitor added to bevacizumab, a drug already used to treat ovarian cancer. The researchers found that the success of PARP inhibitors depends on the precise location of the mutation on the gene. These results, that can be read in the journal Annals of Oncology, demonstrate that a very high precision medicine is possible in oncology.

The BRCA1 and BRCA2 genes code for proteins involved in the repair of DNA double-strand breaks, a particularly severe form of DNA damage, and thus play an essential role in maintaining the genomic stability of cells. When they are mutated, cells are less able to repair damaged DNA, a phenomenon that promotes the development of cancers.

Study sheds new light on the link between oral bacteria and diseases

Photo Credit: Quang Tri NGUYEN

Researchers at Karolinska Institutet have identified the bacteria most commonly found in severe oral infections. Few such studies have been done before, and the team now hopes that the study can provide deeper insight into the association between oral bacteria and other diseases. The study is published in Microbiology Spectrum.

Researchers at Karolinska Institutet have now analyzed samples collected between 2010 and 2020 at the Karolinska University Hospital in Sweden from patients with severe oral infections and produced a list of the most common bacteria.

This was a collaborative study that was performed by Professor Margaret Sällberg Chen and adjunct Professor Volkan Özenci’s research groups.

“We’re reporting here, for the first time, the microbial composition of bacterial infections from samples collected over a ten-year period in Stockholm County,” says Professor Sällberg Chen of the Department of Dental Medicine at Karolinska Institutet. “The results show that several bacterial infections with link to systemic diseases are constantly present and some have even increased over the past decade in Stockholm.”