Day: June 18, 2021

New Printable Biosensor Could Guide Surgery

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Surgeons may soon be able to pinpoint critical regions in tissues during surgery without interruption thanks to a new, 3D-printable biosensor.

Associate Professor Chi Hwan Lee created the biosensor, which enables both recording and imaging of tissues and organs during a surgical operation. Research on the biosensor was published in Nature Communications.

Prof Lee explained the benefits of such devices: “Simultaneous recording and imaging could be useful during heart surgery in localising critical regions and guiding surgical interventions such as a procedure for restoring normal heart rhythm.”

Existing methods to simultaneously record and image tissues and organs have proven challenging because other sensors used for recording typically interrupt the imaging process.

“To this end, we have developed an ultra-soft, thin and stretchable biosensor that is capable of seamlessly interfacing with the curvilinear surface of organs; for example the heart, even under large mechanical deformations, for example cardiac cycles,” Prof Lee said. “This unique feature enables the simultaneous recording and imaging, which allows us to accurately indicate the origin of disease conditions: in this example, real-time observations on the propagation of myocardial infarction in 3D.”

The biosensors are made of soft bio-inks and are rapid-prototyped to a custom-fit design, fitting a variety of sizes and shapes of an organ. The bio-inks used are softer than tissue, and can stretch without experiencing sensor degradation but also have reliable natural adhesion to the wet surface of organs without needing extra adhesives. The formulation and synthesis of the bio-inks was thanks to Kwan-Soo Lee’s research group in Los Alamos National Laboratory.

The researchers have produced a number of prototype biosensors using different shapes, sizes and configurations. Craig Goergen, the Leslie A Geddes Associate Professor of Biomedical Engineering in Purdue’s Weldon School of Biomedical Engineering, and his laboratory group have tested the prototypes in mice and pigs in vivo.

“Professor Goergen and his team were successfully able to identify the exact location of myocardial infarctions over time using the prototype biosensors,” Prof Lee said. “In addition to these tests, they also evaluated the biocompatibility and anti-biofouling properties of the biosensors, as well as the effects of the biosensors on cardiac function. They have shown no significant adverse effects.”

Source: Purdue University

Journal information: Kim, B., et al. (2021) Rapid custom prototyping of soft poroelastic biosensor for simultaneous epicardial recording and imaging. Nature Communications. doi.org/10.1038/s41467-021-23959-3.

In Vitro Cancer Cells Differ to Those in Body

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A new study has shown that most cancer cells grown in vitro have little in common genetically with cancer cells in humans.

Human cancer cells grown in culture dishes have the least genetic similarity to their human sources, according to a new computer-based technique developed by researchers at John Hopkins.

According to the researchers, the finding should help shift more resources to cancer research models such as genetically engineered mice and balls of human tissue known as ‘tumouroids’ to better evaluate human cancer biology and treatments, and the genetic errors responsible for cancer growth and progress.

“It may not be a surprise to scientists that cancer cell lines are genetically inferior to other models, but we were surprised that genetically engineered mice and tumouroids performed so very well by comparison,” says Patrick Cahan, PhD, associate professor of biomedical engineering at The Johns Hopkins University and the Johns Hopkins University School of Medicine and lead investigator of the new study.

The new computer modelling technique, CancerCellNet, compares the RNA sequences of a research model with data from a cancer genome atlas to see how closely the two sets match up.

On average, genetically engineered mice and tumouroids have RNA sequences most closely aligned with the genome atlas baseline data in 4 out of every 5 tumour types they tested, including breast, lung and ovarian cancers.

This adds to evidence that cancer cell lines grown in the laboratory have less parity with their human source due to the many differences between a human cell’s natural environment and a laboratory growth environment, the researchers said. “Once you take tumours out of their natural environment, cell lines start to change,” said Prof Cahan.

Around the world, scientists depend on a range of research models to enhance their understanding of cancer and other disease biology, and to develop treatments for conditions. Of these, one of the most widely used is cell lines created by extracting cells from human tumours and growing them with various nutrients in laboratory flasks.

Other methods involve mice that have been genetically engineered to develop cancer, or implanting human tumours into mice, known as xenografting, or use tumouroids.

To investigate the accuracy of these models, scientists often transplant lab-cultured cells or cells from tumouroids or xenografts into mice and see if the cells behave as they should — that is, grow and spread, retaining the genetic hallmarks of cancer. However, the researchers contend that this process is expensive, time-consuming and scientifically challenging and so they developed a more streamlined method. The new technique is based on genetic information about cellular RNA.

“RNA is a pretty good surrogate for cell type and cell identity, which are key to determining whether lab-developed cells resemble their human counterparts,” said Prof Cahan. “RNA expression data is very standardised and available to researchers, and less subject to technical variation that can confound a study’s results.”

To start, Prof Cahan and his team had to choose a standard set of data that acted as a baseline to compare the research models. They used data from The Cancer Genome Atlas as ‘training’ data, which includes RNA expression information of hundreds of patient tumour samples, and other information on the tumour.

They also tested their CancerCellNet tool by applying it to data where the tumour type was already known, such as from the International Human Genome Sequencing Consortium.

The John Hopkins researchers combed through The Cancer Genome Atlas data to select 22 types of tumours for study, and used that data as the baseline for comparing RNA expression data from cancer cell lines, xenografts, genetically engineered mouse models and tumouroids.

Some differences observed included prostate cancer cells from a line called PC3 that started to look genetically more like bladder cancer, Prof Cahan noted. It’s also possible, he said, that originally  the cell line was simply labelled incorrectly, or else it could have in fact been derived from bladder cancer. But, from a genetic standpoint, the prostate cancer cell line was not a representative surrogate for what happens in a typical human with prostate cancer.

According to a 0-1 scoring method, cell lines had, on average, lower scoring alignment to atlas data than tumouroids and xenografts.

Prof Cahan said he and his team will be improving the reliability of CancerCellNet by adding additional RNA sequencing data.

Source: John Hopkins Medicine

Journal information: Da Peng et al, Evaluating the transcriptional fidelity of cancer models, Genome Medicine (2021). DOI: 10.1186/s13073-021-00888-w

Beneficial Microbiota can be Restored at Birth in C-section Babies

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Babies born by caesarean section lack the same healthy bacteria as those born vaginally, but a Rutgers-led study for the first time finds that these natural bacteria can be restored.

The human microbiota, consisting of trillions of bacteria, viruses, fungi and other microorganisms, live in and on our bodies, some potentially harmful while others provide benefits. During labour and birth, women naturally impart a small group of colonisers to their babies’ sterile bodies, which helps their immune system to develop. But antibiotics and C-sections disrupt this conferring of microbes and are related to increased risks of obesity (59% increase), asthma (21% increase) and metabolic diseases. ‘Vaginal seeding‘, where a baby delivered by C-section is swabbed with their mother’s vaginal fluids at birth, is becoming increasingly popular.

According to the World Health Organization, C-section is needed in about 15 percent of births to avoid risking the life of the mother or child. However, caesarean birth rates continue to rise worldwide with recent (2016) reported rates of 24.5% in Western Europe, 32% in North America, and 41% in South America.

To see how well babies could be seeded with the mother’s microbiota after birth, the researchers followed 177 babies from four countries over the first year of their lives. Of these, 98 were born vaginally and 79 were born by C-section, 30 of which were swabbed with a maternal vaginal gauze right after birth.

Analysis showed that the microbiota of the C-section babies swabbed with their mother’s vaginal fluids was similar to that of vaginally born babies. Also, the mother’s vaginal microbiomes on the day of birth were similar to other areas of their bodies (gut, mouth and skin), indicating that maternal vaginal fluids help to colonise bacteria across their babies’ bodies.

This was the first large observational study to show that ‘vaginal seeding’ normalises the microbiome development during their first year of life. The next step would be conducting randomised clinical trials to determine if the microbiota normalisation translates into disease protection, the researchers said.

“Further research is needed to determine which bacteria protect against obesity, asthma and allergies, diseases with underlying inflammation,” said senior author Maria Gloria Dominguez Bello, a professor in the Department of Biochemistry and Microbiology in the School of Environmental and Biological Sciences at Rutgers University-New Brunswick. “Our results support the hypothesis that acquiring maternal vaginal microbes normalises microbiome development in the babies.”

Source: University News

COVID Shown to Damage The Testes

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Researchers at the University of Texas Medical Branch have discovered SARS-CoV-2 in the testes of infected hamsters, findings which may explain certain COVID symptoms reported in men.

Clinicians are finding that COVID affects more than just the lungs; some patients have reported testicular pain and some reports have shown decreases in testosterone. Autopsies have also shown evidence of significant disruption of the testes at the cellular level, severe in some cases, and presence of immune cells. Since SARS-CoV-2 has an affinity for ACE-2 receptors, and ACE-2 receptor expression is high in the testes, this could explain why this tissue becomes an infection target for COVID.

“Given the magnitude of the COVID pandemic, it is critical to investigate how this disease can impact the testes, and the potential consequences for disease severity, reproductive health and sexual transmission,” said Dr Rafael Kroon Campos, the study’s lead author and postdoctoral fellow in the laboratory of Dr Shannan Rossi at UTMB.

For a number of years, the Rossi lab had been studying Zika virus infection in the testes and wondered if SARS-CoV-2 could cause a similar disease. Hamsters are common models for COVID since they develop similar signs of disease to humans. Virus was detected in the testes of all infected hamsters during the first week but tapered off. The authors think this may represent what could occur in men with mild to moderate COVID disease.

“These findings are the first step in understanding how COVID impacts the male genital tract and potentially men’s reproductive health,” said Rossi, an associate professor in the Departments of Pathology and Microbiology & Immunology. “We have much more to do before we have the full picture. Moving forward, we will investigate ways to blunt this impact, including using antivirals, antibody therapies and vaccines.”

Future research could also include conditions associated with severe COVID, such as pre-existing conditions like obesity and diabetes and SARS-CoV-2 variants of concern, the study authors said.

Source: University of Texas Medical Branch at Galveston

Study Reveals Mediaeval Plague Victims Buried With Care and Attention

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Mediaeval plague victims in the UK were mostly buried with care and attention, according to a new study from Cambridge University. 

In the mid-14th century, Europe was devastated by the Black Death which killed between 40 and 60 per cent of the population. For centuries afterward, waves of plague would continue to strike the region.

Due to the rapid onset of death in the absence of antibiotic treatment (less than a week for bubonic plague and under 48h for pneumonic plague), the disease leaves no visible evidence on the skeleton, so until now archaeologists have been unable to identify individuals who died of plague unless they were buried in mass graves.

Although it has been long believed that most plague victims in fact received an individual burial, this has been impossible to confirm until now.

By studying DNA extracted from the teeth of individuals who died at this time, researchers from the Wellcome Trust-funded After the Plague project, based at the Department of Archaeology, University of Cambridge, have identified the presence of Yersinia Pestis, the bacterial pathogen that causes plague. The study is available to read online in the European Journal of Archaeology.

These include people who received normal individual burials at a parish cemetery and friary in Cambridge and in the nearby village of Clopton.

Lead author Craig Cessford of the University of Cambridge explained: “These individual burials show that even during plague outbreaks individual people were being buried with considerable care and attention. This is shown particularly at the friary where at least three such individuals were buried within the chapter house. The Cambridge Archaeological Unit conducted excavations on this site on behalf of the University in 2016-2017.”

The individual at the parish of All Saints by the Castle in Cambridge was also buried with care; this stand in contrast to the apocalyptic language used to describe the abandonment of this church in 1365 when it was reported that the church was partly in ruins and ‘the bones of dead bodies are exposed to beasts’.”

The study also shows that some plague victims in Cambridge did, as expected, receive mass burials.

Yersinia Pestis was also identified in several parishioners from St Bene’t’s, who were found buried together in a large trench in the churchyard excavated by the Cambridge Archaeological Unit on behalf of Corpus Christi College.

Soon afterwards, this part of the churchyard was transferred to Corpus Christi College, which was founded by the St Bene’t’s parish guild to commemorate the dead including the victims of the Black Death. For centuries, the members of the College would walk over the mass burial every day on the way to the parish church.

Cessford concluded, “Our work demonstrates that it is now possible to identify individuals who died from plague and received individual burials. This greatly improves our understanding of the plague and shows that even in incredibly traumatic times during past pandemics people tried very hard to bury the deceased with as much care as possible.”

Source: University of Cambridge

Journal information: “Beyond Plague Pits: Using Genetics to Identify Responses to Plague in Medieval Cambridgeshire” – Craig Cessford, Christiana L. Scheib, Meriam Guellil, Marcel Keller, Craig Alexander, Sarah A. Inskip and John E. Robb. European Journal of Archaeology, https://doi.org/10.1017/eaa.2021.19

SAMA Head Urges Stronger Lockdown; Two-thirds of Cases in Gauteng

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The South African Medical Association (SAMA) had said that early indications showed that the third wave of South Africa’s COVID pandemic would be worse than the previous two.

As infections surge around the country, particularly in Gauteng Province, the government  moved to Level 3, strengthening some curbs, including liquor sale restrictions, an extended curfew and a cap on the number of people allowed at gatherings. However, there has been no outright ban on alcohol.

As of Thursday, 11767 new COVID infections have been confirmed, with nearly two-thirds (7502) being recorded in Gauteng. The overall case positivity rate is 22.6%

SAMA chairperson Dr Angelique Coetzee said that the government’s measures were implemented far too late.

“People carry on as if everything is right. Everything is not right. We are in a pandemic, we are in a third wave and a third wave that’s going to be worse. At this stage, all the indications are that it is going to be worse than the second wave.”

Speaking to the SABC, she said Gauteng was running out of beds and oxygen. “If you want a bed in Gauteng you are going to struggle so this is what we’re seeing and if we want to get out of this we need to make tough decisions. But it seems like it’s not going to happen so for now it is what it is and no one should be astonished if the numbers go up,” says Coetzee.

Dr Coetzee also warned that allowing schools to remain open was a bad decision.

“Without proper, effective and decisive measures to curb the spread of COVID, our infection and fatality numbers are going to climb even further. In addition, schools are still open, travel is still allowed and public transport can still operate as they currently are. This should not have been allowed.”

The Basic Education Department had already dismissed suggestions that schools should be closed as well as part of the COVID containment efforts. She also argued against a  simple tightening of curfews and alcohol sales.

“Nothing significant has changed. The stricter curfew measures and limitations on alcohol sales will simply mean people change their behaviour to accommodate for these restrictions and will have little impact on people’s daily routines. This is actually where restrictions should have been targeted.”

Speaking to Jacaranda, she said, “For us, it doesn’t make sense, we need people at home. We don’t want people in a shopping centre or anywhere else, if we can manage to do that for three to four weeks we can get the numbers down but for now, I don’t see that happening.”

Source: EWN