Set up reserve lab capacity now for faster response to next pandemic, say researchers

Female scientist in laboratory 
Photo credit: Diane Serik

The researchers, who were on the front line of the UK’s early response to COVID-19 in 2020, say a system of reservist lab scientists should to be set up now to provide surge capacity that will help the country respond faster – and more effectively – to future outbreaks of infectious disease.

They considered a number of options for providing scientific surge capacity and concluded that the best scenario would be a mix of highly skilled paid reservists, and volunteers who could be called on when required and trained rapidly.

In their report, published today in the journal The BMJ, the researchers say the lack of early COVID-19 PCR testing capacity had a knock-on effect on other health services in 2020. This included delaying the ability to make sure hospitals were COVID-secure and patients had surgery as safely as possible, and slowing down the identification of people with COVID-19 in the community – which delayed contact tracing.

“Because COVID-19 testing wasn’t scaled up quickly enough, we couldn’t detect all cases quickly enough to try and stop the spread of the disease,” said Dr Jordan Skittrall in the University of Cambridge’s Department of Pathology and first author of the report.

“It was frustrating to hear politicians’ promises to repeatedly scale up COVID-19 testing capacity during the early stage of the pandemic. The scale-up was extremely challenging: a lot of expertise is needed to get the tests working in the early stages of dealing with a new pathogen,” he added.

No difference between spinal versus general anesthesia in patients having hip fracture surgery

Image credit: Fernando zhiminaicela

There are no differences in the safety or effectiveness of the two most common types of anesthetics (spinal versus general anesthesia) in patients undergoing hip fracture surgery, according to the findings of a new study led by the University of Bristol in collaboration with University of Warwick researchers. The findings, published in the British Journal of Anesthesia, analyzed previously published data on nearly 4,000 hip fracture patients.

The research was funded by The Academy of Medical Sciences and supported by the NIHR Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol.

Hip fractures are devastating injuries and remain one of the largest healthcare challenges of the twenty-first century. The incidence increases with advancing age and the number of hip fractures is expected to rise to 6.26 million per year in 2050. In 2017, hip fractures cost the National Health Service (NHS) over £1 billion, which is projected to increase to £5.6 billion in 2033. Patients with hip fractures have a relatively high risk of dying within a year of their injury.

Almost all patients with a hip fracture undergo surgery, requiring anesthesia to be performed so that surgery is safe and not painful. Nearly all patients will receive either spinal or general anesthesia. Given the risk profile of hip fracture patients (older age, frailty, and comorbidities like cardiac and respiratory diseases), surgery is associated with a high risk of developing post-operative complications including delirium, myocardial infarction, pneumonia, stroke, and death.

Is SARS-CoV-2 hiding in your fat cells?

Left: Catherine Blish, MD, PhD, professor of infectious diseases. Right: Tracey McLaughlin, MD, professor of endocrinology.
Source: Stanford Medicine | Stanford University

A study by Stanford Medicine investigators shows that SARS-CoV-2 can infect human fat tissue. This phenomenon was seen in laboratory experiments conducted on fat tissue excised from patients undergoing bariatric and cardiac surgeries, and later infected in a laboratory dish with SARS-CoV-2. It was further confirmed in autopsy samples from deceased COVID-19 patients.

Obesity is an established, independent risk factor for SARS-CoV-2 infection as well as for the patients’ progression, once infected, to severe disease and death. Reasons offered for this increased vulnerability range from impaired breathing resulting from the pressure of extra weight to altered immune responsiveness in obese people.

But the new study provides a more direct reason: SARS-CoV-2, the virus that causes COVID-19, can directly infect adipose tissue (which most of us refer to as just plain “fat”). That, in turn, cooks up a cycle of viral replication within resident fat cells, or adipocytes, and causes pronounced inflammation in immune cells that hang out in fat tissue. The inflammation even converts uninfected “bystander” cells within the tissue into an inflammatory state.

Shutting down backup genes leads to cancer remission in mice

Abhinav Achreja, PhD, Research Fellow at the University of Michigan Biomedical Engineering and Deepak Nagrath, Ph.D. Associate Professor of Biomedical Engineering works on ovarian cancer cell research in the bio-engineering lab at the North Campus Research Center (NCRC).
Image credit: Marcin Szczepanski, Michigan Engineering

The way that tumor cells enable their uncontrolled growth is also a weakness that can be harnessed to treat cancer, researchers at the University of Michigan and Indiana University have shown.

Their machine-learning algorithm can identify backup genes that only tumor cells are using so that drugs can target cancer precisely.

“Most cancer drugs affect normal tissues and cells. However, our strategy allows specific targeting of cancer cells.”

Deepak Nagrath

The team demonstrated this new precision medicine approach for treating ovarian cancer in mice. Moreover, the cellular behavior that exposes these vulnerabilities is common across most forms of cancer, meaning the algorithms could provide better treatment plans for a host of malignancies.

“This could revolutionize the precision medicine field because the drug targeting will only affect and kill cancer cells and spare the normal cells,” said Deepak Nagrath, a U-M associate professor of biomedical engineering and senior author of the study in Nature Metabolism. “Most cancer drugs affect normal tissues and cells. However, our strategy allows specific targeting of cancer cells.”

Newly Discovered Barrier Prevents Immunity from Reaching Smell-Sensing Cells

Circulating antibody (white) is prevented from accessing olfactory epithelium (green) by a previously unknown blood-olfactory barrier, the BOB.
Credit: Ashley Moseman Lab, Duke University

Duke scientists have identified a previously unknown barrier that separates the bloodstream from smelling cells in the upper airway of mice, likely as a way to protect the brain.

But this barrier also ends up keeping some of the larger molecules of the body’s immune system out, and that may be hindering the effectiveness of vaccines.

It makes sense to have a protective barrier for the olfactory cells lining the nose, because they offer a direct path to the olfactory bulb of the brain, making them effectively extensions of the brain itself, said lead researcher Ashley Moseman, an assistant professor of immunology in the Duke School of Medicine.

However, the new barrier, which his team has dubbed the BOB – the blood-olfactory barrier -- also might be keeping vaccines against respiratory viruses from being more effective by preventing those antibodies from reaching the mucous on the surface of the nose, the first barrier a virus encounters.

The team was trying to understand better how the immune system protects the upper respiratory tract by infecting mice with a virus called vesicular stomatitis virus, or VSV, that is known to penetrate to the central nervous system. Once inhaled, VSV readily infects the olfactory sensing cells and rapidly replicates, reaching the olfactory bulb of the brain within a day. Although it can lead to paralysis and death, it is usually cleared by a T cell response.

Risk of blood clots remains for almost a year after COVID-19 infection, study suggests

Credit: pixabay

COVID-19 infection increases the risk of potentially life-threatening blood clots for at least 49 weeks, according to a new study of health records of 48 million unvaccinated adults from the first wave of the pandemic.

The findings suggest that the COVID-19 pandemic may have led to an additional 10,500 cases of heart attacks, strokes and other blood clot complications such as deep vein thrombosis in England and Wales in 2020 alone, although the excess risk to individuals remains small and reduces over time.

The research – involving a large team of researchers led by the Universities of Bristol, Cambridge, and Edinburgh, and Swansea University – shows that people with only mild or moderate disease were also affected. The authors suggest that preventive strategies, such as giving high-risk patients medication to lower blood pressure, could help reduce cases of serious clots.

Researchers studied de-identified electronic health records across the whole population of England and Wales from January to December 2020 to compare the risk of blood clots after COVID-19 with the risk at other times. Data were accessed securely and safely via the NHS Digital Trusted Research Environment for England, and the SAIL Databank for Wales.

In the first week after a COVID-19 diagnosis, people were 21 times more likely to have a heart attack or stroke, conditions which are mainly caused by blood clots blocking arteries. This dropped to 3.9 times more likely after 4 weeks.

Discovery explains cancer chemotherapy resistance, offers solution

 Experimental DNA fibers with fluorescence (pictured) were used to reveal the speed of DNA replication forks.
Credit: Diego Dibitetto/Smolka Lab

Researchers have uncovered a novel pathway that explains how cancer cells become resistant to chemotherapies, which in turn offers a potential solution for preventing chemo-resistance.

The study, “DNA-PKcs Promotes Fork Reversal and Chemoresistance,” was published Sept. 20 in the journal Molecular Cell.

The research describes for the first time how a type of enzyme – previously known for its roles in DNA repair – prevents DNA damage in cancer cells, making them tolerant to chemotherapy drugs.

“It provides us tools to manipulate and then break chemo-resistance in cancer cells,” said Marcus Smolka, interim director of the Weill Institute for Cell and Molecular Biology and professor of molecular biology and genetics in the College of Agriculture and Life Sciences. Diego Dibitetto, a former postdoctoral researcher in Smolka’s lab who is currently at the University of Bern in Switzerland, is the paper’s first author.

Many anti-cancer drugs work by creating blocks on the DNA of cancer cells as they replicate. During replication, DNA strands entwined in a double helix separate into two individual strands so each strand can be copied, eventually leading to two new double helixes. The junction where this separation and copying occurs is called a replication fork, which unzips down the double helix.

Statin use is not justified for healthy people with high cholesterol

Professor David Diamond, Department of Psychology
Credit: University of South Florida

About 40 million adults in the United States regularly take statins to lower their cholesterol levels and reduce their risk of heart disease and stroke, according to American Heart Association data from 2020.

However, many of them don’t stand to benefit from these drugs based on new research from David Diamond, a neuroscientist and cardiovascular disease researcher in the Department of Psychology at the University of South Florida.

Diamond and his co-authors reviewed literature from medical trials involving patients taking either a statin or placebo. They then narrowed their review to look at study participants with elevated levels of low-density lipoprotein-cholesterol (LDL), the so-called “bad cholesterol,” which can be reduced with a statin. Some individuals with high LDL also had high triglycerides (fat in the blood) and low high-density lipoprotein (HDL), the “good cholesterol,” which put them at the highest risk of having a heart attack.

But others with high LDL were very different. They had low triglycerides and high HDL, which meant they were healthier. People with optimal triglycerides and HDL levels typically exercise, have low blood pressure and low blood sugar, and are at a low risk of a heart attack.

Diamond and his co-authors asked two questions: If people are at a low risk of a heart attack based on having optimal triglycerides and HDL, but they also have high LDL, does that raise their risk? Further, would these people benefit from lowering their LDL with a statin?

Laser light offers new tool for treating bone cancer

Left: An image of cancerous tissue prepared with the traditional hematoxylin and eosin (H&E) staining method. Right: An image of cancerous tissue prepared with the UV-PAM method. The results are very similar to those produced with the H&E method, but are ready much faster.
Credit: Caltech

Label-free intraoperative histology of bone tissue via deep-learning-assisted ultraviolet photoacoustic microscopy of the many ways to treat cancer, the oldest, and maybe most tried and true, is surgery. Even with the advent of chemotherapy, radiation therapy, and more experimental treatments like bacteria that seek and destroy cancer cells, cancers, very often, simply need to be cut out of a patient's body.

The goal is to remove all of the cancerous tissue while preserving as much of the surrounding healthy material as possible. But because it can be difficult to draw a clean line between cancerous and healthy tissues, surgeons often err on the side of caution and remove healthy tissue to make sure they have taken out all of the cancerous tissue.

This is especially problematic when a patient is suffering from a cancer that afflicts bones; bones present unique challenges during surgery because of how hard they are compared with other tissues and because they grow back much more slowly than other kinds of tissue.

Exercise may be key to developing treatments for rare movement disorders

Spinal cerebellar ataxia 6 (SCA6) is an inherited neurological condition which has a debilitating impact on motor coordination. Affecting around 1 in 100,000 people, the rarity of SCA6 has seen it attract only limited attention from medical researchers. To date, there is no known cure and only limited treatment options exist.

Now, a team of McGill University researchers specializing in SCA6 and other forms of ataxia, have published findings that not only offer hope for SCA6 sufferers but may also open the way to developing treatments for other movement disorders.

Exercise in a pill

In mice affected by SCA6, the McGill team, led by biology professor Alanna Watt, found that exercise restored the health of cells in the cerebellum, the part of the brain implicated in SCA6 and other ataxias. The reason for the improvement, the researchers found, was that exercise increased levels of brain-derived neurotrophic factor (BDNF), a naturally occurring substance in the brain which supports the growth and development of nerve cells. Importantly for patients with a movement disorder, for whom exercise may not always be feasible, the team demonstrated that a drug that mimicked the action of BDNF could work just as well as exercise, if not better.

New wearable device measures the changing size of tumors below the skin

The FAST system measures tumor size regression and is a new way to test the efficacy of cancer drugs.
  Image credit: Alex Abramson, Bao Group, Stanford University

Electronically sensitive, skin-like membrane can measure changes in tumor size to the hundredth of a millimeter. It represents a new, faster, and more accurate approach to screen cancer drugs.

Engineers at Stanford University have created a small, autonomous device with a stretchable and flexible sensor that can be adhered to the skin to measure the changing size of tumors below. The non-invasive, battery-operated device is sensitive to one-hundredth of a millimeter (10 micrometers) and can beam results to a smartphone app wirelessly in real time with the press of a button.

In practical terms, the researchers say, their device – dubbed FAST for “Flexible Autonomous Sensor measuring Tumors” – represents a wholly new, fast, inexpensive, hands-free, and accurate way to test the efficacy of cancer drugs. On a grander scale, it could lead to promising new directions in cancer treatment. FAST is detailed in a paper published Sept. 16 in Science Advances.

Each year researchers test thousands of potential cancer drugs on mice with subcutaneous tumors. Few make it to human patients, and the process for finding new therapies is slow because technologies for measuring tumor regression from drug treatment take weeks to read out a response. The inherent biological variation of tumors, the shortcomings of existing measuring approaches, and the relatively small sample sizes make drug screenings difficult and labor-intensive.

Higher risk of serious COVID-19 complications in children with immunodeficiency

Qiang Pan Hammarström, professor at Karolinska Institutet.
Photo credit: Erik Flyg.

Children with certain immunodeficiency diseases carry mutations in genes that regulate the body’s immune system against viral infections and they have a higher mortality rate due to COVID-19. This is according to a study by researchers from Karolinska Institutet, published in the Journal of Allergy and Clinical Immunology (PDF).

Most children infected with the SARS-CoV-2 coronavirus develop a mild illness or show no symptoms at all. But for a small percentage, serious complications may develop.

“Mortality is much higher among children with primary immunodeficiency diseases infected with SARS-CoV-2. Our results indicate that basic immunological examination and genetic analysis should be conducted in children with severe COVID-19 or multi-inflammatory syndrome (MIS-C). The clinicians will then be able to help these children with more precise therapies based on their genetic changes,” says Qiang Pan-Hammarström, professor at the Department of Biosciences and Nutrition, Karolinska Institutet, who led the study.

How the infection affects patients with primary immunodeficiency diseases, i.e. hereditary and congenital diseases of the immune system, is controversial. Even among these patients, some suffer from severe COVID-19 while others experience mild or no symptoms.

Cells from miniature pigs are paving the way for improved stem cell therapies.

A breed of pigs called Wisconsin Miniature Swine — created by a team of UW–Madison scientists — will help researchers better model and understand human diseases.
Credit: Jeff Miller

A team led by University of Wisconsin–Madison Stem Cell & Regenerative Medicine Center researcher Wan-Ju Li offers an improved way to create a particularly valuable type of stem cell in pigs – a cell that could speed the way to treatments that restore damaged tissues for conditions from osteoarthritis to heart disease in human patients.

In a study published in Scientific Reports, Li’s team also provides insights into the reprogramming process that turns cells from one part of the body into pluripotent stem cells, a type of building block cell that can transform into any type of tissue. These new insights will help researchers study treatments for a wide range of diseases.

The researchers turned to pigs, a well-established animal model for potential human treatments, because translating research to improve human health is deeply important to Li, a professor of Orthopedics and Rehabilitation and Biomedical Engineering. He has spent much of his career studying cartilage and bone regeneration to develop innovative therapies to help people.

Li and members of his Musculoskeletal Biology and Regenerative Medicine Laboratory obtained skin cells from the ears of three different breeds of miniature pigs — Wisconsin miniature swine, Yucatan miniature swine and Göttingen minipigs.

Airway antibodies protect against omicron infection

Charlotte Thålin, assistant chief physician and associate professor at Department of Clinical Sciences, Danderyds Hospital, Karolinska Institutet, led the study.
Credit: Ludvig Costyal

High levels of antibodies in the airways reduce the risk of being infected by omicron, but many do not receive measurable antibody levels in the airways desperate three doses of SARS-Cov-2 vaccine. It shows a new study published in The New England Journal of Medicine by researchers at Karolinska Institutet and Danderyds Hospital.

The COMMUNITY study started in the spring of 2020 with a provincial collection of 2,149 employees at Danderyds Hospital. The study participants and their immune response to the coronavirus sars-cov-2 have since followed up every four months. At the beginning of 2022, a study was conducted in which 338 employees who received three doses of vaccine were regularly screened for SARS-Cov-2 infection. Of those who were not infected at the start of the study, sixth participants (57 people) were infected with omics during the course of the study. This allowed the research team to investigate what protects against infection and what the immune response after omicron infection looks like.

These pesticides may increase cancer risk in children

Julia Heck, associate research professor of epidemiology
in the UCLA Fielding School of Public Health.
Source: UCLA

Past research has shown that pesticide exposure increases the risk of cancer. Now, UCLA-led research has exposed which specific pesticides increase the risk of retinoblastoma — a rare eye tumor — in children.

The study, published in the August International Journal of Hygiene and Environmental Health, found that children prenatally exposed to the chemicals acephate and bromacil had an increased risk of developing unilateral retinoblastoma, or cancer in one eye, and that exposure to pymetrozine and kresoxim-methyl increased the risk of all types of retinoblastoma.

“What’s important is looking at specific bad actors and identifying them,” said Julia Heck, an adjunct associate professor in the department of epidemiology at the UCLA Fielding School of Public Health, who studies environmental causes of childhood cancers.

Identifying specific pesticides correlated with cancer is the first step toward banning or replacing them with less harmful options.

The researchers studied land use data and pesticide use reports — which provide information on where, when and in what quantity the chemicals are applied — to determine locations of possible pesticide exposure. They considered 132 pesticides that are associated with cancer.

They compared children with retinoblastoma to random children with California birth certificates and found that those with cancer were more likely to have been born in neighborhoods near applications of specific pesticides.

Study finds white children more likely to be overdiagnosed for ADHD

A new study by Professor Paul Morgan finds that white children are more likely to be overdiagnosed for ADHD than children of color.
Photo credit: Ben White on Unsplash

A new study led by Paul Morgan, Harry and Marion Eberly Faculty Fellow and professor of education (educational theory and policy) and demography, and published in the Journal of Learning Disabilities, examines which sociodemographic groups of children are more likely to be overdiagnosed and overtreated for ADHD. The researchers analyzed data from 1,070 U.S. elementary school children who had previously displayed above-average behavioral, academic or executive functioning the year before their initial ADHD diagnoses. The team said those children were considered unlikely to have ADHD by the researchers because children diagnosed and treated for ADHD should displaychronically inattentive, hyperactive or impulsive behaviors that impair their functioning and result in below-average academic or social development.

A problem with ADHD overdiagnosis, Morgan said, is that it contributes to stigma and skepticism toward those experiencing more serious impairments.

“It undermines a confidence in the disorder,” he said. “If anyone can be diagnosed with ADHD, then what is ADHD? For those who have significant impairments, they may experience greater skepticism about the condition. Mental health resources are already scarce, those with serious impairments could lose out.”

Ural Scientists Develop Technology to Correct Genetic Defects

According to Mikhail Bolkov, a regulatory framework is also needed for genetic intervention therapy. Photo credit: Ilya Safarov

Scientists at the Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences and UrFU develop methods for genetic diagnosis and therapy of diseases caused by primary immunodeficiency. This is a congenital malfunction of one or more parts of the immune system that predisposes to the development of frequent, prolonged, hard-to-treat diseases, not only infectious but also autoimmune, autoinflammatory and oncological diseases. For example, systemic lupus erythematosus, various vasculitis, chronic pneumonia, and even hair loss.

Today, primary immunodeficiencies are treated with replacement therapy and hematopoietic stem cell transplantation. However, the treatment of such diseases promises to become more effective by replacing genetic defects in human DNA. Mikhail Bolkov, a Senior Researcher at the Department of Immunochemistry of Ural Federal University and the Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences, spoke about this on the air of Radio "Komsomolskaya Pravda".

New knowledge about the link between infection during pregnancy and autism

Credit: Mart Production

Infections in pregnant women have been linked to increased risk of neuropsychiatric conditions, such as autism, in the child later in life. But it does not appear to be the infections themselves that cause autism, researchers from Karolinska Institutet show in a study published in The Lancet Psychiatry.

Our results can reassure future parents by showing that infections during pregnancy may not pose as much risk to the child's brain as previously thought, say Håkan Karlsson, researchers at Department of Neuroscience at Karolinska Institutet and the study's last author.

Previous studies have shown a link between infections of the future mother during pregnancy and increased risk of autism and intellectual disability in the child later in life.

But they have not been able to say whether it is really the infection of the mother that is the cause, or whether other factors are behind it. Researchers from Karolinska Institutet have now studied this more closely.

Elevated Cholesterol Found in GenX Exposure Study Participants

Photo credit: Luis Tosta on Unsplash

In a new paper detailing findings from North Carolina State University’s GenX Exposure Study, researchers found that elevated levels of per- and polyfluoroalkyl substances (PFAS) were associated with higher total cholesterol and non-HDL cholesterol in participants’ blood. They also found that the legacy PFAS chemicals PFOS and PFNA were most strongly associated with elevated cholesterol compared to the other chemicals, and that the effects were more pronounced in older people.

“Previous studies had established links between PFAS and elevated cholesterol,” says Jane Hoppin, professor of biological sciences, director of NC State’s Center for Human Health and the Environment (CHHE), member of NC State’s Center for Environmental and Health Effects of PFAS, and corresponding author of the paper describing the work. “However, most of the previous work had focused on PFOA and PFOS, though we know that people are exposed to many other chemicals in the PFAS family. So, we wanted to look not just at legacy PFAS, but also at certain fluoroethers, a family of chemicals that include GenX and that have similar chemical structure to PFAS.”

The blood samples came from 344 Wilmington residents (289 adults and 55 children) across two sampling efforts in November 2017 and May 2018.

More than 10 million children were affected by COVID-19-associated parental and caregiver deaths

According to a new modeling study, published in JAMA Pediatrics, the number of children estimated to have experienced the death of a parent or caregiver as a result of the COVID-19 pandemic has climbed to more than 10.5 million globally as of May 1, 2022.

The new study, involving the University of Oxford, Imperial College, the African Institute for Mathematical Sciences, the Centers for Disease Control and Prevention (CDC), and the World Health Organization (WHO), builds on the best available and most conservative data recently published by WHO on excess COVID-19 deaths (14.9 million as of Dec 31, 2021), to establish estimates of orphaned children in every country. This is the first-time availability of these comprehensive data on excess deaths for every country, and it enabled the data modelers to update global minimum estimates of pandemic orphanhood and caregiver death among children based on these excess deaths.

Excess deaths are typically defined as the difference between the observed numbers of deaths in specific time periods and expected numbers of deaths in the same time periods. Estimates of excess deaths can provide information about the burden of mortality potentially related to the COVID-19 pandemic, including deaths that are directly or indirectly attributed to COVID-19.

In this study, authors analyzed country-level deaths, fertility rates, and national excess mortality data provided by the WHO, the Economist, and the Institute for Health Metrics and Evaluation, and used mathematical modelling to develop global estimates based on the WHO estimates, which were the most conservative.