An Australian study published in PLOS Biologysuggests the nasal epithelium of children inhibits infection and replication of the ancestral strain of the SARS-CoV-2 virus and also the Delta variant, but not the Omicron variant.
Children are in general less susceptible to COVID, with a lower infection rate and milder symptoms than adults. However, the factors driving this apparent paediatric resistance to COVID infections remained unknown.
In order to better understand infection and replication of SARS-CoV-2 in children, Kirsty Short at University of Queensland, and colleagues, obtained samples of primary nasal epithelium cells from twenty-three healthy children aged 2–11 and fifteen healthy adults aged 19–66 in Australia. They exposed the cells of adults and children to SARS-CoV-2 and then observed the infection kinetics and antiviral responses in children compared to adults.
The researchers found that ancestral SARS-CoV-2 replicated less efficiently and was associated with a heightened antiviral response in the nasal epithelial cells of children. This lower viral replication rate was also observed with the Delta variant, but not the Omicron variant.
Study limitations included a small sample size, so future clinical studies will be needed to validate these preliminary findings in a larger population and to determine the role of other factors, such as antibodies in protecting children from SARS-CoV-2 infection. Additionally, paediatric protection from emerging variants has yet to be quantified.
The authors wrote, “We have provided the first experimental evidence that the paediatric nasal epithelium may play an important role in reducing the susceptibility of children to SARS-CoV-2. The data strongly suggest that the nasal epithelium of children is distinct and that it may afford children some level of protection from ancestral SARS-CoV-2.”
Short added, “We use nasal epithelial cells from children and adults to show that the ancestral SARS-CoV-2 and Delta, but not Omicron, replicate less efficiently in paediatric nasal epithelial cells.”
Part of the higher risk of cardiovascular disease associated with red meat consumption could be from metabolites produced by gut microbes, suggests new research published in Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB).
“Most of the focus on red meat intake and health has been around dietary saturated fat and blood cholesterol levels,” said co-lead author of the study Meng Wang, PhD. “Based on our findings, novel interventions may be helpful to target the interactions between red meat and the gut microbiome to help us find ways to reduce cardiovascular risk.”
Previous research has found that certain metabolites are associated with a greater risk of cardiovascular disease. One of these is trimethylamine N-oxide (TMAO), which is produced by gut bacteria to digest red meat that contains high amounts of the chemical L-carnitine.
High blood levels of TMAO in humans may be linked to increased risks of CVD, chronic kidney disease and Type 2 diabetes. However, whether TMAO and L-carnitine-derived metabolites was linked to cardiovascular disease and to what extent, are still unknown.
To find out, the study researchers measured levels of the metabolites in blood samples. They also examined whether blood sugar, inflammation, blood pressure and blood cholesterol may account for the elevated cardiovascular risk associated with red meat consumption.
Study participants included nearly 4000 of the 5888 adults initially recruited from 1989 to 1990 for the Cardiovascular Health Study (CHS). The participants selected for the current study were free of clinical cardiovascular disease at time of enrolment in the CHS, an observational study of risk factors for cardiovascular disease in adults aged 65 or older. The CHS follows 5 888 participants, whose average age at enrolment was 73; nearly two-thirds were female and 88% of participants self-identified as white. The median follow-up time for participants was 12.5 years, and up to 26 years in some cases. At follow-up appointment, participants’ medical history, lifestyle, health conditions and sociodemographic characteristics were assessed.
Several blood biomarkers were measured at the start of the study and again in 1996–1997. The fasting blood samples stored frozen at -80°C were tested for levels of several gut-microbiome linked to red meat consumption including TMAO, gamma-butyrobetaine and crotonobetaine.
Additionally, all study participants answered two validated food-frequency questionnaires about their usual dietary habits, including intake of red meat, processed meat, fish, poultry and eggs, at the start of the study and again from 1995 to 1996. For the first questionnaire, participants indicated how often, on average in the previous 12 months, they had eaten given amounts of various foods, ranging from “never” to “almost every day or at least five times per week,” based on medium portion sizes, which varied based on the food source. The second questionnaire used a ten-category frequency of average intake over the past 12 months, ranging from “never or less than once per month” to “six+ servings per day,” with defined standard portion sizes.
For the current analyses, the researchers compared the risk of cardiovascular disease among participants who ate different amounts of animal source foods (ie, red meat, processed meat, fish, chicken and eggs). They found that eating more meat, especially red meat and processed meat, was linked to a higher risk of atherosclerotic cardiovascular disease, an increased risk of 22% for 1.1 serving per day.
The increase in TMAO and related metabolites explained roughly one-tenth of this elevated risk, the authors said. They also noted that blood sugar and general inflammation pathways may help explain the links between red meat intake and cardiovascular disease. Blood sugar and inflammation also appear to be more important in linking red meat intake and cardiovascular disease than pathways related to blood cholesterol or blood pressure. Intake of fish, poultry and eggs were not significantly linked to higher risk of cardiovascular disease.
“Research efforts are needed to better understand the potential health effects of L-carnitine and other substances in red meat such as heme iron, which has been associated with Type 2 diabetes, rather than just focusing on saturated fat,” Dr Wang said.
Researchers have shown a direct link between vagus nerve stimulation and its connection to the brain’s learning centres. The discovery, reported in the journal Neuron, may lead to treatments that will improve cognitive retention in both healthy and injured nervous systems.
“We concluded that there is a direct connection between the vagus nerve, the cholinergic system that regulates certain aspects of brain function, and motor cortex neurons that are essential in learning new skills,” said Cristin Welle, PhD, senior author of the paper. “This could provide hope to patients with a variety of motor and cognitive impairments, and someday help healthy individuals learn new skills faster.”
Researchers taught healthy mice a difficult task to see if it could help boost learning. Stimulating the vagus nerve during the process was found to help the mice learn the task much faster and achieve a higher performance level. This showed that vagus nerve stimulation can increase learning in a healthy nervous system.
The vagus nerve regulates internal organ functions like digestion, heart rate and respiration, as well as helping control reflex actions like coughing and sneezing.
The study also revealed a direct connection between the vagus nerve and the cholinergic system, which is essential for learning and attention. Each time the vagus nerve was stimulated, researchers could observe the neurons that control learning activated within the cholinergic system. Damage to this system has been linked to Alzheimer’s disease, Parkinson’s disease and other motor and cognitive conditions. Now that this connection has been established in healthy nervous systems, Dr Welle said it could lead to better treatment options for those whose systems have been damaged.
“The idea of being able to move the brain into a state where it’s able to learn new things is important for any disorders that have motor or cognitive impairments,” she said. “Our hope is that vagus nerve stimulation can be paired with ongoing rehabilitation in disorders for patients who are recovering from a stroke, traumatic brain injury, PTSD or a number of other conditions.”
In addition to the study, Dr Welle and her team have applied for a grant that would allow them to use a non-invasive device to stimulate the vagus nerve to treat patients with multiple sclerosis who have developed movement deficits. She also hopes that this device could eventually help speed up skill learning in healthy people.
“I think there’s a huge untapped potential for using vagus nerve stimulation to help the brain heal itself,” she said. “By continuing to investigate it, we can ultimately optimise patient recovery and open new doors for learning.”
Genetic mutations behind a genetic kidney disease affecting children and young adults have been fixed in patient-derived kidney cells with a high-capacity DNA ‘repair kit’. The advance, developed by University of Bristol scientists, is published in Nucleic Acids Research.
In this new study, the international team describe how they created a DNA repair vehicle to genetically fix faulty podocin, a common genetic cause of inheritable Steroid Resistant Nephrotic Syndrome (SRNS).
Podocin is a protein normally located on the surface of specialised kidney cells and is essential for kidney function. Faulty podocin, however, remains stuck inside the cell and never makes it to the surface, terminally damaging the podocytes. Since the disease cannot be cured with medications, gene therapy which repairs the genetic mutations causing the faulty podocin offers hope for patients.
Typically, human viruses have been utilised in gene therapy applications to carry out genetic repairs. These are used as a ‘Trojan Horse’ to enter cells carrying the errors. Currently dominating systems include lentivirus (LV), adenovirus (AV) and adeno-associated virus (AAV), which are all relatively harmless viruses that readily infect humans. Their viral shells however restrict the amount of cargo they can carry and deliver, namely the DNA kit necessary for efficient genetic repair. This limits the scope of their application in gene therapy.
By applying synthetic biology techniques, the team led by Dr Francesco Aulicino and Professor Imre Berger, re-engineered baculovirus, a insect virus which has a nearly unlimited cargo capacity.
“What sets apart baculovirus from LV, AV, and AAV is the lack of a rigid shell encapsulating the cargo space.” said Dr Francesco Aulicino, who led the study. The shell of baculovirus resembles a hollow stick, simply lengthening when the cargo increases. This allows a much more sophisticated tool-kit can be delivered by the baculovirus.
First, baculovirus had to be equipped to penetrate human cells which it normally would not do. “We decorated the baculovirus with proteins that enabled it to enter human cells very efficiently.” explained Dr Aulicino. The scientists then used their engineered baculovirus to deliver much larger DNA pieces than was previously possible, and build these into the genomes of a whole range of human cells.
The DNA in the human genome comprises 3 billion base-pairs making up ~25,000 genes, which encode for the proteins that are essential for cellular functions. If faulty base-pairs occur in our genes, faulty proteins are made which can make us ill, resulting in hereditary disease. Gene therapy promises repair of hereditary disease at its very root, by rectifying such errors in our genomes. Gene editing approaches, in particular CRISPR/Cas-based methods, have greatly advanced the field by enabling genetic repair with base-pair precision.
The team used patient-derived podocytes carrying the disease-causing error in the genome to demonstrate the aptitude of their technology. By creating a DNA repair kit, comprising protein-based scissors and the nucleic acid molecules that guide them – and the DNA sequences to replace the faulty gene, the team delivered with a single engineered baculovirus a healthy copy of the podocin gene concomitant with the CRISPR/Cas machinery to insert it with base-pair precision into the genome. This was able to reverse the disease-causing phenotype and restore podocin to the cell surface.
Professor Imre Berger explained: “We had previously used baculovirus to infect cultured insect cells to produce recombinant proteins for studying their structure and function.” This method, called MultiBac, has been highly successful to make very large multiprotein complexes with many subunits, in laboratories world-wide. “MultiBac already exploited the flexibility of the baculovirus shell to deliver large pieces of DNA into the cultured insect cells, instructing them to assemble the proteins we were interested in.” When the scientists realised that the same property could potentially transform gene therapy in human cells, they created this new DNA repair kit.
Dr Aulicino added: “There are many avenues to utilise our system. In addition to podocin repair, we could show that we can simultaneously correct many errors in very different places in the genome efficiently, by using our single baculovirus delivery system and the most recent editing techniques available.”
During hot weather events, people taking beta blockers and antiplatelet medications such as aspirin could be at increased risk of a myocardial infarction (MI), amplifying the risk already present from hot weather.
A new study published in Nature Cardiovascular Research found that, among people suffering non-fatal MI associated with hot weather, a greater portion are taking these heart drugs.
“Patients taking these two medications have higher risk,” said Assistant Professor Kai Chen, first author of the study. “During heat waves, they should really take precautions.”
External environmental factors like air pollution and cold weather can trigger MIs, and there is growing evidence to suggest that hot weather can do so, too. But epidemiologists are still working to identify which groups of people are most vulnerable to these environmental extremes.
The authors looked at 2494 cases sourced from a registry, in which individuals experienced a non-fatal MI in Augsburg, Germany during the hot-weather months (May–September) between 2001 and 2014.
In previous research, they had shown that exposure to either heat or cold made heart attacks more likely, and they calculated that heat-related MI rates would rise once the planet has warmed by 2–3°C.
The current study built on that research by examining patients’ medication use prior to their MI.
They analysed the data in a way that let patients serve as their own controls, by comparing heat exposure on the day of the MI versus the same days of the week within the same month. That is, if a person had an NI on the third Thursday in June, the authors compared their temperature exposure that day to their temperature exposure on other, “control” Thursdays in June.
It turned out that users of beta-blockers or antiplatelet medications were likelier to have an MI during the hottest days compared to control days. Antiplatelet medication use was associated with a 63% increase in risk and beta-blockers with a 65% increase. People taking both drugs had a 75% higher risk. Non-users of those medications were not more likely to have a heart attack on hot days.
When researchers compared younger patients (25–59 years) to older ones (60–74 years), they found, as expected, that the younger ones were a healthier group, with lower rates of coronary heart disease. Yet younger patients taking beta-blockers and antiplatelet medications were more susceptible to heat-related heart attack than older patients, despite the older ones having more heart disease.
Another clue that these two medication types may render people more vulnerable is that, other heart medications generally didn’t show a connection to heat-related heart attacks. An exception was statins, which taken by younger people, were associated with an over threefold risk of a heart attack on hot days.
“We hypothesise that some of the medications may make it hard to regulate body temperature,” Asst Prof Chen said. He plans to find out why in future studies.
The results suggest that as climate change progresses, heart attacks might become a greater hazard to some people with cardiovascular disease.
