Day: June 30, 2022

Norovirus and Other Enteric Viruses can Spread via Saliva

A microscopic view of salivary gland acinar epithelial cells (pink) infected with rotavirus (green), a type of enteric virus, in a mouse. Credit: Nihal Altan-Bonnet (NIH/NHLBI)

Enteric viruses can grow in the salivary glands of mice and spread through their saliva, scientists at the National Institutes of Health have discovered. Enteric viruses transmission through saliva suggests that coughing, talking, sneezing, sharing food and utensils, and even kissing all have the potential for spreading the viruses.

The findings, which appear in the journal Nature, could lead to better ways to prevent, diagnose, and treat diseases caused by these viruses, potentially saving lives.

Enteric viruses, such as noroviruses and rotaviruses, have long been known to spread by eating food or drinking liquids contaminated with faecal matter containing these viruses. Enteric viruses were thought to bypass the salivary gland and target the intestines, exiting later through faeces. Though another route of transmission was suspected, this theory remained largely untested until now.

Now researchers will need to confirm that salivary transmission of enteric viruses is possible in humans. If they find that it is, the researchers said, they may also discover that this route of transmission is even more common than the conventional route. A finding such as that could help explain, they said, why the high number of enteric virus infections each year worldwide fails to adequately account for faecal contamination as the sole transmission route.

“This is completely new territory because these viruses were thought to only grow in the intestines,” said senior author Nihal Altan-Bonnet, PhD. “Salivary transmission of enteric viruses is another layer of transmission we didn’t know about. It is an entirely new way of thinking about how these viruses can transmit, how they can be diagnosed, and, most importantly, how their spread might be mitigated.”

Dr Altan-Bonnet, who has studied enteric viruses for years, said the discovery was completely serendipitous. Her team had been conducting experiments with enteric viruses in infant mice, which are the animal models of choice for studying these infections because their immature digestive and immune systems make them susceptible to infections.

For the current study, the researchers fed a group of newborn mice that were less than 10 days old with either norovirus or rotavirus. The mouse pups were then returned to cages and allowed to suckle their mothers, who were initially virus-free. After just a day, one of Dr Altan-Bonnet’s team members, NHLBI researcher and study co-author Sourish Ghosh, PhD, noticed something unusual. The mouse pups showed a surge in IgA antibodies – important disease-fighting components – in their guts. This was surprising considering that the immune systems of the mouse pups were immature and not expected to make their own antibodies at this stage.

Ghosh also noticed other unusual things: The viruses were replicating in the mothers’ milk duct cells at high levels. When Dr Ghosh collected milk from the breasts of the mouse mothers, he found that the timing and levels of the IgA surge in the mothers’ milk mirrored the timing and levels of the IgA surge in the guts of their pups. It seemed the infection in the mothers’ breasts had boosted the production of virus-fighting IgA antibodies in their breast milk, which ultimately helped clear the infection in their pups, the researchers said.

Eager to know how the viruses got into the mothers’ breast tissue in the first place, the researchers conducted additional experiments and found that the mouse pups had not transmitted the viruses to their mothers through the conventional route – by leaving contaminated faeces in a shared living space for their mothers to ingest. That’s when the researchers decided to see whether the viruses in the mothers’ breast tissue might have come from the saliva of the infected pups and somehow spread during breastfeeding.

To test the theory, Dr Ghosh collected saliva samples and salivary glands from the mouse pups and found that the salivary glands were replicating these viruses at very high levels and shedding the viruses into the saliva in large amounts. Additional experiments quickly confirmed the salivary theory: suckling had caused both mother-to-pup and pup-to-mother viral transmission.

Source: National Institutes of Health

Sleep Now Part of American Heart Association’s Cardiovascular Health Score

Sleeping man
Photo by Mert Kahveci on Unsplash

Sleep duration is now considered an essential component for ideal heart and brain health. Life’s Essential 8™ cardiovascular health score replaces Life’s Simple 7™, according to a new American Heart Association advisory published in Circulation.

Other updates to the measures of optimal cardiovascular health, now for anyone ages 2 and older, include a new guide to assess diet; accounting for exposure to second-hand smoke and vaping; using non-HDL cholesterol instead of total cholesterol to measure blood lipids; and expanding the blood sugar measure to include haemoglobin A1c to assess Type 2 diabetes risk.

“The new metric of sleep duration reflects the latest research findings: sleep impacts overall health, and people who have healthier sleep patterns manage health factors such as weight, blood pressure or risk for Type 2 diabetes more effectively,” said American Heart Association President Professor Donald M. Lloyd-Jones, MD, who led the advisory writing group. “In addition, advances in ways to measure sleep, such as with wearable devices, now offer people the ability to reliably and routinely monitor their sleep habits at home.”

The Association first defined the seven metrics for cardiovascular health in 2010 to identify the specific health behaviours and health factors that drive optimal heart and brain health.

After 12 years and more than 2400 scientific papers on the topic, new discoveries in heart and brain health and in the ways to measure cardiovascular health provided an opportunity to revisit each health component in more detail. Four of the original metrics have been redefined for consistency with newer clinical guidelines or compatibility with new measurement tools. Also, the scoring system can now be applied to anyone ages 2 and older.

The Life’s Essential 8™ components of optimal cardiovascular health are divided into two major areas: health behaviours (diet, physical activity, nicotine exposure and sleep) and health factors (BMI, cholesterol levels, blood sugar and blood pressure). “The idea of optimal cardiovascular health is important because it gives people positive goals to work toward at any stage of life,” said Lloyd-Jones.

“Life’s Simple 7™ has served as a proven, powerful tool for understanding how to achieve healthy aging and ways to improve cardiovascular health while decreasing the risks of developing heart disease and stroke, as well as cancer, dementia and many other chronic diseases,” he said. “Given the evolving research, it was important to address some limitations to the original metrics, particularly in ways they’ve been applied to people from diverse racial and ethnic populations.”

Prof Lloyd-Jones explained that some of the previous metrics, such as diet, were not as sensitive to differences among people, or as responsive to changes over time within a single individual. “We felt it was the right time to conduct a comprehensive review of the latest research to refine the existing metrics and consider any new metrics that add value to assessing cardiovascular health for all people.”

Life’s Essential 8™ includes:

  1. Diet (updated):  A new guide to assess diet quality for adults and children at the individual level (for individual health care and dietary counselling) and at the population level (for research and public health purposes).
  2. Physical activity (no changes): The optimal level is 150 minutes of moderate physical activity or more per week or 75 minutes per week of vigorous-intensity physical activity for adults; 420 minutes or more per week for children ages 6 and older; and age-specific modifications for younger children.
  3. Nicotine exposure (updated): Use of inhaled nicotine-delivery systems, which includes e-cigarettes or vaping devices, is added since the previous metric only monitored traditional, combustible cigarettes. This reflects use by adults and youth and their implications on long-term health. Life’s Essential 8™ also includes second-hand smoke exposure for children and adults.
  4. Sleep duration (new): Sleep duration is associated with cardiovascular health. Measured by average hours of sleep per night, the ideal level is 7-9 hours daily for adults. Ideal daily sleep ranges for children are 10-16 hours per 24 hours for ages 5 and younger; 9-12 hours for ages 6-12 years; and 8-10 hours for ages 13-18 years.
  5. Body mass index (no changes): The writing group acknowledges that body mass index (BMI) is an imperfect metric, yet it is easily calculated and widely available; therefore, BMI continues as a reasonable gauge to assess weight categories that may lead to health problems. BMI of 18.5–24.9 is associated with the highest levels of cardiovascular health. The writing group notes that BMI ranges and the subsequent health risks associated with them may differ among people from diverse racial or ethnic backgrounds or ancestry. This aligns with the World Health Organization’s recommendations to adjust BMI ranges for people of Asian or Pacific Islander ancestry because recent evidence indicates their risk of conditions such as  CVD or Type 2 diabetes is higher at a lower BMI.
  6. Blood lipids (updated): The metric for blood lipids (cholesterol and triglycerides) is updated to use non-HDL cholesterol as the preferred number to monitor, rather than total cholesterol. Other forms of cholesterol, when high, are linked to CVD risk. This shift is made because non-HDL cholesterol can be measured without fasting beforehand (thereby increasing its availability at any time of day and implementation at more appointments) and reliably calculated among all people.
  7. Blood glucose (updated): This metric is expanded to include the option of haemoglobin A1c readings or blood glucose levels for people with or without Type 1 or Type 2 diabetes or prediabetes. Haemoglobin A1c can better reflect long-term glycaemic control.
  8. Blood pressure (no changes): Blood pressure criteria remain unchanged from the Association’s 2017 guidelines that established levels less than 120/80 mm Hg as optimal, and hypertension defined as 130-139 mm Hg systolic pressure (the top number in a reading) or 80-89 mm Hg diastolic pressure (bottom number).

Each component of Life’s Essential 8™, which is assessed by the My Life Check tool, has an updated scoring system ranging from 0 to 100 points. The overall cardiovascular health score from 0 to 100 points is the average of the scores for each of the 8 health measures. Overall scores below 50 indicate “poor” cardiovascular health, and 50-79 is considered “moderate” cardiovascular health. Scores of 80 and above indicate “high” cardiovascular health. The advisory recommends measuring cholesterol, blood sugar, blood pressure, height and weight at least every five years for the most complete and accurate Life’s Essential 8™ score.

The writing group also reviewed data about the impacts of stress, mental health and social determinants of health, such as access to health care, income or education level, and structural racism, which are critical to understanding the foundations of health, particularly among people from diverse racial and ethnic populations.

“We considered social determinants of health carefully in our update and determined more research is needed on these components to establish their measurement and inclusion in the future,” said Lloyd-Jones. “Nonetheless, social and structural determinants, as well as psychological health and well-being, are critical, foundational factors in an individual’s or a community’s opportunity to preserve and improve cardiovascular health. We must consider and address all of these issues for people to have the opportunity for a full, healthy life as measured by Life’s Essential 8™.”

Source: American Heart Association

Greater Hospitalisation or ED Visit Risk for Cannabis Users

Photo by RODNAE Productions from Pexels

Compared to non-users, cannabis users have 22% higher rates in emergency department (ED) visits and hospitalisations, according to new research findings. The study, published in BMJ Open Respiratory Research revealed that serious physical injury and respiratory-reasons were the two leading causes of ED visits and hospitalisations among cannabis users.

The findings suggest an association between cannabis use and negative health events, which the researchers say should underline the need to educate and remind the public of the harmful impacts of cannabis on health.

“Our research demonstrates that cannabis use in the general population is associated with heightened risk of clinically serious negative outcomes, specifically, needing to present to the ED or be admitted to hospital,” said Dr Nicholas Vozoris, lead author, a respirologist at St. Michael’s and an associate scientist at the hospital’s Li Ka Shing Knowledge Institute.

“Unlike tobacco, there is some uncertainty or controversy regarding the adverse health impacts of cannabis. Some individuals may perceive that cannabis has some health benefits and is otherwise benign. Our research highlights to those using – or considering to use – cannabis, that this behaviour is associated with important negative health events.”

To compare health outcomes among cannabis users and individuals who don’t use cannabis, researchers used data collected in a survey of individuals who self-reported cannabis use and linked it with health administrative data for Ontario residents.

Using propensity score matching, researchers compared the health outcomes of nearly 4800 individuals who reported any cannabis use in the preceding 12 months with the health outcomes of over 10 000 individuals never-users, or having used cannabis only once and more than 12 months ago. Researchers incorporated 31 different variables while matching study participants to minimise an unfair comparison, including demographics, multiple physical and mental health diseases, and tobacco, alcohol and illicit drug use.

The study’s main aim was to see if there was a link between cannabis use and respiratory-related hospitalisation or ED visits. No significant associations were found between cannabis use and respiratory-related ED visits, hospitalisations, or death from any cause. However, they did find that overall visits to the ED or hospitalisations for any reason was significantly higher among cannabis users.

In addition to having greater odds of ED visits or hospitalisation, the findings show that one of every 25 cannabis users will go to the emergency department (ED) or be admitted to hospital within a year of using cannabis.

Among the reasons for ED visits or hospitalisations of cannabis users, acute trauma was the most common, with 15% of cannabis users who got medical attention receiving it for this reason, and 14% receiving care for respiratory reasons.

“The results of our research support that health care professionals and government should discourage recreational cannabis consumption in the general population,” noted Dr Vozoris.

Source: EurekAlert!

Omicron Viral Load Shedding May Be Unaffected by Vaccination

SARS-CoV-2 virus
SARS-CoV-2 virus. Source: Fusion Medical Animation on Unsplash

A small study published in the New England Journal of Medicine has found that viral load shedding of the omicron variant is similar to other strains, and is not significantly affected by vaccination status.

The SARS-CoV-2 omicron variant has a shorter incubation period and a higher transmission rate than previous variants. Recently, the Centers for Disease Control and Prevention recommended shortening the strict isolation period for infected persons from 10 days to 5 days after symptom onset or initial positive test, followed by 5 days of masking. However, the viral delay kinetics and load shedding of omicron is still unclear.

Using nasal swabs to measure viral load, sequencing, and viral culture, they enrolled 66 participants, including 32 with delta variant and 34 with omicron. Participants who received COVID–specific therapies were excluded; only one participant was asymptomatic.

The characteristics of the participants were similar in the two variant groups except that more participants with omicron infection had received a booster vaccine than had those with delta infection (35% vs 3%). After adjustments for age, sex, and vaccination status, the number of days from an initial positive polymerase-chain-reaction (PCR) assay to a negative PCR assay and the number of days from an initial positive PCR assay to culture conversion were similar in the two variant groups.

The median time from the initial positive PCR assay to culture conversion was 4 days in the delta group and 5 days in the omicron group; the median time from symptom onset or the initial positive PCR assay, whichever was earlier, to culture conversion was 6 days and 8 days, respectively. There were no appreciable between-group differences in the time to PCR conversion or culture conversion according to vaccination status, although the sample size was quite small, which led to imprecision in the estimates.

In these participants with nonsevere COVID, the viral decay kinetics were similar with omicron infection and delta infection. No large differences in the median duration of viral shedding was seen among participants who were unvaccinated, vaccinated but not boosted, and those who were vaccinated and boosted.

Discussing limitations, the authors cautioned that the small sample size limits precision, and there are possible residual confounding variables. Further studies are need to properly correlate culture positivity with infectivity.

They conclude by saying: “Our data suggest that some persons who are infected with the omicron and delta SARS-CoV-2 variants shed culturable virus more than 5 days after symptom onset or an initial positive test.”

Could Carbon Monoxide Treat Inflammation?

Photo by Samuel Ramos on Unsplash

While carbon monoxide is associated with asphyxiation cases, in small doses it also has beneficial qualities, helping reduce inflammation and stimulate tissue regeneration.

But now, a team of researchers have devised a novel way to deliver carbon monoxide to the body without its hazardous effects. Inspired by techniques used in molecular gastronomy, they were able to incorporate carbon monoxide into stable foams that can be delivered to the digestive tract.

In a mouse study, the researchers showed that these foams reduced inflammation of the colon and helped to reverse acute liver failure caused by acetaminophen overdose. The researchers said that their new technique, described today in a Science Translational Medicine paper, could also be used to deliver other therapeutic gases.

“The ability to deliver a gas opens up whole new opportunities of how we think of therapeutics. We generally don’t think of a gas as a therapeutic that you would take orally (or that could be administered rectally), so this offers an exciting new way to think about how we can help patients,” said Giovanni Traverso, a professor at MIT and a gastroenterologist at Brigham and Women’s Hospital.

Inspired by fine cuisine

Since the late 1990s, Leo Otterbein, a professor of surgery at Harvard Medical School and Beth Israel Deaconess Medical Center, has been studying the therapeutic effects of low CO doses. The gas has been shown to impart beneficial effects in preventing rejection of transplanted organs, reducing tumour growth, and modulating inflammation and acute tissue injury. 

When inhaled at high concentrations, CO binds to haemoglobin in the blood and prevents the body from obtaining enough oxygen, which can be fatal in same cases. However, at lower doses, it has beneficial effects such as reducing inflammation and promoting tissue regeneration, Prof Otterbein said.

“We’ve known for years that carbon monoxide can impart beneficial effects in all sorts of disease pathologies, when given as an inhaled gas,” he saud. “However, it’s been a challenge to use it in the clinic, for a number of reasons related to safe and reproducible administration, and health care workers’ concerns, which has led to people wanting to find other ways to administer it.”

Prof Traverso’s lab specialises in developing novel methods for delivering drugs to the gastrointestinal tract. They came up with the idea of incorporating the gas into a foam, much the way that chefs use carbon dioxide to create foams infused with fruits, vegetables, or other flavours.

Culinary foams are usually created by adding a thickening or gelling agent to a liquid or a solid that has been pureed, and then either whipping it to incorporate air or using a specialised siphon that injects gases such as carbon dioxide or compressed air.

The MIT team created a modified siphon that could be attached to any kind of gas canister, allowing them to incorporate CO into their foam. To create the foams, they used food additives such as alginate, methyl cellulose, and maltodextrin. Xantham gum was also added to stabilise the foams. By varying the amount of xantham gum, the researchers could control the release rate of CO gas from the foam.

After showing that they could control the timing of the gas release in the body, the researchers decided to test the foams for a few different applications. First, they studied two types of topical applications, analogous to applying a cream to soothe itchy or inflamed areas. In a study of mice, they found that delivering the foam rectally reduced inflammation caused by colitis or radiation-induced proctitis (inflammation of the rectum that can be caused by radiation treatment for cervical or prostate cancer).

Current treatments for colitis and other inflammatory conditions such as Crohn’s disease usually involve drugs that suppress the immune system, which can make patients more susceptible to infections. Treating those conditions with a foam that can be applied directly to inflamed tissue offers a potential alternative, or complementary approach, to those immunosuppressive treatments, the researchers said. While the foams were given rectally in this study, it could also be possible to deliver them orally, the researchers say.

Controlling the dose

The researchers then investigated possible systemic applications to deliver CO to remote organs, such as the liver, because of its ability to diffuse from the GI tract elsewhere in the body. For this study, they used a mouse model of acetaminophen overdose, which causes severe liver damage. They found that gas delivered to the lower GI tract was able to reach the liver and greatly reduce the amount of inflammation and tissue damage seen there.

In these experiments, the researchers did not find any adverse effects after the carbon monoxide administration. A healthy individual has CO levels of ~1% in the bloodstream, and studies of human volunteers have shown that levels as high as 14% can be tolerated without adverse effects.

“We think that with the foam used in this study, we’re not even coming close to the levels that we would be concerned about,” Otterbein says. “What we have learned from the inhaled gas trials has paved a path to say it’s safe, as long as you know and can control how much you’re giving, much like any medication. That’s another nice aspect of this approach — we can control the exact dose.”

In this study, the researchers also created carbon-monoxide containing gels, as well as gas-filled solids, using techniques similar to those used to make Pop Rocks, the hard candies that contain pressurised carbon dioxide bubbles. They plan to test those in further studies, in addition to developing the foams for possible tests in human patients.

Source: MIT