How plants produce defensive toxins without harming themselves

Defense and autotoxicity: Researchers elucidate the biosynthesis and mode of action of diterpene glycosides in wild tobacco

MAX PLANCK INSTITUTE FOR CHEMICAL ECOLOGY

Research News

 

IMAGE: THE LARVA OF A TOBACCO HAWKMOTH MANDUCA SEXTA ON A WILD TOBACCO LEAF: A DETAILED CHEMICAL ANALYSIS OF LARVAL FRASS (SMALL BLACK BALL) REVEALED HOW TOXINS ARE ACTIVATED IN THE... view more 

CREDIT: ANNA SCHROLL

Plants produce toxic substances to defend themselves against herbivores. In a new study, scientists from the Max Planck Institute for Chemical Ecology in Jena and the University of Münster, Germany, were able to describe in detail the biosynthesis and exact mode of action of an important group of defensive substances, the diterpene glycosides, in wild tobacco plants. Diterpene glycosides allow plants to fend off herbivores. The study shows that these plant chemicals attack certain parts of the cell membrane. To protect themselves from their own toxins and to prevent their cell membranes from being damaged, tobacco plants store these substances in a non-toxic form, which is synthesized in a very particular way. Autotoxicity and the protection against it seem to play a greater role in the evolution of plant defenses than previously thought (Science, doi: 10.1126/science.abe4713, January 2021).

Many plants produce chemical defenses to protect themselves against being eaten. Still little is known about what makes these substances toxic to their consumers. Researchers at the Max Planck Institute for Chemical Ecology and the University of Münster have now investigated how plants produce toxins and store them in their tissues without harming themselves. In particular, they wanted to know whether the mechanisms of autotoxicity and its prevention share similar mechanisms as the toxic characteristics that provide defense against herbivores.

Autotoxicity and defense

For their experiments, they chose diterpene glycosides from Nicotiana attenuata plants, a wild tobacco species. "These substances occur at very high concentrations in the leaves of tobacco plants. But we had no idea why they were such effective defenses or why they could be so toxic to produce. So the situation was completely different from the other very abundant toxin that this plant produces, namely, nicotine. Nicotine is a specific neurotoxin. Since plants lack nerves and muscles, they offer no target for the toxin. So producing and storing nicotine does not harm plants," says Ian Baldwin from the Department of Molecular Ecology at the Jena Max Planck Institute, where the study was carried out.

To their surprise, the researchers found that tobacco plants which had been transformed so they could no longer produced two proteins involved in the biosynthesis of the diterpene glycosides and thus also not form the defensive substances otherwise stored in the leaves in large amounts, showed conspicuous symptoms of self-poisoning: they were sick, unable to grow normally, and could no longer reproduce. Further experiments revealed that certain components of the cell membrane, so-called sphingolipids, had been attacked.

Targeting the cell membrane

Sphingolipids are substances found in all animals and plants, including the enemies of wild tobacco, the larvae of the tobacco hawkmoth Manduca sexta. The researchers therefore asked whether the sphingolipid metabolism could be the target of the diterpene glycosides. In fact, Manduca sexta caterpillars, which had fed on plants without diterpene glycosides, grew significantly better than larvae, which had fed on controls that contained the defensive chemicals. Analyses of the frass of Manduca sexta larvae, which had ingested diterpene glycosides with their food, provided further insights, as the degradation of the plant toxins during larval digestion is more or less in reverse order to the synthesis of the substances in the plant. Plants prevent self-harm by storing the defensive substances in a non-toxic form. However, when insects feed on the plant, a part of the non-toxic molecule is cleaved off and the chemical becomes activated or "armed". "Interestingly, in both cases, in plants with incomplete diterpene glycoside biosynthesis and in feeding caterpillars, the target of the toxins is the sphingolipid metabolism," says first author Jiancai Li.

Sphingolipids are mediators in many physiological processes. This makes the effect of diterpene glycosides on sphingolipid metabolism so intriguing. "Diterpene glycosides and their derivatives can have broad defensive functions against many agricultural pests and pathogenic fungi. At the same time, many human diseases, such as diabetes, cancers and some neurodegenerative diseases are also associated with elevated sphingolipid metabolisms," says Shuqing Xu from the Institute for Evolution and Biodiversity at the University of Münster, who is one of the senior authors of the study. Physicians have been searching for effective substances to treat these diseases by inhibiting the sphingolipid metabolism. The diterpene glycosides studied here could be potential candidates for further investigations.

"Frassomics" - a new powerful tool to study interactions between organisms

The analysis of larval frass proved to be the key to success in this study. The scientists call this new approach "frassomics": a combination of frass (larval droppings) and metabolomics - the analysis of all metabolites in an organism. "From this work, we realized that frassomics can be a very powerful research tool. The analysis of larval frass can provide metabolic clues about how what one organism produces is metabolized by consumer organisms," says Ian Baldwin.

The scientists plan to gain more insights into the "digestive duets" that occur between plants and insects, in order to better understand ecological interactions between plants, insects and microorganisms.

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Original Publication: Li, J., Halitschke, R., Li, D., Paetz, C., Su, H., Heiling, S., Xu, S., Baldwin, I. T. (2021). Controlled hydroxylations of diterpenoids allow for plant chemical defense without autotoxicity, Science, DOI: 10.1126/science.abe4713 https://doi.org/10.1126/science.abe4713

Further Information:

Prof. Dr. Ian T. Baldwin, Tel. +49 3641 57 1100, E-Mail: baldwin@ice.mpg.de, Max Planck Institute for Chemical Ecology, Hans-Knöll-Straße 8, 07745 Jena, Germany

Prof. Dr. Shuqing Xu, Tel. +49 251 83 21090, E-Mail: shuqing.xu@uni-muenster.de, Institute for Evolution & Biodiversity, University of Münster, Hüfferstraße 1, 48143 Münster, Germany

Contact and Picture Requests:

Angela Overmeyer M.A., Max Planck Institute for Chemical Ecology, Hans-Knöll-Str. 8, 07743 Jena, Germany, Tel. +49 3641 57-2110, E-Mail overmeyer@ice.mpg.de

Download of videos and high-resolution images via http://www.ice.mpg.de/ext/downloads2021.html

Researchers show Irish soil can offer more hope in fight against antibiotic resistance

Scientists make exciting discovery in the quest to discover new antibiotics.

SWANSEA UNIVERSITY

Research News

 

IMAGE: RESEARCHERS HAVE DISCOVERED SOIL IN THE WEST FERMANAGH SCARPLANDS CONTAINS SEVERAL SPECIES OF THESE ANTIBIOTIC PRODUCING ORGANISMS. view more 

CREDIT: TRADITIONAL MEDICINE GROUP

Scientists who highlighted the bug-busting properties of bacteria in Northern Irish soil have made another exciting discovery in the quest to discover new antibiotics.

The Traditional Medicine Group, an international collaboration of scientists from Swansea University, Brazil and Northern Ireland, have discovered more antibiotic-producing species and believe they may even have identified new varieties of antibiotics with potentially life-saving consequences.

Antibiotic resistant superbugs could kill up to 1.3 million people in Europe by 2050 - the World Health Organisation (WHO) describes the problem as "one of the biggest threats to global health, food security, and development today".

The search for replacement antibiotics to combat multi-resistance has prompted researchers to explore new sources, including folk medicines focusing on environments where well-known antibiotic producers like Streptomyces can be found.

The Traditional Medicine Group discovered that soil used in ancient Irish folk medicine in the West Fermanagh scarplands contains several species of these antibiotic producing organisms. This area of caves, alkaline grassland and bog is scattered with many remnants of previous Neolithic habitation.

One of the research team, Dr Gerry Quinn, a previous resident of Boho, County Fermanagh, has been aware of the healing traditions of the area for many years. Several years ago, an analysis of the soil there led to the team discovering a previously unknown strain of bacteria effective against four of the top six hospital superbugs that are resistant to antibiotics, including MRSA.

Since then, their research has continued but given local religious sensitivities and the self-limiting nature of the original site, the group relocated their search to another area of the West Fermanagh scarplands that retained the essential alkaline nature of the grasslands whilst also providing a link to traditional folk medicine.

Dr Paul Facey, one of the lead researchers from Swansea University said: "The fact that traditional medicine is incorporated in many local folk tales led us to believe that there was a good possibility of finding strong antibiotic producing organisms in other locations in these limestone hills."

The group discovered that their latest finding was able to express an even wider range of antimicrobial activity than their previous discovery.

The results of this study have now been published in MDPI Applied Microbiology and the DNA sequence has been deposited in the American national collection.

Antibiotic tests performed by Dr Quinn, Simms Adu, from Ulster University, and Swansea University's Nada Alharbi reveal that Streptomyces sp. CJ13 inhibits the growth of multi-resistant organisms such as:

• Gram negative Pseudomonas aeruginosa, a common opportunistic pathogen associated with chronic lung infections in cystic fibrosis patients;
• MRSA, a common opportunistic pathogen often resistant to many antibiotics;
• Anaerobic bacteria, usually found in deep wounds, which cause serious infections; and
• Candida, a yeast species often overlooked in mixed bacterial infections.

The group has yet to chemically identify the compounds responsible for antibiotic activity but preliminary analysis indicates there are genetic similarities to other known antibiotic production genes.

Even though the antibiotic genes found in Streptomyces sp. CJ13 are not identical to template antimicrobials, it raises the interesting possibility that these could be new varieties of antibiotics.

Given the significant contributions made by Streptomyces to the fields of cancer and anti-viral therapies, team member Hamid Bakshi added: "We are confident in the great potential of our most recent discovery to provide many interesting discoveries."

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Rare lichen unique to Florida discovered in museum collections, may be extinct

FLORIDA MUSEUM OF NATURAL HISTORY

Research News

 

IMAGE: THE ONLY RECORDS OF THE NEWLY-IDENTIFIED LICHEN CORA TIMUCUA ARE 32 SPECIMENS IN MUSEUM COLLECTIONS COLLECTED IN FLORIDA BETWEEN 1885 AND 1985. UP TO 90% OF ITS NATIVE PINE SCRUB... view more 

CREDIT: ROBERT LÜCKING

GAINESVILLE, Fla. --- Scientists have found a new species of fleshy verdigris lichen, thanks to DNA analysis of museum specimens. Misidentified by its original collectors, the lichen is only known from 32 specimens collected in North and Central Florida scrubland between 1885 and 1985. Now the hunt is on to find it in the wild - if it still exists.

The lichen, named Cora timucua in honor of Florida's Timucua people, is critically endangered, even more so than the federally protected Florida perforate reindeer lichen, and possibly extinct. Researchers are holding out hope that C. timucua may persist in undisturbed pockets of the state's dwindling pine scrub habitat, though recent searches came up empty.

"The million-dollar question is 'Where is this lichen?'" said Laurel Kaminsky, a digitization manager at the Florida Museum of Natural History and co-author of the study. "The optimist in me says it's still out there."

Kaminsky said the sparse information recorded by the lichen's collectors makes it difficult to retrace their steps. More widespread in the early 20th century, C. timucua was collected only from the Ocala National Forest and O'Leno State Park after 1968, two of Florida's last remaining scrub ecosystems. Citrus groves and urban developments have replaced up to 90% of the state's sand pine scrub.

"If it's anywhere, it's going to take a lot of looking in very specific habitats to find it," Kaminsky said.

Affectionately dubbed "Timucua heart lichen," the new species resembles a shelf fungus and is about the size of a sand dollar with scalloped edges. It can be distinguished from wood-rotting fungi by its texture: felty and papery, with curved lobes and a cracked underside.

But its color is an enigma. The lichen is light gray when dry, but specimens turn a deep blue-green and bleed a reddish-brown pigment when wet in a laboratory setting. Without photos and detailed descriptions of the lichen in nature, scientists don't yet know how it reacts to moisture in the wild.

"In general, people take nature for granted, and the Timucua heart lichen story might tell us sometimes we are too late," said Manuela Dal Forno, senior author of the study and a lichenologist at the Botanical Research Institute of Texas. "Right now, we need everybody's help in trying to locate this lichen in Florida."

Kaminsky said Timucua heart lichen likely prefers old-growth pine scrub habitat, which has taller trees and established populations of native Florida plants, such as rusty lyonia, a shrub characterized by reddish fibers lining its leaves. But hikers should avoid collecting any potential specimens they find: Instead, they can photograph the lichen and upload images to the Timucua Heart Lichen Project on the community science platform iNaturalist for identification.

Florida's hidden lichen life

Lichens are partnerships between fungi and photosynthesizing organisms and play a key role in their ecosystems by enriching soils and cycling nutrients. But much of the world's lichen diversity remains hidden. A chronic shortage of lichen experts led to the delay in Timucua heart lichen's discovery, Kaminsky said. She added that Florida could harbor as many as 1,000 lichen species, many of which remain undescribed and whose populations could also be imperiled.

A previous survey of South Florida's Fackahatchee Strand Preserve led by Robert Lücking, a curator at Berlin's Botanical Garden and Botanical Museum and lead author of the C. timucua study, found more than 400 lichen species in about 250 acres. Of the 400 species, 18 were new to science and 100 had yet to be recorded in North America.

"This emphasizes how little we know about lichen diversity and their genetic information, as well as the importance of digitization projects," said Dal Forno, also a research associate at the Smithsonian's National Museum of Natural History. "There are so many lichens out there, but not enough lichenologists to study them."

Timucua heart lichen belongs to the genus Cora, a group of nearly 200 tropical lichens - once thought to be a single species - typically found in mountain habitats. Its discovery in Florida is the northernmost record of a Cora species, and the new species is the sole representative of its genus in the U.S.

Even if the species is extinct, studying its DNA could help scientists understand how the species arrived in Florida. Timucua heart lichen's closest known relatives are in Colombia and Brazil, raising questions about how C. timucua was able to grow in a habitat so different from its sister species, Dal Forno said.

Digital museum specimens led to discovery

Increasingly, researchers need not pack a tent and head into the field to find new species. Instead, they can search online databases of specimen data from museums around the world. In 2012, a National Science Foundation grant helped scientists digitize lichens from the Florida Museum's fungal herbarium, uploading basic specimen information and images to two international data networks, the Global Biodiversity Information Facility and the Consortium of North American Lichen Herbaria.

It was on the web that Lücking and Gary Perlmutter, acting curator of lichens at the University of North Carolina at Chapel Hill herbarium and a study co-author, spotted clusters of Florida Cora specimens, far outside the genus's known range. They contacted Kaminsky, suspecting DNA analysis would uncover misidentified specimens.

"I knew we had these specimens, but I just thought everybody else knew," Kaminsky said. "The digitization just opened it up for other people to find it and do cool things with it."

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James Lawrey of George Mason University also co-authored the study.

Bees respond to wildfire aftermath by producing more female offspring

OREGON STATE UNIVERSITY

Research News

 

IMAGE: BLUE ORCHARD BEE view more 

CREDIT: JIM RIVERS, OSU COLLEGE OF FORESTRY

CORVALLIS, Ore. - Researchers at Oregon State University have found that the blue orchard bee, an important native pollinator, produces female offspring at higher rates in the aftermath of wildfire in forests.

The more severe the fire had been, the greater percentage of females - more than 10% greater in the most badly burned areas relative to areas that burned the least severely.

"This is one of the first studies that has looked at how forest fire severity influences bee demography," said Jim Rivers, an animal ecologist with the OSU College of Forestry. "Sex ratio varied under different fire conditions but the number of young produced did not, which indicates bees altered the sex of their offspring depending on the degree of fire severity."

Female bees control the sex of their offspring, laying eggs fertilized with sperm that become females, or non-fertilized eggs that become males.

Bees pollinate many of the flowering plants that make up native ecosystems and food chains Understanding how fire - expected to increase in frequency and severity - influences their reproductive outputs is an important part of knowing how post-fire management actions could help or harm bees.

"We placed bees on different sites within recently burned mixed-conifer forest in southwestern Oregon and used them as a measuring stick to tell us how good the bee habitat was," said Sara Galbraith, a postdoctoral researcher in the College of Forestry. "Adjusting offspring production toward the more expensive offspring sex shows a functional response to changes in habitat quality via an increased density of flowering plants."

In general, pollinators benefit from canopy-reducing fires in dense conifer forest ecosystems; flowering plant abundance usually increases for several years following a fire, resulting in food resources that enhance wild bee diversity and abundance.

Bees are the most important among the Earth's pollinators, which combine for an estimated $100 billion in global economic impact each year. Oregon is home to more than 600 species of native bees.

Animal pollinators enhance the reproduction of nearly 90% of the Earth's flowering plants, including many food crops.

Pollinators are an essential component of insect and plant biodiversity. Bees are the standard bearer because they're usually present in the greatest numbers and because they're the only pollinator group that feeds exclusively on nectar and pollen their entire life.

For this study involving the blue orchard bee, known scientifically as Osmia lignaria, Galbraith, Rivers and James Cane of the U.S. Department of Agriculture set up nest blocks containing a standardized number and sex ratio of pre-emergent adult bees.

They then looked at the relationship between fire severity and reproductive output, sex ratio and offspring mass at the local (within 100 meters of the blocks) and landscape (750 meters) scales. Female bees forage across both scales when caring for offspring.

"In fire-prone landscapes, there is variation in species-level response to wildfire that serves to maintain ecosystem structure and function," Rivers said. "With the blue orchard bee and similar species, foraging females invest in larger progeny and more females when more resources are available."

The findings showed that burned mixed-conifer forest provides forage for the blue orchard bee along a gradient of severity, and that the rise in floral resources that comes after high-severity fire causes females to reallocate resources to the larger and more costly sex - females - when nesting.

"Our study revealed more female progeny than is typically observed with blue orchard bees," Galbraith said. "The greater proportion of females in areas surrounded by a more severely burned landscape indicates an investment in more female offspring because of greater resource availability."

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Findings were published in Oecologia. The Bureau of Land Management and the OSU College of Forestry supported this research.

 

Honeybees reveal how our floral landscape has changed over the last 65 years

Honeybees have been helping researchers from the National Botanic Garden of Wales track how the UK's fields, hedgerows, wild spaces and gardens have changed since the 1950s.

NATIONAL BOTANIC GARDEN OF WALES

Research News

IMAGE: HONEYBEE ON WHITE CLOVER AT THE NATIONAL BOTANIC GARDEN OF WALES view more 

CREDIT: STEFFAN JOHN

Honeybee historians might seem like a flight of fancy but these tiny pollinators have been helping researchers from the National Botanic Garden of Wales track how the UK's fields, hedgerows, wild spaces and gardens have changed since the 1950s.Using cutting-edge DNA barcoding techniques, scientists at the Botanic Garden identified which plants modern-day honeybees visited most often by looking at the pollen grains trapped within honey.

They compared this to a 1952 survey of honey plants where a microscope had been used to painstakingly identify pollen grains in honey sent from hives across the country. The differences were clear. White clover had been the most important plant for honeybees but, with fewer pastures today and increased use of herbicides and inorganic fertiliser in farming, this has dropped to second place. Now the insects are visiting much more of:

• their modern-day favourite, bramble
• oilseed rape, a plant which has a sting in its tail
• the highly invasive Himalyan balsam

Also important were spring-flowering shrubs and trees,including hawthorn (Cratageus monogyna), apple (Malus species), Cotoneaster species, sycamore and maples (Acer species), cherries and plums (Prunus species), and towards the end of the season, heather (Calluna vulgaris).

Dr Natasha de Vere, Head of Conservation and Research at the National Botanic Garden of Wales, said: "The last 65 years have been a period of profound change within the UK landscape. Agricultural intensification after the Second World War led to a decline in species-rich grasslands and permanent pastures, while hedgerows and woodland were destroyed so that field sizes could increase, and new crops were grown. The distribution and abundance of the UK's wildflowers has changed, with some species declining whilst new plants have been introduced.

"Natural historians, scientists and government agencies have made detailed records over this time, but they are not the only witnesses to this changing world. Honeybees also travel through these landscapes, flying through fields and woodlands, over hedgerows and croplands, searching for nectar and pollen to return to their hives."

The new research:

In 2017, Dr Laura Jones repeated a 1952 survey, undertaken by A.S.C. Deans, as part of her PhD research with the National Botanic Garden of Wales and Bangor University. She analysed 441 samples of honey sent in from across the UK. This time, instead of using a microscope, the pollen was identified using plant DNA barcoding, work for which the Botanic Garden has an international reputation.

White clover - in 1952 the most important plant for honeybees was white clover (Trifolium repens). In the new research, white clover was still the second most important plant but there was a significant reduction in its presence within the honey. In 1952 it was found in 93% of honey samples and was a major honey plant in 74% of these, but by 2017 it was found in 62% of samples and was a major source in only 31% - a sign that our modern-day landscape has far less white clover.

The Countryside Survey for the UK shows that between 1978 and 2007 white clover decreased within the landscape by 13%. It used to be a dominant plant within permanent pastures and was also often included in grass leys as a source of protein for livestock. Agricultural intensification led to a reduction in the amount of permanent pastures and increased use of inorganic nitrogen fertiliser meant that clover was less likely to be sown in grass leys. Reseeding without clover made it easier to control docks and thistles with a broad-spectrum herbicide that killed off all of the plants that were not grasses. Where white clover was still included in leys, much more regular cutting for silage meant that it was unlikely to be allowed to flower.

Bramble - with the reduction of such an important nectar source, honeybees needed to find alternative supplies of nectar and pollen. The research suggests that honeybees increased the amount of bramble, Rubus fruticosus, in their diets. Bramble and white clover flower at similar times and bramble increased significantly as a major honeybee plant between 1952 and 2017. In 1952, Rubus was found in 58% of honey samples but was a major source in only 5% of these. In 2017, bramble was found in 73% of honey samples and was a major honey plant in 36% of these.

Oilseed rape - first grown in the late 1960s. By 1988, 279,030 ha of oilseed rape (Brassica napus) were in production and this increased to 332,000 ha in 2000. The bright yellow fields are now a common sight in spring. In 1952 the genus Brassica, to which oilseed rape belongs, was a major plant in only 2% of honey samples, by 2017 this had increased to 21%. The presence of Brassica pollen within the honey was found to be significantly greater from hives found within 2 km of oil seed rape crops. Honeybees make full use of the nectar and pollen from oilseed rape and single-origin oilseed rape honey is now widely available. It has a high glucose content that makes it granulate very rapidly into a set, white honey with a mild flavour. The rapid granulation can cause problems for the beekeeper as if it is not extracted rapidly from the combs it can set hard and be impossible to remove.

But there is a sting in the tale of this new resource, as oilseed rape seeds are often treated with neonicotinoid insecticides which harm honeybees. These neonic insecticides are currently banned within the UK and hopefully this ban will remain in place.

Himalayan balsam - honeybees in their search for nectar and pollen have also tracked the emergence of an invasive species. Himalayan balsam (Impatiens glandulifera) was first introduced into the UK in 1839. Its fast-growing stature (up to 3 m tall), orchid-like flowers in shades of white, pink and purple, and exploding seed pods, appealed to Victorian gardeners. Himalayan balsam soon made its escape from the garden walls, first spreading slowly, then increasing more rapidly from the 1940s to the 1960s, gradually establishing along waterways and field margins. In 1952 it was present within UK honey at low levels, occurring in 3% of samples with only 1% as a major plant.

Himalayan balsam now rampages along riversides and road verges. In 2017 it was found within 15% of samples and was a major source in 6%. However, this is an under estimation of its importance, since most of the honey samples were provided in July and August, whilst Himalayan balsam tends to be used by honeybees later in the year. Himalayan balsam is now an important late season plant for honeybees, providing an abundant nectar source at a time of year when there is little else available. It helps the bees build up their winter stores and is sometimes sold by beekeepers as a single-origin straw-coloured honey with a sweet, fragrant, floral taste. It is easy to tell when honeybees are foraging on Himalayan balsam as they return to the hive with a characteristic whitewash of pollen covering their bodies, leading them to be called 'ghost bees'.

Himalayan balsam is undoubtedly a good plant for honeybees but this is a controversial issue as it is a highly invasive species listed under Schedule 9 of the Wildlife and Countryside Act 1981, making it an offence to plant or cause this species to grow in the wild. Its vigorous growth means it competes with native plants for light, nutrients and space. It dies back in winter leaving riverbanks bare and open to erosion whilst its dead stems and leaves can block waterways. Even its popularity with pollinators can cause problems, as it can outcompete native wildflowers for their services, leading to reduced seed production in native plants.

Dr de Vere added: "Honeybees and wild pollinators need abundant and diverse sources of nectar and pollen within the landscape, to provide sufficient, high-quality food. By understanding which plants are the most important sources we can provide recommendations on which plants to grow so that honeybees and wild pollinators can thrive."

Recommendations from the research include:

Landscape level changes to provide more floral resources. The UK needs more flower-filled hedgerows with bramble margins and grasslands rich in wildflowers. The conservation of remaining species-rich meadows is a priority, but the area that these habitats cover is vanishingly small.

To make the biggest gains in nectar and pollen, changes are needed in the most prevalent habitat in the UK today - improved grassland. Wildflowers are squeezed out to create grasslands dominated by a small number of grass species, where there are very few flowers to sustain pollinators. But because of the scale of this habitat, small changes here could vastly increase nectar resource. For honeybees providing more white clover in improved grasslands would be best, for other pollinators different flowers are more important.

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Socioeconomic Disparities in Patient Use of Telehealth During the Coronavirus Disease 2019 Surge

Ilaaf Darrat, MD, MBA1; Samantha Tam, MD, MPH1; Marwan Boulis, MD1; et alAmy M. Williams, PhD1
Author Affiliations Article Information
JAMA Otolaryngol Head Neck Surg. Published online January 14, 2021.

 doi:10.1001/jamaoto1.2020.516

Key Points

Question What demographic and socioeconomic factors were associated with patient participation in telehealth during the coronavirus disease 2019 (COVID-19) pandemic surge?

Findings In a cohort study of 1162 patients at a large, urban tertiary care center in the Midwest, age, sex, median household income, insurance status, and marital status were associated with patient participation in telehealth during the COVID-19 pandemic surge.

Meaning Similar characteristics that are associated with inequitable access to in-person medical care are also associated with inequitable access to telehealth; a focus on vulnerable patient populations in a changing landscape is necessary to provide timely and essential medical care.

Abstract

Importance The coronavirus disease 2019 (COVID-19) pandemic required the rapid transition to telehealth with the aim of providing patients with medical access and supporting clinicians while abiding by the stay-at-home orders.

Objective To assess demographic and socioeconomic factors associated with patient participation in telehealth during the COVID-19 pandemic.

Design, Setting, and Participants This cohort study included all pediatric and adult patient encounters at the Department of Otolaryngology–Head & Neck Surgery in a tertiary care, academic, multisubspecialty, multisite practice located in an early hot spot for the COVID-19 pandemic from March 17 to May 1, 2020. Encounters included completed synchronous virtual, telephone, and in-person visits as well as visit no-shows.

Main Outcomes and Measures Patient demographic characteristics, insurance status, and 2010 Census block level data as a proxy for socioeconomic status were extracted. Univariate and multivariate logistic regression models were created for patient-level comparisons.

Results Of the 1162 patients (604 females [52.0%]; median age, 55 [range, 0-97] years) included, 990 completed visits; of these, 437 (44.1%) completed a virtual visit. After multivariate adjustment, females (odds ratio [OR], 1.71; 95% CI, 1.11-2.63) and patients with preferred provider organization insurance (OR, 2.70; 95% CI, 1.40-5.20) were more likely to complete a virtual visit compared with a telephone visit. Increasing age (OR per year, 0.98; 95% CI, 0.98-0.99) and being in the lowest median household income quartile (OR, 0.60; 95% CI, 0.42-0.86) were associated with lower odds of completing a virtual visit overall. Those patients within the second (OR, 0.53; 95% CI, 0.28-0.99) and lowest (OR, 0.33; 95% CI, 0.17-0.62) quartiles of median household income by census block and those with Medicaid, no insurance, or other public insurance (OR, 0.47; 95% CI, 0.23-0.94) were more likely to complete a telephone visit. Finally, being within the lower 2 quartiles of proportion being married (OR for third quartile, 0.49 [95% CI, 0.29-0.86]; OR for lowest quartile, 0.39 [95% CI, 0.23-0.67]) was associated with higher likelihood of a no-show visit.

Conclusions and Relevance

 These findings suggest that age, sex, median household income, insurance status, and marital status are associated with patient participation in telehealth. These findings identify vulnerable patient populations who may not engage with telehealth, yet still require medical care in a changing health care delivery landscape.

Figure. Percentage Distribution of Types of Visits During the Coronavirus Disease 2019 (COVID-19) Surge
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Table 1. Patient Characteristics Based on Visit Type From March 17 to May 1, 2020
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Table 2. Univariate and Multivariate Analysis of Virtual Visit Compared With All Other Visits
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Table 3. Univariate and Multivariate Analysis of Virtual Visit Compared With Telephone Visit
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Table 4. Univariate and Multivariate Analysis of Virtual Visit or Telephone Visit Compared With No-Show Visit
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Metformin use reduces risk of death for patients with COVID-19 and diabetes

Use of the diabetes drug metformin -- before a diagnosis of COVID-19 -- was associated with a threefold decrease in mortality in COVID-19 patients with Type 2 diabetes

UNIVERSITY OF ALABAMA AT BIRMINGHAM

Research News

 

IMAGE: ANATH SHALEV view more 

CREDIT: UAB

BIRMINGHAM, Ala. - Use of the diabetes drug metformin -- before a diagnosis of COVID-19 -- is associated with a threefold decrease in mortality in COVID-19 patients with Type 2 diabetes, according to a racially diverse study at the University of Alabama at Birmingham. Diabetes is a significant comorbidity for COVID-19.

"This beneficial effect remained, even after correcting for age, sex, race, obesity, and hypertension or chronic kidney disease and heart failure," said Anath Shalev, M.D., director of UAB's Comprehensive Diabetes Center and leader of the study.

"Since similar results have now been obtained in different populations from around the world -- including China, France and a UnitedHealthcare analysis -- this suggests that the observed reduction in mortality risk associated with metformin use in subjects with Type 2 diabetes and COVID-19 might be generalizable," Shalev said.

How metformin improves prognosis in the context of COVID-19 is not known, Shalev says. The UAB findings suggest that the mechanisms may go beyond any expected improvement in glycemic control or obesity, since neither body mass index, blood glucose nor hemoglobin A1C were lower in the metformin users who survived as compared to those who died.

"The mechanisms may involve metformin's previously described anti-inflammatory and anti-thrombotic effects," Shalev said.

The study -- first made available in MedRxiv and now published in the peer-reviewed journal Frontiers in Endocrinology -- included 25,326 patients tested for COVID-19 at the tertiary care UAB Hospital between Feb. 25 and June 22 of last year. Of the 604 patients found to be COVID-19-positive, 311 were African Americans.

The primary outcome in the study was mortality in COVID-19-positive subjects, and the potential association with subject characteristics or comorbidities was analyzed.

Researchers found that Blacks, who are only 26 percent of Alabama's population, were 52 percent of those who tested positive for COVID-19, and only 30 percent of those who tested negative. In contrast, only 36 percent of the COVID-19-positive subjects were white, while whites made up 56 percent of those who tested negative, further underlining the racial disparity. Once COVID-19-positive though, no significant racial difference in mortality was observed.

"In our cohort," Shalev said, "being African American appeared to be primarily a risk factor for contracting COVID-19, rather than for mortality. This suggests that any racial disparity observed is likely due to exposure risk and external socioeconomic factors, including access to proper health care."

Overall mortality for COVID-19-positive patients was 11 percent. The study found that 93 percent of deaths occurred in subjects over the age of 50, and being male or having high blood pressure was associated with a significantly elevated risk of death. Diabetes was associated with a dramatic increase in mortality, with an odds ratio of 3.62. Overall, 67 percent of deaths in the study occurred in subjects with diabetes.

The researchers looked at the effects of diabetes treatment on adverse COVID-19 outcomes, focusing on insulin and metformin as the two most common medications for Type 2 diabetes. They found that prior insulin use did not affect mortality risk.

However, prior metformin use was a different matter. Metformin use significantly reduced the odds of dying, and the 11 percent mortality for metformin users was not only comparable to that of the general COVID-19-positive population, it was dramatically lower than the 23 percent mortality for diabetes patients not on metformin.

After controlling for other covariates, age, sex and metformin use emerged as independent factors affecting COVID-19-related mortality. Interestingly, even after controlling for all these other covariates, death was significantly less likely -- with an odds ratio of 0.33 -- for Type 2 diabetes subjects taking metformin, compared with those who did not take metformin.

"These results suggest that, while diabetes is an independent risk factor for COVID-19-related mortality," Shalev said, "this risk is dramatically reduced in subjects taking metformin -- raising the possibility that metformin may provide a protective approach in this high-risk population."

The researchers say future studies will need to explore how metformin is protective, as well as assess the risks and benefits of metformin treatment and the indications for its use in the face of the ongoing COVID-19 pandemic.

###

This study is part of a new Precision Diabetes Program, a collaboration between the UAB Comprehensive Diabetes Center and the Hugh Kaul Precision Medicine Institute at UAB.

Co-authors with Shalev for the paper, "Metformin use is associated with reduced mortality in a diverse population with COVID-19 and diabetes," are Andrew B. Crouse and Matthew Might, the Hugh Kaul Precision Medicine Institute at UAB; Tiffany Grimes and Fernando Ovalle, the Comprehensive Diabetes Center and the Department of Medicine Division of Endocrinology, Diabetes and Metabolism at UAB; and Peng Li, UAB School of Nursing.

Support came from National Institutes of Health grants DK078752, DK120379 and TR001417.

Shalev is a professor in the UAB Department of Medicine Division of Endocrinology, Diabetes and Metabolism, and she holds the Nancy R. and Eugene C. Gwaltney Family Endowed Chair in Juvenile Diabetes Research.

 

New study: Without right messaging, masks could lead to more COVID-19 spread

UNIVERSITY OF VERMONT

Research News

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IMAGE: A NOVEL STUDY SUGGESTS THAT THE BEHAVIOR PUBLIC OFFICIALS ARE NOW MANDATING OR RECOMMENDING UNEQUIVOCALLY TO SLOW THE SPREAD OF COVID-19--WEARING A FACE COVERING--SHOULD COME WITH A CAVEAT. IF NOT... view more 

CREDIT: JOSHUA BROWN

A novel new study suggests that the behavior public officials are now mandating or recommending unequivocally to slow the spread of surging COVID-19--wearing a face covering--should come with a caveat. If not accompanied by proper public education, the practice could lead to more infections.

The finding is part of an unique study, just published in JMIR Public Health and Surveillance, that was conducted by a team of health economists and public health faculty at the University of Vermont's Larner College of Medicine in partnership with public health officials for the state of Vermont.

The study combines survey data gathered from adults living in northwestern Vermont with test results that showed whether a subset of them had contracted COVID-19, a dual research approach that few COVID studies have employed. By correlating the two data sets, researchers were able to determine what behaviors and circumstances increased respondents' risk of becoming sick.

The key risk factor driving transmission of the disease, the study found, was the number of daily contacts participants had with other adults and seniors.

That had relevance for two other findings.

Those who wore masks had more of these daily contacts compared with those who didn't, and a higher proportion contracted the virus as a result.

Basic human psychology could be at work, said Eline van den Broek-Altenburg, an assistant professor and vice chair for Population Health Science in the Department of Radiology at the Larner College of Medicine and the study's principal investigator.

"When you wear a mask, you may have a deceptive sense of being protected and have more interactions with other people," she said.

The public health implications are clear. "Messaging that people need to wear a mask is essential, but insufficient," she said. "It should go hand in hand with education that masks don't give you a free pass to see as many people as you want. You still need to strictly limit your contacts."

Public education messaging should make clear how to wear a mask safely to limit infection, van den Broek-Altenburg added.

The study also found that participants' living environment determined how many contacts they had and affected their probability of becoming infected. A higher proportion of those living in apartments were infected with the virus compared with those who lived in single family homes.

"If you live in an apartment, you're going to see more people on a daily basis than if you live in a single family home, so you need to be as vigilant about social distancing," van den Broek-Altenburg said.

The study controlled for profession to prevent essential workers, who by definition have more contacts and are usually required to wear masks, from skewing the results.

"It's generally known that essential workers are at higher risk, and our study bore that out," van den Broek-Altenburg said. "We wanted to see what else predicted that people were going to get sick," she said.

Reported cases in Chittenden County, Vermont only one-fifth of likely total

The study provides the first estimate of unreported cases in Vermont's Chittenden County, where most study participants live. The survey found that 2.2 percent of the survey group had contracted the virus, suggesting that an estimated 3,621 Chittenden County residents were likely to have become ill, compared with just 662 reported cases, just 18%.

That figure translates to a hospitalization rate of 1.2% and adjusted infection fatality rate of 0.55%.

This finding is important for policy-makers, van den Broek-Altenburg said, in and out of Vermont.

"If you know how many people are sick or have been sick, you're much better equipped to make precise predictions of will happen in the future and fashion the appropriate policies," she said.

It also shows the importance of serologic and PCR testing of the general population, she said.

"If you only test symptomatic patients, you'll never be able to find out how many people have already had the virus. With our random sample study we were able to show that Vermont has so far only tested less than one-fifth of the people who have likely had the virus. To capture the larger population, random samples of the population are needed so we can also capture asymptomatic patients, which appears to be the majority of COVID-19 cases."

The study, among other things, is a proof of concept, van den Broek-Altenburg said.

"I hope it leads to other, larger studies that combine survey data with widespread testing. This approach is essential to both understanding the dynamics of this pandemic and planning our response to futures ones."

Ten of the 454 survey respondents who took the serologic test had antibodies for Covid-19, and one tested positive for the virus. Given the small number, researchers simplified their models and were able to reach a high confidence level in the two key findings.

"We tested our models and found that the results were robust through several different model specifications," van den Broek-Altenburg said.

To create the study group, the researchers sent a survey to 12,000 randomly selected people between the ages 18 and 70 who had at least one primary care visit at the University of Vermont Medical Center, which services primarily northwestern Vermont, in the past three years.