Tech

New hope for COPD patients possible with in-home device

ROCHESTER, Minn. -- In a new paper published Feb. 4 in JAMA, Mayo Clinic researchers describe the benefits of in-home noninvasive ventilation therapy ? which includes a type referred to as bilevel positive airway pressure, or BiPAP ? for many patients with chronic obstructive pulmonary disease (COPD). The team identified a number of benefits, including reduced mortality, fewer hospital admissions, lower risk of intubation, improved shortness of breath, and fewer emergency department visits.

COPD is a chronic lung disease that makes it difficult to breathe. COPD is the third leading cause of death in the U.S., with more than 15 million people currently living with the disease, according to the American Lung Association.

Many people who have COPD suffer from hypercapnia, the retention of carbon dioxide -- a waste product of metabolism normally expelled by the lungs as a person breathes. This may lead to acute respiratory failure and hospitalization. One treatment for chronic hypercapnia is noninvasive ventilation, or a machine with a mask that helps to improve breathing.

Michael Wilson, M.D., a pulmonary and critical care physician at Mayo Clinic, led the study, which was funded by the Agency for Healthcare Research and Quality under a contract with the Mayo Clinic Evidence-Based Practice Center.

"Although there is ample evidence supporting in-hospital use of breathing devices such as BiPAP, until now, we didn't know which benefits may be available when we send people home with a new piece of equipment," says Dr. Wilson. "There were indications that at-home therapy might be beneficial, but there were conflicting studies and guidelines as to what would be best for our patients."

He and his colleagues wanted to determine the best practice, collecting and summarizing all available medical knowledge surrounding the topic.

To that end, the team conducted a meta-analysis, combing all available peer-reviewed and other expert literature for relevant randomized clinical trials and comparative observational studies.

After reviewing more than 6,300 citations, the researchers found 33 studies evaluating outcomes for 51,085 patients with COPD and hypercapnia who were followed for at least one month while using a noninvasive ventilator at home during nighttime sleeping hours.

Among these patients, use of a noninvasive ventilator device, such as bilevel positive airway pressure, compared to no device was significantly associated with lower mortality: 29.2% versus 22.3%. The use of a noninvasive ventilator device also led to fewer emergency department visits and hospitalizations, and lower rates of intubation if patients were admitted to the hospital.

"While there does seem to be some clear benefits to using devices such as BiPAP, we should be cautious as the studies included a lot of different types of patients with COPD. And many of the studies we evaluated were low or moderate in quality," says Dr. Wilson. "We still have a lot more to learn about which machine settings are best for different types of patients. In addition, although many studies in our review included quality of life measurements, we didn't see an improvement. While some studies showed better quality of life, other studies showed no difference. Again, this points to the importance of needing to more carefully evaluate which patients with COPD may receive benefit."

"Patients with COPD should talk with their physicians to determine whether a breathing device such as a BiPAP machine might be a good choice for them," he says. "For many patients, such a device may offer important benefits."

Credit: 
Mayo Clinic

Shelter, safest air intake locations during urban pollution events identified

Roofs and the downwind sides of buildings in street canyons have the lowest levels of particulate matter during a single-source pollution event, according to Penn State researchers. The findings have implications for improving evacuation plans during a pollution release as well as for informing ventilation system design of urban buildings.

"Previous research has focused on ambient pollution created by traffic," said Jeremy Gernand, assistant professor of industrial health and safety. "We decided to investigate sources of pollution from a point source of particulate matter, such as a chemical spill or an accidental release from a factory."

The researchers investigated a pollutant release scenario to evaluate the safest locations for evacuation and for building design elements such as air intakes. This marks the first study investigating an emission event from a single source near a street canyon.

Monitoring air quality in urban areas can be very important due to high population density and levels of particulates. Street canyons, or places where the street is bounded on both sides by buildings, are important locations for studying air pollution because they are prevalent in urban areas.

Particulates, often referred to as aerosols, are fine solids or liquid droplets suspended in gas. High concentrations in the atmosphere can contribute to mortality rates, because exposure to these particles can exacerbate or cause adverse medical effects. Particulates are released from a variety of natural or human sources, such as cars, construction sites and dust storms.

Researchers in Penn State's Mining Ventilation Laboratory created a 3D miniature street canyon in a wind tunnel using foam blocks to simulate buildings . Four foam blocks were placed in a two-by-two array, separated by gaps that served as streets.

To ensure the airflow within the wind tunnel matched realistic conditions in an urban area, researchers had to make adjustments. Typically, air in a wind tunnel exhibits laminar flow, meaning it flows smoothly in parallel layers with no eddies or crosscurrents that disrupt the direction of flow. This type of flow can be ideal for testing mechanisms such as airplane wings in simulated high-altitude air.

At lower elevations, however, air behaves very differently. Near the ground, smaller structures like houses and trees and larger buildings, such as skyscrapers, interrupt the smooth flow of air and cause it to become turbulent, or irregular and agitated.

The researchers used low-cost materials like Legos and cardboard spires to create turbulent airflow in a wind tunnel filled with laminar-flowing air.

To simulate a single particulate emission source, researchers used water generated from an ultrasonic humidifier. Because environmental particulates are frequently coated in water, the collisions between water droplets in a wind tunnel experiment and collisions between water-coated particulates outside can be very similar, Gernand said.

To find the areas in the street canyon where particulate levels reached their minimum and maximum concentrations, researchers used the data from the wind-tunnel experiment to create a computer model of the scenario. Computer simulations showed the lowest particulate concentrations were located at the roof and on downwind building facades. At breathing level, the lowest concentrations were found on the leeward -- protected -- side of the array's transverse channel, the street running perpendicular to the direction of airflow.

The findings have implications for improving evacuation plans and for informing ventilation system design. In the event of a pollution release emergency from a central source, pedestrians should be evacuated to the leeward side of the transverse channel. For installation of new air intakes, portions of roofs furthest away from inner channels, or roads, of street canyons serve as the safest location, the researchers said.

The researchers reported their findings in the journal Air Quality, Atmosphere and Health.

However, given the variety of possible scenarios, these findings represent only a general guideline and will benefit from further investigation, said Gernand. Building upon the cost-effective modeling approach used in this study, future research will consider additional possibilities with the goal of providing more comprehensive safety recommendations.

Credit: 
Penn State

Wasps' gut microbes help them -- and their offspring -- survive pesticides

Exposure to the widely used pesticide atrazine leads to heritable changes in the gut microbiome of wasps, finds a study publishing February 4 in the journal Cell Host & Microbe. Additionally, the altered microbiome confers atrazine resistance, which is inherited across successive generations not exposed to the pesticide.

"After a single exposure to some chemicals--xenobiotics--the gut microbiome can be permanently affected," says senior study author Robert Brucker of Harvard University. "Exposure can have lasting changes to future generations even after an exposure risk is eliminated."

Agrochemicals used to fertilize crops and control pest species pose one of the greatest xenobiotic exposure risks to many organisms. The herbicide atrazine is the second most sold pesticide globally. Previous studies have shown that atrazine has multiple effects on host animals, but little is known about how environmental xenobiotic chemicals change the gut microbiome.

To address this question, Brucker and his team examined the impact of acute or continuous subtoxic atrazine exposure on the model wasp species Nasonia vitripennis across 36 generations. Analysis of the transcriptome and proteome of the wasps revealed that exposure to 300 parts per billion (ppb) of atrazine--similar to the concentration encountered by pollinators in newly sprayed agricultural fields and streams--may alter N. vitripennis immunity, mitochondrial function, and behavior.

In the first generation, exposure to 300 ppb of atrazine altered the bacterial community structure of wasps, resulting in an increase in microbiome diversity and overall bacterial load. Even exposure to a lower concentration of 30 ppb of atrazine caused a microbiome shift that persisted across successive generations.

When the researchers switched the offspring of the atrazine-exposed population to a non-atrazine diet for six generations, they observed that the bacterial microbiome remained most similar to that of the parents. "This result indicates that the disruption to the microbiome after acute exposure to atrazine is inherited across generations, even after exposure is removed," Brucker says.

In addition, exposure to 30 ppb of atrazine over 36 generations reduced atrazine-induced mortality by a factor of ten, and also increased tolerance to the herbicide glyphosate, despite no prior exposure to the compound. After 25 generations, a subset of the wasp population was switched to a non-atrazine diet. Remarkably, atrazine tolerance was inherited and sustained through the 36th generation.

Other experiments showed that the increased atrazine tolerance of wasps is related to their altered microbiome. For example, maintaining wasps in a germ-free environment eliminated atrazine tolerance. On the other hand, transplanting the microbiome of atrazine-exposed wasps to non-exposed wasps conferred atrazine resistance.

"Overall, we demonstrate that resistance to multiple pesticides can arise in a population that is exposed to sub-toxic concentrations, that the microbiome facilitates this resistance, and that it provides resistance against other pesticides to which the host animal has never been previously exposed," Brucker says.

In particular, atrazine exposure increased the densities of the rare gut bacteria Serratia marcescens and Pseudomonas protegens. Feeding these atrazine-degrading bacteria to wasps that had not been exposed to atrazine resulted in resistance to this pesticide.

"The shift in the microbial community following continuous atrazine exposure may be providing host resistance via detoxification, representing a rapid route of ecological adaptation for the host to cope with novel toxic challenges," Brucker says. "Pesticide exposure causes functional, inherited changes in the microbiome that should be considered when assessing xenobiotic exposure and as potential countermeasures to toxicity."

Taken together, the findings demonstrate that atrazine exposure can alter the microbial community of wasps, which can in turn directly impact host fitness across generations. Even though Nasonia wasps are not natural crop pollinators, the study could have broad implications. Wild populations of pollinators have been exposed to atrazine since the 1950s, the equivalent of dozens of generations. Notably, bacterial atrazine-metabolizing genes are also present in wild bee populations exposed to the pesticide.

"These results could reflect microbe-host-associated changes in response to xenobiotic exposure in wild honey bee population, similar to what we describe in Nasonia and considering the decades of habitual exposure, and adaptation within pollinator populations are likely to have already occurred," Brucker says. "Ultimately, these effects could have repercussions on host behavior, metabolic stress, immunocompetence, and host-microbiota regulation."

In future studies, Brucker and his team plan to examine which loci have been under selection, and how they might be implicated in toxin resistance or microbiome regulation. They are also planning on leveraging their findings to develop probiotics for honey bees to reduce multi-pesticide exposure risk.

"We can use our understanding of the host-microbiome interaction to reduce the exposure risk of all pesticides, for example, by using bacteria for cleaning up spills or as probiotics for at-risk humans, or off-target plants and animals," Brucker says. "Further host-microbiome studies of multi-generational exposure to xenobiotic compounds are needed, especially in light of the increased risk of xenobiotic exposure to humans, plants, animals, fungi, and bacteria across the globe."

Credit: 
Cell Press

New discovery provides hope for improved multiple sclerosis therapies

Scientists from Trinity College Dublin have made an important discovery that could lead to more effective treatments for people living with multiple sclerosis (MS) and other autoimmune diseases such as psoriasis and rheumatoid arthritis. Their work highlights the significant potential of drugs targeting a specific immune molecule (IL-17) implicated in MS.

The scientists, led by Kingston Mills, Professor of Experimental Immunology, and Aoife McGinley, Postdoctoral Fellow, in Trinity's School of Biochemistry and Immunology have published their results today [Tuesday 4th February 2020] in the prestigious Cell press journal, Immunity.

Multiple sclerosis (MS) is a debilitating disease that affects around 2.3 million people globally and over 9,000 people in Ireland. It is associated with infiltration of immune cells into the brain and spinal cord that cause damage to nerves, leading to neurological disabilities.

However, the cause and precise immunological basis to this autoimmune disease is still unclear.

Studies in a mouse model of MS, called experimental autoimmune encephalomyelitis (EAE), have shown that immune 'T cells', which secrete an immune molecule called 'IL-17', cause damage to the myelin sheath that surrounds nerves in the central nervous system (CNS).

Early clinical trials with antibody-based drugs that block IL-17 are showing promise in the treatment of relapsing-remitting (RR) MS and have already been licensed for the treatment of psoriasis, another common autoimmune disease.

The just-published study from Professor Mills' research group outlines an entirely new role for IL-17 in EAE and, potentially, in MS.

Professor Mills said:

"Our team found that IL-17 plays a critical 'priming' role in kick-starting the disease-causing immune response that mediates the damage in EAE and MS."

"The new research shows that, instead of playing a direct part in CNS pathology, a key role of IL-17 is to mobilise and activate an army of disease-causing immune cells in the lymph nodes that then migrate to the CNS to cause the nerve damage."

Dr Aoife McGinley added:

"Crucially, our findings suggest that drugs that block IL-17 may not need to get across the blood-brain-barrier to be effective in treating MS."

"So, as well as shedding new light on the importance of IL-17 as a drugs target in RR MS, our research highlights the huge potential of drugs that block IL-17 in the treatment of other autoimmune diseases, such as psoriasis and rheumatoid arthritis."

Credit: 
Trinity College Dublin

Size matters! What drives zoo attendance and how does footfall impact conservation?

video: Size matters! What drives footfall to zoos, and how much of a difference to they make to conservation?

Image: 
Trinity College Dublin.

Scientists from Trinity College Dublin, Species360 and NUI Galway have quantified what drives attendance to zoos by assessing how variations in animal collections affect footfall. Crucially, they link their findings to the contributions made to conservation efforts in situ (in the wild), and find that zoos are making significant, positive impacts on our attempts to conserve biodiversity as our planet enters its sixth mass extinction.

Among the headline findings are that zoos with lots of animals, lots of different species (particularly mammals), and with large animals such as elephants, tigers and pandas attract higher numbers of visitors. It is difficult for zoos to fulfil all of these requirements simultaneously however as large animals take up a lot of space and resources meaning relatively few can be accommodated.

The research found that instead of a "one size fits all" approach to a zoo collection there are several different strategies that can be used to encourage attendance, including the inclusion of unusual animals. Ultimately higher numbers of visitors led to zoos contributing more conservation activity in the wild.

This research used a global data-set for 458 zoos in 58 countries, including species holdings data from the Zoological Information Management System (ZIMS) managed by Species360. More than 1,200 wildlife institutions curate and share animal data as members of Species360, contributing real-time demographic, medical, genetic, and population insights for more than 22,000 species and 10,000,000 individual animals, both living and historic.

The research has been published today [Tuesday 4th February 2020] in leading international journal, Nature Communications.

Andrew Mooney, PhD Candidate in Trinity's School of Natural Sciences, is first author on the paper. He said:

"Zoos and aquariums not only breed and maintain populations of thousands of wildlife species but they also act as centres for public education, wildlife rehabilitation, scientific research and public entertainment. Zoos and aquariums attract more than 700 million people annually around the world and thus they provide an unparalleled audience for conservation education."

"Housing large, charismatic animals in zoos and aquariums is being questioned more and more from an ethical perspective, but our research concludes that these animals do not solely play an entertainment role but also serve a broader conservation purpose by indirectly increasing in situ project investment."

Key Results

Larger animals are associated with greater attendance

Lots of animals (rather than a few) are associated with greater attendance

Zoos find it difficult to maximise both large animals and lots of them at the same time

Unique collections of animals are associated with greater attendance, but not to a huge degree

Zoo size (on its own) has no impact on attendance (although smaller zoos can house fewer animals, and fewer large animals...)

Zoos closer to large populations of people enjoy greater attendance

Greater attendance results in greater conservation contributions in the wild

Zoos with more conservation-threatened animals invest more conservation projects in the wild (gold standard)

Yvonne Buckley, Professor of Zoology at Trinity College Dublin, added:

"Conserving species in the wild remains the gold standard and with multiple habitats and species coming under ever-more serious threats from a variety of angles, there is an increasing relevance and importance to the role played by the thousands of zoos and aquariums across the globe in supporting conservation in the wild."

"Our study provides global evidence to suggest that zoos don't need to compromise their economic viability and entertainment value in order to have a significant value to conservation."

Credit: 
Trinity College Dublin

A never-before described natural process in soil can convert nitrogen gases into nitrates

Researchers from the Higher Technical School of Agricultural Engineering at the University of Seville, together with a group of international experts, have just published a scientific article in which they demonstrate that some soil minerals can convert the nitrogen gases NO + NO2 (NOX) into nitrates by means of visible and ultraviolet radiation. This natural process had not previously been described and demonstrates, according to the data obtained, that solar light seems to be the missing piece in the puzzle of the nitrogen cycle in soil.

"This finding is important, not only because it involves a never-before described natural process, as we have said, but also because the nitrogen in the soil is crucial for global sustainability, as it affects the productivity of the ecosystem and air quality for living organisms, including humans. In addition, nitrogen is connected to the emission of greenhouse gases (GHG) and global warming. It is worth highlighting that NO in soil is the main precursor of N2O, an important GHG", reports the University of Seville teacher and author of the study, Antonio Delgado.

Despite the basic processes in the nitrogen cycle in nature being known for more than a hundred year, in this article, some photocatalytic mechanisms are proposed that were previously unknown. The project shows that solar radiation (especially ultraviolet) can activate soil minerals, so generating reactive types of oxygen (free radicals) that can transform NOx gases into nitrates, and vice versa.

How to maximise the functions of agricultural soil

Parallel to this finding, the research group led by Delgado, has collaborated on the development of a decision-making tool for the improvement of soil function in agriculture. This tool, which is currently available in various languages of the European Union and which will soon be translated into Spanish and adapted to the conditions in Spain, makes it possible for farmers and technicians to choose the best options for maximising each of the five soil functions: productivity, nutrient recycling, water purification and regulation, biodiversity and mitigation of climate change. This tool will also be useful for making policy decisions that affect how current social demand can be met by agriculture. In the tool, in which data regarding soil, climate, and agricultural-exploitation management must be included, the most advisable options for maximising the five soil functions appear.

'Soilnavigator' is one of the most important results of the European project LAND Management: Assessment, Research, Knowledge base (LANDMARK). Within this project, a scientific framework has been drawn up for legislators that can serve as a base for the preparation of valid regulations for all of Europe. Twenty-two institutions from 14 European countries, as well as Switzerland, Brazil and China, participated in the project.

Credit: 
University of Seville

Fast screening for potential new catalysts

image: Michael Meischein, Tobias Löffler, Wolfgang Schuhmann, Alan Savan and Alfred Ludwig (from the left)

Image: 
RUB, Marquard

It helps to directly ascertain the potential of a possible alloy. The team reports in the journal Angewandte Chemie International Edition on 22 December 2019.

Efficient catalysts made from inexpensive and available elements

The researchers' hopes with regard to new catalysts made from inexpensive and available elements rest on what are known as complex solid solutions, also called high-entropy alloys. They consist of five or more elements that are homogeneously mixed and the diverse, complex interactions of which enable fine adjustments of the relevant properties. Importantly, it is not only the properties of the individual elements that are crucial but above all their interaction. "This opens up a wide range of otherwise unachievable possibilities in order to simultaneously optimise price and performance for possible applications," says Professor Wolfgang Schuhmann from the Center for Electrochemical Sciences at RUB.

However, fundamental knowledge about the recently discovered new catalyst class is still lacking. What information could be provided by measurements in order to make targeted advances in catalyst development? How does this help find the right one among the almost infinite possible combinations? What effect does replacing an element have on the properties?

Interpreting results more accurately

"We have developed a concept that enables us to understand the correlations between the selection of the elements, theoretical, activity-defining properties, and actually measurable parameters," reports Tobias Löffler, a doctoral candidate in electrochemistry. As the complex solid solutions differ from conventional electrocatalysts in all these points, this understanding is fundamental for experimental progress.

The researchers are thus faced with the challenge that not only the combination of elements but also the proportion of each element is crucial and any deviations change the properties. "We show how experiments with an alloy made from, for instance, five equal parts of each element can be interpreted in order to identify the element combination as potentially active," explains Tobias Löffler. The researchers are thus able to identify quickly whether it is worthwhile optimising the proportions of the elements. "This enables us to reduce the screening workload for possible material compositions to a fraction without overlooking promising candidates," explains Wolfgang Schuhmann. Without this knowledge, it is possible that combinations could be filtered out using conventional evaluations even though these could be highly interesting if the element ratios were optimised. "What's more, this concept forms a cornerstone in understanding the complex mode of action of this material class, which helps to better understand the possible parameters that can be adjusted and thus derive promising design concepts from this."

Encouraging researchers

The researchers tested these conceptual considerations with selected alloys using the oxygen reduction reaction relevant to fuel cells. They were able to demonstrate in which cases replacing or adding an element to an existing element combination has a positive effect and vice versa. They were also able to identify combinations that are suitable for further optimisation.

"For material synthesis, this means an immense saving in time and money," says Professor Alfred Ludwig, Chair for Materials Discovery and Interfaces at RUB. "Producing and analysing all of the possible element ratios of an alloy consisting of five elements is a huge challenge. By eliminating elementary hurdles, we hope to further facilitate access to this highly topical and technological relevant field and encourage more researchers to contribute with their respective skills."

Credit: 
Ruhr-University Bochum

Red coral effectively recovers in Mediterranean protected areas

image: These are red corals in the Mediterranean Sea.

Image: 
@Aldo Ferrucci

Protection measures of the Marine Protected Areas have enable red coral colonies (Corallium rubrum) to recover partially in the Mediterranean Sea, reaching health levels similar to those of the 1980s in Catalonia and of the 1960s in the Ligurian Sea (Northwestern Italy). This is shown in a recent study carried out by researchers from the Institute of Environmental Science and Technology of the Universitat Autònoma de Barcelona (ICTA-UAB) that highlights the effectiveness of marine protections actions and recalls that the disappearance of red coral in the last decades has drastic consequences on its capacity to sequester sea carbon, and also to maintain complexity in its habitat, resulting in lower biodiversity.

Based on historical red coral data from the Northwestern Mediterranean Sea, the ICTA-UAB study documents how these colonies reached their minimum health status (the capacity of perpetuation of future generations, avoiding local extinction) in the decade of the 1990s, when the larger tree-like colonies were depleted due to their overexploitation. Although the implemented protection measures have proven to be effective, "these results have to be treated with caution, as they only reflect a part of the existing red coral population of the region", explains lead author of the study Miguel Mallo, who states that "in the most recent decades, the vast majority of red coral studies, and thus, data available, were concentrated in few areas coinciding with Marine Protected Areas, leaving unstudied the colonies of other locations that do not benefit from protection measures, with worse health status".

Results from this work also present the dynamics of the carbon sequestration capacity of red coral, being halved in only a few decades and thus highlighting the consequences of direct harvesting of this slow growing species. "The very slow growth and low reproductive rates of red coral, combined with its continuous harvest and intense periods of overexploitation, makes the majority of the actual red coral small in size and unable to do its function in the habitat, thereby affecting several species", highlights Sergio Rossi.

The Mediterranean Sea is considered one of the main marine biodiversity hotspots worldwide, as well as one of the most pressured seas by human activities since ancient times. Most of the impacts are concentrated where the highest amount of marine biodiversity exists: on the coastal marine habitats within the zone that sunlight penetrates.

The main habitat representatives of such biodiversity are the seagrass meadows and the coralligenous: calcareous formations of encrusting corals and algae. Iconic Mediterranean species such as red coral, a cnidarian semi-endemic of the Mediterranean, with a hard and striking red skeleton, is key for these habitats, as it gives it physical structure, increases its complexity and serves as protection for several species that feed on the coralligenous habitat. It is comparable to the function that trees have in forests.

Unfortunately, since ancient times (the oldest evidence of its use by humans dates back 30,000 years), numerous civilizations have used the precious red coral skeleton to make jewels, ornaments, and trade; some even believed that when ingested, the red coral could increase fertility, healing or other spiritual endeavours. The main disadvantage suffered by this species is its commercial value and indeed, its historically heavy harvesting for the jewellery sector.

The type of data used for this historical ecological study were obtained from multiple sources (quantitative and qualitative, academic and non-academic) conducted through the internet and libraries, especially in the Biblioteca Carles Bas i Peired (CSIC-CMIMA, Barcelona) and the Bibliothèque du Laboratoire Arago (BUPMC, Banyuls-sur-mer).

"This work stresses once more the urgent need of protection measures in Mediterranean marine biodiversity hotspot areas, to improve the resilience and adaptation of key endemic systems. The positive note is that the protection measures can be effective relatively quickly. This is important because it gives to these ecosystems greater capacity to resist and recover following climate events in this rapidly changing Mediterranean Sea", ICTA-UAB researcher Patrizia Ziveri commented. In addition, this new data also shows the contribution of red coral to carbon storage and the consequences that their disappearance has on increasing atmospheric carbon emission.

Credit: 
Universitat Autonoma de Barcelona

More pieces of the autism puzzle uncovered

A major international study from the Autism Sequencing Consortium with participation of researchers from the Danish iPSYCH psychiatry project, has recently mapped 102 new autism genes. The new findings provide a new understanding of the biology behind autism, which could in the future be utilised to provide an earlier and more precise diagnosis and better treatment options.

Ever since the first autism diagnosis was made in 1938, researchers have been trying to clarify where the disorder originates. There have been many suggestions - along with many disagreements. But one thing has been clear for a while: Genetics play a major role with a heritability of up to eighty per cent.

The largest study so far of rare genetic variants has now identified 102 new so-called risk genes for autism. The results have just been published in the international journal Cell.

"Broadly speaking, there are two types of genetic variants which play a role in autism. There are uncommon genetic variants that few people have, although these may have a big effect, and then there are frequent variants which we all carry some of, and which each contribute in a very small way to the risk," says Associate Professor Jakob Grove from Aarhus University, who is one of the driving forces behind the Danish contribution and a member of the iPSYCH research project.

Better treatment in sight

In the study, the researchers mapped the DNA building blocks in the genes of 35,584 individuals, of whom 11,986 had autism. The researchers then determined how many times each gene is affected by variants with "protein disrupting consequences", as the researcher puts it. "If a gene is more often hit by these mutations among people with autism than among people without it, this indicates that the gene is involved in the processes that lead to autism, and is thus designated as a risk gene," explains Jakob Grove. The majority of the identified gene-destroying mutations are new mutations that are only found in the person with autism and not in their parents.

The genetic findings provide an entirely new insight into the biological processes that are involved in the development of autism. Some of the genes identified alter early development broadly, while others appear to be more specific to autism. Most of the genes help determine how neurones communicate with each other or they regulate the expression of other genes.

"This new knowledge could provide a better basis for understanding autism. For example, it may help us to make a diagnosis earlier, which we already know makes life easier for people with autism and their relatives. It's also conceivable it could contribute to the development of personalised medicine for those who may want this," says Jakob Grove. In other words, the results of the study may turn out to be crucial for the treatment of psychiatric disorders in the future.

However, he also emphasises that the new findings can only explain a few cases of autism as these genetic variants are only present in few individuals. "For this reason, iPSYCH continues to study both rare and more frequent genetic variants," he says.

Credit: 
Aarhus University

High-tech printing may help eliminate painful shots

image: This microneedle array has backward-facing barbs that interlock with tissue when inserted, enhancing adhesion.

Image: 
Riddish Morde

Painful hypodermic needles may not be needed in the future to give shots, inject drugs and get blood samples.

With 4D printing, Rutgers engineers have created tiny needles that mimic parasites that attach to tissues and could replace hypodermic needles, according to a study in the journal Advanced Functional Materials.

While 3D printing builds objects layer by layer, 4D goes further with smart materials that are programmed to change shape after printing. Time is the fourth dimension that allows materials to morph into new shapes.

"We think our 4D-printed microneedle array will allow for more robust and sustained use of minimally invasive, pain-free and easy-to-use microneedles for delivering drugs, healing wounds, biosensing and other soft tissue applications," said senior author Howon Lee, an assistant professor in the Department of Mechanical and Aerospace Engineering in the School of Engineering at Rutgers University-New Brunswick.

This YouTube video by Riddish Morde shows microneedles applied to chicken muscle tissue.

YouTube video by Daehoon Han on 4D printing of a bio-inspired microneedle with backward-facing barbs for enhanced tissue adhesion.

Hypodermic needles are widely used in hospitals and labs to extract blood and inject drugs, causing pain, scarring skin and posing an infection risk. People with diabetes often take blood samples multiple times a day with needles to monitor blood sugar levels.

Microneedles (miniaturized needles) are gaining attention because they are short, thin and minimally invasive, reduce pain and the risk of infection and are easy-to-use. But their weak adhesion to tissues is a major challenge for controlled drug delivery over the long run or for biosensing, which involves using a device to detect DNA, enzymes, antibodies and other health indicators.

In nature, some insects and other organisms have developed microscopic features that adhere to tissue, such as the microhooks of parasites, barbed stingers of honeybees and scaled quills of porcupines. Inspired by these examples, Rutgers engineers developed a microneedle that interlocks with tissue when inserted, enhancing adhesion. They combined a micro 3D-printing technique and a 4D-printing approach to create backward-facing barbs on a microneedle.

Using chicken muscle tissue as a model, the researchers showed that tissue adhesion with their microneedle is 18 times stronger than with a barbless microneedle. Their creation outperforms previously reported examples, resulting in more stable and robust drug delivery, collection of bio-fluids and biosensing, the study says.

Credit: 
Rutgers University

Grooves hold promise for sophisticated healing

image: A microCT image shows a 3D-printed scaffold with clear grooves meant for the deposition of live cells. The grooved lines hold ink deposited during the printing process. Scaffolds can be made in any shape, based on medical images, to fill the site of a wound.

Image: 
Rice Biomaterials Lab

HOUSTON - (Feb. 4, 2020) - Who ever said bioengineers can't get their groove on?
The Rice University team led by Antonios Mikos says otherwise with its development of a groovy method to seed sophisticated, 3D-printed tissue-engineering scaffolds with living cells to help heal injuries.

The researchers are literally carving grooves into plastic threads used to build the scaffolds. The grooves are then seeded with cells or other bioactive agents that encourage the growth of new tissue.

The strategy protects cells from the heat and shear stresses that would likely kill them in other scaffold fabrication processes. It also provides a way to layer cells that ultimately become different kinds of tissue, like bone and cartilage, in a mechanically stable platform.

The beauty of it is the 3D printer cuts the grooves into a thermoplastic, inserts the cells at the proper temperature and creates a three-dimensional implant, based on medical images, in a single process.

The research is the topic of a paper in Bioprinting.

Unlike cell-supporting hydrogel scaffolds under development at Rice and elsewhere, this process creates hard implants that would be surgically inserted to heal bone, cartilage or muscle, Mikos said. Like hydrogels, the biocompatible implants would degrade over time and leave only natural tissue.

"The major innovation here is our ability to spatially load a scaffold that is 3D printed with different cell populations and with different bioactive molecules," Mikos said.

Until now, 3D-printed scaffolds were generally seeded with uniform distributions of cells, he said. "If we wanted different cell populations at different points in the scaffold, we could not do that. Now we can."

"The fibers are cylinders that we engrave with a needle to give it a groove as it's printing," said Rice research scientist Maryam Elizondo, co-lead author of the paper with alumnus Luis Diaz-Gomez. Once the groove is set and cooled just enough, the printer then deposits a cell-infused ink. "We do that for every fiber for every layer of the scaffold."

Elizondo compared the grooved threads, which are about 800 microns wide, to taco shells that keep the contents inside without spilling; here, the addition of grooves and ultraviolet-activated crosslinkers keep the cell ink inside. She said it takes about half an hour to completely print a thumbnail-sized implant.

Mikos said the scaffold isn't limited to cells. "We can also load different growth factors on different levels," he said. "Very high temperatures would deactivate them, but here we can deposit growth factor-loaded microparticles inside the grooves as they cool. That would preserve the bioactivity of the molecule.

"This is a great success for the Center for Engineering Complex Tissues," he said of the multiuniversity collaborative he helped create. "That was the goal when we built the center: to develop advanced materials with unique properties that can be used for tissue engineering applications that address unmet clinical needs. And this is a perfect example."

Credit: 
Rice University

Wildfires increase winter snowpack -- but that isn't necessarily a good thing

Deep in the Tushar mountains, some three hours south of Brigham Young University's campus in Utah, Ph.D. student Jordan Maxwell and two other students found themselves in deep snow, both literally and figuratively.

It was December 2014 and the students had just started field work under the tutelage of BYU forest ecologist Sam St. Clair for research on the impact of wildfires on snowpack levels. Unfortunately, the snowmobiles they'd been using could go no further and there were still dozens of measurements they needed to take.

"So, we put on our skis and got to work," Maxwell said.

The students would go on to log between 15 and 20 miles of back-country skiing each day in the field, measuring snow depth levels and snow water equivalency at 30 sampling spots within the footprint of the Twitchell Canyon Fire, a 2010 mega-fire that consumed 45,000 acres and was the largest active wildfire in the United States at the time.

The team also measured the presence, height and diameter of trees at each location and whether or not those trees were killed by the fire. After crunching the data, collected over that winter and the next, they found pretty impressive numbers: there was an 85% greater snow depth in areas that burned completely compared to areas that didn't burn at all.

"Fires mean more snow into the system initially because of reduced trees that usually block and hold the snow temporarily on branches," said St. Clair, a professor of plant and wildlife sciences. "It's a really good outcome for north-facing slopes where the snowpack will hold in the shade, but If you've got a south-facing (sun-exposed) aspect with a deep snowpack and a rapid spring melt, now there is a higher chance of erosion, loss of nutrients and potential of flooding for downstream communities. The larger and more severe the wildfire, the increased flood potential for valleys."

The research also revealed a 15% increase in snow-water equivalent -- the amount of water contained within the snowpack -- for every 20% increase in tree mortality in the burned areas.

The findings, recently published in Environmental Research Letters, represent the first study to examine the effects of burn severity on snow accumulation and water equivalence using direct measures. The researchers believe the study has considerable implications for water forecasting, especially given that snow-water resources from mountain watersheds provide fresh water for over 20% of the global human population and more than 65% of Utah's water resources.

According to St. Clair, the new data helps paint a more complete picture on water security. To estimate future water resources, he said hydrologists should not only consider topography, aspect (north vs. south facing slopes) and how wet or dry a winter is, they also need to account for the increasing number and severity of wildfires and burn potential to properly assess the risks for flooding and drought.

"Wildfire regimes are changing forest ecosystems, and now we know they're impacting water hydrology too," St. Clair said. "This is our future -- increased fired due to climate change. As a fire ecologist, this research is now in the center of what everyone cares about."

Added Maxwell: "This project was impactful in the scientific community because it shows that not only an increase in the number of fires or in the area they burn, but also the severity of the fire, may have a large effect on the amount and quality of water that's available for us to use. As climate anomalies become more frequent, we have seen and will likely continue to see more severe fires."

Credit: 
Brigham Young University

Ad spending on toddler milks increased four-fold from 2006 to 2015

Hartford, Conn. - Formula companies quadrupled their advertising of toddler milk products over a ten- year period, contributing to a 2.6 times increase in the amount of toddler milk sold, according to a new paper published in Public Health Nutrition from researchers at the Rudd Center for Food Policy & Obesity at the University of Connecticut. This rapid increase in sales occurred despite recommendations from health and nutrition experts. Recently, an expert panel representing the Academy of Nutrition and Dietetics, the American Academy of Pediatric Dentistry, the American Academy of Pediatrics, and the American Heart Association issued guidance recommending that parents do not serve toddler milks, as young children do not need them and the added sugars in these drinks raise concerns.

Toddler milks are a relatively new product category. These milk-based products are typically sold by infant formula manufacturers and marketed as the "next step" for children 12-36 months old who are too old to drink infant formula. Compared to plain whole milk, which is recommended for young toddlers, toddler milks contain added sugars, more sodium, and less protein.

The study, funded by the Robert Wood Johnson Foundation, also found that marketing factors, including lower prices, number of displays in stores, and the cumulative impact of TV advertising spending, were significantly associated with volume of toddler milk sold in a given month and county, for individual brands and the total category. Of note, sales of toddler milks were significantly higher in counties with a higher percentage of college-educated individuals.

"This study shows how well the marketing for toddler milks works," said Yoon-Young Choi, PhD, MS, the study's lead author. "Using a combination of advertising, retail displays, and lower prices, formula manufacturers were able to increase sales of their own toddler milk brands, and at the same time more than double sales for the entire toddler milk category. This marketing appears to have convinced parents that their children need toddler milks, despite expert advice to the contrary."

The study used syndicated market research data to compare total sales of infant formula and toddler milk brands (powder type products) from 2006 to 2015, as well as advertising spending during the same time. The researchers also analyzed the relationship between marketing, including TV advertising spending, displays in stores, and product price, and the amount (in ounces) of toddler milks sold by month and county.

Key findings include:

From 2006 to 2015, annual volume sales of toddler milks increased from 47 to 121 million ounces.

TV advertising spending for toddler milk brands also increased dramatically, from less than $5
million annually in 2006-2008 to more than $20 million annually in 2013-2015.

In contrast, TV advertising for infant formula brands peaked in 2010 at over $60 million and then declined to approximately $5 million in 2015. Infant formula sales also declined by 7% during this time.

In 2014 and 2015, formula companies spent approximately twice as much to advertise toddler milks on TV compared to infant formula.

Companies also reduced the average price per ounce of toddler milk while increasing the average price per ounce of infant formulas.

Previous research from the UConn Rudd Center has shown that the messages used to market toddler milks are also problematic--advertising and package claims imply that they are beneficial for toddlers' nutrition, cognitive development and growth, without substantial evidence that this is true. Toddler milks are also usually stocked next to the infant formula in the store, with similar brand names and packaging as infant formulas offered by the same manufacturers, which can be confusing to parents and caregivers who can't always tell the difference between these product categories and the appropriate product for their child's age.

Study authors call on formula manufacturers to discontinue common misleading marketing practices, such as claims that toddler milks benefit young children's nutrition and development. They also call on healthcare and nutrition professionals to help educate parents about toddler milks, including that these products contain added sugars and that plain whole milk is the best option for young toddlers. In addition, they recommend that the U.S. Food and Drug Administration consider labeling requirements for toddler milks to address consumer confusion about these products.

"With breastfeeding rates in the United States increasing, and demand for infant formula decreasing as a result, it appears formula manufacturers have identified a marketing opportunity to extend their product line to drinks for toddlers," said Jennifer L. Harris, PhD, MBA, a study author and senior research advisor, marketing initiatives at the UConn Rudd Center. "But they should not take advantage of parents' natural concerns about their toddlers' nutrition and development to sell them a product their children don't need, and that could make it more difficult for their children to develop healthy eating habits."

Credit: 
UConn Rudd Center for Food Policy and Obesity

NCRI data shows increase in cancer research funding following five years of growth

New figures from the National Cancer Research Institute (NCRI) show that cancer research funding by NCRI partners has reached £700m for the first time, following five years of increased spending.

Analysis of the NCRI's 18 partner organisations shows that cancer research funders in the UK have increased their collective spend, for the first time spending over £700m in the year 2018/19. This follows five years of spending increases and the highest level of funding since NCRI started collecting data in 2002.

This increase in funding was driven by a 9% increase in spend in Early Detection, Diagnosis and Prognosis research . Research into Treatment and Cancer Control, Survivorship, and Outcomes Research received less funding than in previous years.

The cancers that have some of the worst one- and five-year survival rates in the UK include stomach, oesophageal, lung, brain, liver and pancreatic cancers. Funding for each of these cancers has increased compared to the year 2017/18. Lung cancer now is second only to breast cancer in research spend.

Commenting on these findings, Dr Iain Frame, CEO of NCRI said:

"I am hugely encouraged to see that the trend for increasing cancer research spend continues. At NCRI we are excited about the increase in spend in Early Detection, Diagnosis and Prognosis research and we expect that our Screening, Prevention and Early Diagnosis Group will drive high quality research in this area.

Looking to the future we hope to see the work of the NCRI Living With and Beyond Cancer Group translate into more funding being available in this area, particularly in areas such as palliative and end of life care which currently receives very little funding.

We hope that our partners and the cancer research community can use these data to identify trends and gaps in funding across a range of research areas."

NCRI continues to work with funders of all cancer types to maximise the value and benefits of cancer research for patients and the public. NCRI involves patients, carers and others affected by cancer (also known as 'consumers') at all stages of its activities, including developing clinical trials and high-quality NCRI data studies.

Credit: 
National Cancer Research Institute

'Oldest bamboo' fossil from Eocene Patagonia turns out to be a conifer

image: The holotype of the species Retrophyllum oxyphyllum (comb. nov.), previously thought to be the oldest known bamboo.

Image: 
Peter Wilf

A fossilised leafy branch from the early Eocene in Patagonia described in 1941 is still often cited as the oldest bamboo fossil and the main fossil evidence for a Gondwanan origin of bamboos. However, a recent examination by Dr. Peter Wilf from Pennsylvania State University revealed the real nature of Chusquea oxyphylla. The recent findings, published in the paper in the open-access journal Phytokeys, show that it is actually a conifer.

The corrected identification is significant because the fossil in question was the only bamboo macrofossil still considered from the ancient southern supercontinent of Gondwana. The oldest microfossil evidence for bamboo in the Northern Hemisphere belongs to the Middle Eocene, while other South American fossils are not older than Pliocene.

Over the last decades, some authors have doubted whether the Patagonian fossil was really a bamboo or even a grass species at all. But despite its general significance, modern-day re-examinations of the original specimen were never published. Most scientists referring to it had a chance to study only a photograph found in the original publication from 1941 by the famous Argentine botanists Joaquín Frenguelli and Lorenzo Parodi.

In his recent study of the holotype specimen at Museo de La Plata, Argentina, Dr. Peter Wilf revealed that the fossil does not resemble members of the Chusquea genus or any other bamboo.

"There is no evidence of bamboo-type nodes, sheaths or ligules. Areas that may resemble any bamboo features consist only of the broken departure points of leaf bases diverging from the twig. The decurrent, extensively clasping leaves are quite unlike the characteristically pseudopetiolate leaves of bamboos, and the heterofacially twisted free-leaf bases do not occur in any bamboo or grass," wrote Dr. Wilf.

Instead, Wilf linked the holotype to the recently described fossils of the conifer genus Retrophyllum from the same fossil site, the prolific Laguna del Hunco fossil lake-beds in Chubut Province, Argentina. It matches precisely the distichous fossil foliage form of Retrophyllum spiralifolium, which was described based on a large set of data - a suite of 82 specimens collected from both Laguna del Hunco and the early middle Eocene Río Pichileufú site in Río Negro Province.

Retrophyllum is a genus of six living species of rainforest conifers. Its habitat lies in both the Neotropics and the tropical West Pacific.

The gathered evidence firmly confirms that Chusquea oxyphylla has nothing in common with bamboos. Thus, it requires renaming. Preserving the priority of the older name, Wilf combined Chusquea oxyphylla and Retrophyllum spiralifolium into Retrophyllum oxyphyllum.

The exclusion of a living New World bamboo genus from the overall floral list for Eocene Patagonia weakens the New World biogeographic signal of the late-Gondwanan vegetation of South America, which already showed much stronger links to living floras of the tropical West Pacific.

The strongest New World signal remaining in Eocene Patagonia based on well-described macrofossils comes from fossil fruits of Physalis (a genus of flowering plants including tomatillos and ground cherries), which is an entirely American genus, concludes Dr. Wilf.

Credit: 
Pensoft Publishers