New study links ultra-processed foods and colorectal cancer in men

For many Americans, the convenience of pre-cooked and instant meals may make it easy to overlook the less-than-ideal nutritional information, but a team led by researchers at Tufts University and Harvard University hope that will change after recently discovering a link between the high consumption of ultra-processed foods and an increased risk of colorectal cancer.

In a study published Aug. 31 in The BMJ, researchers found that men who consumed high rates of ultra-processed foods were at 29% higher risk for developing colorectal cancer -- the third most diagnosed cancer in the United States -- than men who consumed much smaller amounts. They did not find the same association in women.

"We started out thinking that colorectal cancer could be the cancer most impacted by diet compared to other cancer types," said Lu Wang, the study's lead author and a postdoctoral fellow at the Friedman School of Nutrition Science and Policy at Tufts. "Processed meats, most of which fall into the category of ultra-processed foods, are a strong risk factor for colorectal cancer. Ultra-processed foods are also high in added sugars and low in fiber, which contribute to weight gain and obesity, and obesity is an established risk factor for colorectal cancer."

The study analyzed responses from over 200,000 participants -- 159,907 women and 46,341 men -- across three large prospective studies which assessed dietary intake and were conducted over more than 25 years. Each participant was provided with a food frequency questionnaire every four years and asked about the frequency of consumption of roughly 130 foods.

For the study in BMJ, participants' intake of ultra-processed foods was then classified into quintiles, ranging in value from the lowest consumption to the highest. Those in the highest quintile were identified as being the most at risk for developing colorectal cancer. Although there was a clear link identified for men, particularly in cases of colorectal cancer in the distal colon, the study did not find an overall increased risk for women who consumed higher amounts of ultra-processed foods.

The Impacts of Ultra-Processed Foods

The analyses revealed differences in the ways that men and women consume ultra-processed foods and the prospective associated cancer risk. Out of the 206,000 participants followed for more than 25 years, the research team documented 1,294 cases of colorectal cancer among men, and 1,922 cases among women.

The team found the strongest association between colorectal cancer and ultra-processed foods among men come from the meat, poultry, or fish-based, ready-to-eat products. "These products include some processed meats like sausages, bacon, ham, and fish cakes. This is consistent with our hypothesis," Wang said.

The team also found higher consumption of sugar-sweetened beverages, like soda, fruit-based beverages, and sugary milk-based beverages, is associated with an increased risk of colorectal cancer in men.

However, not all ultra-processed foods are equally harmful with regard to colorectal cancer risk. "We found an inverse association between ultra-processed dairy foods like yogurt and colorectal cancer risk among women," said co-senior author Fang Fang Zhang, a cancer epidemiologist and interim chair of the Division of Nutrition Epidemiology and Data Science at the Friedman School.

Overall, there was not a link between ultra-processed food consumption and colorectal cancer risk among women. It's possible that the composition of the ultra-processed foods consumed by women could be different than that from men.

"Foods like yogurt can potentially counteract the harmful impacts of other types of ultra-processed foods in women," Zhang said.

Mingyang Song, co-senior author on the study and assistant professor of clinical epidemiology and nutrition at the Harvard T.H. Chan School of Public Health, added that, "Further research will need to determine whether there is a true sex difference in the associations, or if null findings in women in this study were merely due to chance or some other uncontrolled confounding factors in women that mitigated the association."

Although ultra-processed foods are often associated with poor diet quality, there could be factors beyond the poor diet quality of ultra-processed foods that impact the risk of developing colorectal cancer.

The potential role of food additives in altering gut microbiota, promoting inflammation, and contaminants formed during food processing or migrated from food packaging may all promote cancer development, Zhang noted.

Analyzing the Data

With more than a 90% follow-up rate from each of the three studies, the research team had ample data to process and review.

"Cancer takes years or even decades to develop, and from our epidemiological studies, we have shown the potential latency effect -- it takes years to see an effect for certain exposure on cancer risk," said Song. "Because of this lengthy process, it's important to have long-term exposure to data to better evaluate cancer risk."

The studies included:

• The Nurses' Health Study (1986-2014): 121,700 registered female nurses between the ages of 30 and 55
• The Nurses' Health Study II (1991-2015): 116,429 female nurses between the ages of 25 and 42
• The Health Professional Follow-up Study (1986-2014): 51,529 male health professionals between the ages of 40 and 75.

After an exclusionary process for past diagnoses or incomplete surveys, the researchers were left with prospective data from 159,907 women from both NHS studies and 46,341 men.

The team adjusted for potential confounding factors such as race, family history of cancer, history of endoscopy, physical activity hours per week, smoking status, total alcohol intake and total caloric intake, regular aspirin use, and menopausal status.

Zhang is aware that since the participants in these studies all worked in the healthcare field, the findings for this population may not be the same as they would be for the general population, since the participants may be more inclined to eat healthier and lean away from ultra-processed foods. The data may also be skewed because processing has changed over the past two decades.

"But we are comparing within that population those who consume higher amounts versus lower amounts," Zhang reassured. "So those comparisons are valid."

Changing Dietary Patterns

Wang and Zhang previously published a study that identified a trend in increased ultra-processed food consumption in U.S. children and adolescents. Both studies underscore the idea that many different groups of people may be dependent on ultra-processed foods in their daily diets.

"Much of the dependence on these foods can come down to factors like food access and convenience," said Zhang, who is also a member of the Tufts Institute for Global Obesity Research. "Chemically processing foods can aid in extending shelf life, but many processed foods are less healthy than unprocessed alternatives. We need to make consumers aware of the risks associated with consuming unhealthy foods in quantity and make the healthier options easier to choose instead."

Wang knows that change won't happen overnight, and hopes that this study, among others, will contribute to changes in dietary regulations and recommendations.

"Long-term change will require a multi-step approach," Wang added. "Researchers continue to examine how nutrition-related policies, dietary recommendations, and recipe and formula changes, coupled with other healthy lifestyle habits, can improve overall health and reduce cancer burden. It will be important for us to continue to study the link between cancer and diet, as well as the potential interventions to improve outcomes.

Research reported in this article was supported by awards from the National Institutes of Health's National Institute on Minority Health and Health Disparities (R01MD011501), National Cancer Institute (UM1CA186107; P01CA087969; U01CA176726; U01CA167552; and R00CA215314), and a Mentored Research Scholar Grant in Applied and Clinical Research from the American Cancer Society. The content is solely the authors' responsibility and does not necessarily represent the official views of the National Institutes of Health.

Journal Reference:

1. Lu Wang, Mengxi Du, Kai Wang, Neha Khandpur, Sinara Laurini Rossato, Jean-Philippe Drouin-Chartier, Euridice Martínez Steele, Edward Giovannucci, Mingyang Song, Fang Fang Zhang. Association of ultra-processed food consumption with colorectal cancer risk among men and women: results from three prospective US cohort studies. BMJ, 2022; e068921 DOI: 10.1136/bmj-2021-068921 

Courtesy:

Tufts University, Health Sciences Campus. "New study links ultra-processed foods and colorectal cancer in men: Researchers found that men who consumed high rates of ultra-processed foods were at higher risk for developing colorectal cancer than those who did not." ScienceDaily. ScienceDaily, 31 August 2022. <www.sciencedaily.com/releases/2022/08/220831210024.htm>.

 

Artificial photosynthesis can produce food without sunshine

Scientists have found a way to bypass the need for biological photosynthesis altogether and create food independent of sunlight by using artificial photosynthesis. The technology uses a two-step electrocatalytic process to convert carbon dioxide, electricity, and water into acetate. Food-producing organisms then consume acetate in the dark to grow. The hybrid organic-inorganic system could increase the conversion efficiency of sunlight into food, up to 18 times more efficient for some foods.

Photosynthesis has evolved in plants for millions of years to turn water, carbon dioxide, and the energy from sunlight into plant biomass and the foods we eat. This process, however, is very inefficient, with only about 1% of the energy found in sunlight ending up in the plant. Scientists at UC Riverside and the University of Delaware have found a way to bypass the need for biological photosynthesis altogether and create food independent of sunlight by using artificial photosynthesis.

The research, published in Nature Food, uses a two-step electrocatalytic process to convert carbon dioxide, electricity, and water into acetate, the form of the main component of vinegar. Food-producing organisms then consume acetate in the dark to grow. Combined with solar panels to generate the electricity to power the electrocatalysis, this hybrid organic-inorganic system could increase the conversion efficiency of sunlight into food, up to 18 times more efficient for some foods.

"With our approach we sought to identify a new way of producing food that could break through the limits normally imposed by biological photosynthesis," said corresponding author Robert Jinkerson, a UC Riverside assistant professor of chemical and environmental engineering.

In order to integrate all the components of the system together, the output of the electrolyzer was optimized to support the growth of food-producing organisms. Electrolyzers are devices that use electricity to convert raw materials like carbon dioxide into useful molecules and products. The amount of acetate produced was increased while the amount of salt used was decreased, resulting in the highest levels of acetate ever produced in an electrolyzer to date.

"Using a state-of-the-art two-step tandem CO₂ electrolysis setup developed in our laboratory, we were able to achieve a high selectivity towards acetate that cannot be accessed through conventional CO₂ electrolysis routes," said corresponding author Feng Jiao at University of Delaware.

Experiments showed that a wide range of food-producing organisms can be grown in the dark directly on the acetate-rich electrolyzer output, including green algae, yeast, and fungal mycelium that produce mushrooms. Producing algae with this technology is approximately fourfold more energy efficient than growing it photosynthetically. Yeast production is about 18-fold more energy efficient than how it is typically cultivated using sugar extracted from corn.

"We were able to grow food-producing organisms without any contributions from biological photosynthesis. Typically, these organisms are cultivated on sugars derived from plants or inputs derived from petroleum -- which is a product of biological photosynthesis that took place millions of years ago. This technology is a more efficient method of turning solar energy into food, as compared to food production that relies on biological photosynthesis," said Elizabeth Hann, a doctoral candidate in the Jinkerson Lab and co-lead author of the study.

The potential for employing this technology to grow crop plants was also investigated. Cowpea, tomato, tobacco, rice, canola, and green pea were all able to utilize carbon from acetate when cultivated in the dark.

"We found that a wide range of crops could take the acetate we provided and build it into the major molecular building blocks an organism needs to grow and thrive. With some breeding and engineering that we are currently working on we might be able to grow crops with acetate as an extra energy source to boost crop yields," said Marcus Harland-Dunaway, a doctoral candidate in the Jinkerson Lab and co-lead author of the study.

By liberating agriculture from complete dependence on the sun, artificial photosynthesis opens the door to countless possibilities for growing food under the increasingly difficult conditions imposed by anthropogenic climate change. Drought, floods, and reduced land availability would be less of a threat to global food security if crops for humans and animals grew in less resource-intensive, controlled environments. Crops could also be grown in cities and other areas currently unsuitable for agriculture, and even provide food for future space explorers.

"Using artificial photosynthesis approaches to produce food could be a paradigm shift for how we feed people. By increasing the efficiency of food production, less land is needed, lessening the impact agriculture has on the environment. And for agriculture in non-traditional environments, like outer space, the increased energy efficiency could help feed more crew members with less inputs," said Jinkerson.

This approach to food production was submitted to NASA's Deep Space Food Challenge where it was a Phase I winner. The Deep Space Food Challenge is an international competition where prizes are awarded to teams to create novel and game-changing food technologies that require minimal inputs and maximize safe, nutritious, and palatable food outputs for long-duration space missions.

"Imagine someday giant vessels growing tomato plants in the dark and on Mars -- how much easier would that be for future Martians?" said co-author Martha Orozco-Cárdenas, director of the UC Riverside Plant Transformation Research Center.

Andres Narvaez, Dang Le, and Sean Overa also contributed to the research.

The research was supported by the Translational Research Institute for Space Health (TRISH) through NASA (NNX16AO69A), Foundation for Food and Agriculture Research (FFAR), the Link Foundation, the U.S. National Science Foundation, and the U.S. Department of Energy. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the Foundation for Food and Agriculture Research.

Journal Reference:

1. Elizabeth C. Hann, Sean Overa, Marcus Harland-Dunaway, Andrés F. Narvaez, Dang N. Le, Martha L. Orozco-Cárdenas, Feng Jiao, Robert E. Jinkerson. A hybrid inorganic–biological artificial photosynthesis system for energy-efficient food production. Nature Food, 2022; 3 (6): 461 DOI: 10.1038/s43016-022-00530-x 

Courtesy:

University of California - Riverside. "Artificial photosynthesis can produce food without sunshine." ScienceDaily. ScienceDaily, 23 June 2022. <www.sciencedaily.com/releases/2022/06/220623122624.htm>.

 

Scientists develop a new non-opioid pain killer with fewer side effects

A promising new non-opioid painkiller (analgesic) with potentially fewer side effects compared to other potent painkillers, has been discovered.

A team of scientists, co-led by researchers from the School of Life Sciences, University of Warwick, has investigated a compound called BnOCPA (benzyloxy-cyclopentyladenosine), found to be a potent and selective analgesic which is non-addictive in test model systems. BnOCPA also has a unique mode of action and potentially opens a new pipeline for the development of new analgesic drugs.

The research by the team at Warwick, together with colleagues at the University of Cambridge, University of Bern, Monash University, Coventry University and industrial collaborators, is published in Nature Communications in a paper entitled "Selective activation of G?ob by an adenosine A1 receptor agonist elicits analgesia without cardiorespiratory depression."

In the UK between one third and one half of the population report moderately to severely disabling chronic pain. Such pain has a negative impact on quality of life and many of the commonly used pain killers produce side effects. Opioid drugs, such as morphine and oxycodone, can lead to addiction and are dangerous in overdose. There is therefore an unmet need for new and potent pain killing drugs.

Many drugs act via proteins on the surface of cell surfaces that activate adapter molecules called G proteins. The activation of G proteins can lead to many cellular effects. BnOCPA is unique in that it only activates one type of G protein, leading to very selective effects and thus reducing potential side effects.

Dr Mark Wall, from the School of Life Sciences at the University of Warwick, who led the research said: "The selectivity and potency of BnOCPA make it truly unique and we hope that with further research it will be possible to generate potent painkillers to help patients cope with chronic pain."

Professor Bruno Frenguelli, principal investigator on the project, from the University of Warwick's School of Life Sciences, said: "This is a fantastic example of serendipity in science. We had no expectations that BnOCPA would behave any differently from other molecules in its class, but the more we looked into BnOCPA we discovered properties that had never been seen before, and which may open up new areas of medicinal chemistry."

Professor Graham Ladds, co-principal investigator on the project, from the University of Cambridge, said: "This is an amazing story looking at agonist bias for a GPCR. Not only does BnOCPA have the potential to be a new type of painkiller, but it has shown us a new method for targeting other GPCRs in drug discovery."

Journal Reference:

1. Mark J. Wall, Emily Hill, Robert Huckstepp, Kerry Barkan, Giuseppe Deganutti, Michele Leuenberger, Barbara Preti, Ian Winfield, Sabrina Carvalho, Anna Suchankova, Haifeng Wei, Dewi Safitri, Xianglin Huang, Wendy Imlach, Circe La Mache, Eve Dean, Cherise Hume, Stephanie Hayward, Jess Oliver, Fei-Yue Zhao, David Spanswick, Christopher A. Reynolds, Martin Lochner, Graham Ladds, Bruno G. Frenguelli. Selective activation of Gαob by an adenosine A1 receptor agonist elicits analgesia without cardiorespiratory depression. Nature Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-31652-2 

Courtesy:

University of Warwick. "Scientists develop a new non-opioid pain killer with fewer side effects." ScienceDaily. ScienceDaily, 20 July 2022. <www.sciencedaily.com/releases/2022/07/220720102521.htm>.

 

 

People generate their own oxidation field and change the indoor air chemistry around them

People typically spend 90 percent of their lives inside, at home, at work, or in transport. Within these enclosed spaces, occupants are exposed to a multitude of chemicals from various sources, including outdoor pollutants penetrating indoors, gaseous emissions from building materials and furnishings, and products of our own activities such as cooking and cleaning. In addition, we are ourselves potent mobile emission sources of chemicals that enter the indoor air from our breath and skin.

But how do the chemicals disappear again? In the atmosphere outdoors, this happens to a certain extent naturally by itself, when it rains and through chemical oxidation. Hydroxyl (OH) radicals are largely responsible for this chemical cleaning. These very reactive molecules are also called the detergents of the atmosphere and they are primarily formed when UV light from the sun interacts with ozone and water vapor.

Indoors, on the other hand, the air is of course far less affected by direct sunlight and rain. Since UV rays are largely filtered out by glass windows it has been generally assumed that the concentration of OH radicals is substantially lower indoors than outdoors and that ozone, leaking in from outdoors, is the major oxidant of indoor airborne chemical pollutants.

OH radicals are formed from ozone and skin oils

However, now it has been discovered that high levels of OH radicals can be generated indoors, simply due to the presence of people and ozone. This has been shown by a team led by the Max Planck Institute for Chemistry in cooperation with researchers from the USA and Denmark.

"The discovery that we humans are not only a source of reactive chemicals, but we are also able to transform these chemicals ourselves was very surprising to us," says Nora Zannoni, first author of the study published in the research magazine Science, and now at the Institute of Atmospheric Sciences and Climate in Bologna, Italy. "The strength and shape of the oxidation field are determined by how much ozone is present, where it infiltrates, and how the ventilation of the indoor space is configured," adds the scientist from Jonathan Williams' team. The levels the scientists found were even comparable to outside daytime OH concentrations levels.

The oxidation field is generated by the reaction of ozone with oils and fats on our skin, especially the unsaturated triterpene squalene, which constitutes about 10 percent of the skin lipids that protect our skin and keep it supple. The reaction releases a host of gas phase chemicals containing double bonds that react further in the air with ozone to generate substantial levels of OH radicals. These squalene degradation products were characterized and quantified individually using Proton Transfer reaction Mass Spectrometry and fast gas chromatograph-mass spectrometry systems. In addition, the total OH reactivity was determined in parallel enabling the OH levels to be quantified empirically.

The experiments were conducted at the Technical University of Denmark (DTU) in Copenhagen. Four test subjects stayed in a special climate-controlled chamber under standardized conditions. Ozone was added to the chamber air inflow in a quantity that was not harmful to humans but representative of higher indoor levels. The team determined the OH values before and during the volunteers' stay both with and without ozone present.

In order to understand how the human-generated OH field looked like in space and time during the experiments, results from a detailed multiphase chemical kinetic model from the University of California, Irvine were combined with a computational fluid dynamics model from Pennsylvania State University, both based in the USA. After validating the models against the experimental results, the modeling team examined how the human-generated OH field varied under different conditions of ventilation and ozone, beyond those tested in the laboratory. From the results, it was clear that the OH radicals were present, abundant, and forming strong spatial gradients.

"Our modeling team is the first and currently the only group that can integrate chemical processes between the skin and indoor air, from molecular scales to room scales," said Manabu Shiraiwa, a professor at UC Irvine who led the modeling part of the new work. "The model makes sense of the measurements -- why OH is generated from the reaction with the skin."

Shiraiwa added that there remain unanswered questions, like the way humidity levels impact the reactions the team traced. "I think this study opens up a new avenue for indoor air research," he said.

Adapt test methods for furniture and building materials

"We need to rethink indoor chemistry in occupied spaces because the oxidation field we create will transform many of the chemicals in our immediate vicinity. OH can oxidize many more species than ozone, creating a multitude of products directly in our breathing zone with as yet unknown health impacts." This oxidation field will also impact the chemical signals we emit and receive," says project leader Jonathan Williams, "and possibly help explain the recent finding that our sense of smell is generally more sensitive to molecules that react faster with OH."

The new finding also has implications for our health: Currently, chemical emissions of many materials and furnishings are being tested in isolation before they are approved for sale. However, it would be advisable to also conduct tests in the presence of people and ozone, says atmospheric chemist Williams. This is because oxidation processes can lead to the generation of respiratory irritants such as 4-oxopentanal (4-OPA) and other OH radical-generated oxygenated species, and small particles in the immediate vicinity of the respiratory tract. These can have adverse effects, especially in children and the infirm.

These findings are part of the project ICHEAR (Indoor Chemical Human Emissions and Reactivity Project) which brought together a group of collaborating international scientists from Denmark (DTU), the USA (Rutgers University), and Germany (MPI). The modeling was part of the MOCCIE project based at the University of California Irvine and the Pennsylvania State University. Both projects were funded by grants from the A. P. Sloan foundation.

Journal Reference:

1. Nora Zannoni, Pascale S. J. Lakey, Youngbo Won, Manabu Shiraiwa, Donghyun Rim, Charles J. Weschler, Nijing Wang, Lisa Ernle, Mengze Li, Gabriel Bekö, Pawel Wargocki, Jonathan Williams. The human oxidation field. Science, 2022; 377 (6610): 1071 DOI: 10.1126/science.abn0340 

Courtesy:

Max Planck Institute for Chemistry. "People generate their own oxidation field and change the indoor air chemistry around them." ScienceDaily. ScienceDaily, 1 September 2022. <www.sciencedaily.com/releases/2022/09/220901151703.htm>.

 

 

Brains cells born together wire and fire together for life

Brain cells with the same "birthdate" are more likely to wire together into cooperative signaling circuits that carry out many functions, including the storage of memories, a new study finds.

Led by researchers from NYU Grossman School of Medicine, the new study on the brains of mice developing in the womb found that brain cells (neurons) with the same birthdate showed distinct connectivity and activity throughout the animals' adult lives, whether they were asleep or awake.

Published online August 22 in Nature Neuroscience, the findings suggest that evolution took advantage of the orderly birth of neurons -- by gestational day -- to form localized microcircuits in the hippocampus, the brain region that forms memories. Rather than attempting to create each new memory from scratch, the researchers suggest, the brain may exploit the stepwise formation of neuronal layers to establish neural templates, like "Lego pieces," that match each new experience to an existing template as it is remembered.

These rules of circuit assembly would suggest that cells born together are more likely to encode memories together, and to fail together, potentially implicating neuronal birthdate in diseases like autism and Alzheimer's, say the authors. With changes to the number of cells born at different days, the developing brain may be more vulnerable on some gestational days to viral infections, toxins, or alcohol.

"Our study's results suggest that which day a hippocampal neuron is born strongly influences both how that single cell performs, and how populations of such cells signal together throughout life," says senior study author György Buzsáki, MD, PhD, the Biggs Professor in the Department of Neuroscience and Physiology at NYU Langone Health. "This work may reshape how we study neurodevelopmental disorders, which have traditionally been looked at through a molecular or genetic, rather than a developmental, lens," says Buzsáki, also a faculty member in the Neuroscience Institute at NYU Langone."

New Understanding

The current study's innovation rests on tracking the activity of neurons of a given birthdate into adulthood. To accomplish this, the researchers relied on a technique that allowed them to transfer DNA into cells that were undergoing division into neurons in the womb. The DNA expressed markers that tagged brain cells that were born on same day, akin to a barcode. This labeling method then enabled the researchers to study these neurons in the adult animal.

Using a combination of techniques, the new study found that neurons of the same birthdate tend to "co-fire" together, characterized by synchronized swings in their positive and negative charges, allowing them to transmit electrical signals collectively. A likely reason for the co-firing, say the authors, is that neurons with the same birthdate are connected via shared neurons.

Past work had shown that activity in the hippocampus can be described in terms patterns of collective neuronal activity during waking and sleep. During sleep, for instance, when each day's memories are consolidated for long-term memory storage, hippocampal neurons engage in a cyclical burst of activity called the "sharp wave-ripple," named for the shape it takes when captured graphically by EEG, a technology that records brain activity with electrodes.

"Our results show that neurons born on the same day become part of the same cooperating assemblies, and participate in the same sharp wave-ripples and represent the same memories," says first author Roman Huszár, a graduate student in Buzsáki's lab. "These relationships, and the pre-set templates they encode, have a key implication for hippocampal function: the storage of a memory about a place or event."

Moving forward, the team plans additional experiments to identify the genes active in the same birthdate neurons in different brain regions, and to test their role in memory formation and behavior.

Along with Buzsáki and and Huszár, the other study authors were Yunchang Zhang from the NYU Neuroscience Institute and the Center for Neural Science at New York University; and Heike Blockus of the Department of Neuroscience and Zuckerman Mind Brain Behavior Institute at Columbia University. Funding for the study was provide by National Institutes of Health grants RO1 MH122391 and U19 NS107616.

Journal Reference:

1. Roman Huszár, Yunchang Zhang, Heike Blockus, György Buzsáki. Preconfigured dynamics in the hippocampus are guided by embryonic birthdate and rate of neurogenesis. Nature Neuroscience, 2022; DOI: 10.1038/s41593-022-01138-x 

Courtesy:

NYU Langone Health / NYU Grossman School of Medicine. "Brains cells born together wire and fire together for life." ScienceDaily. ScienceDaily, 22 August 2022. <www.sciencedaily.com/releases/2022/08/220822130226.htm>.

Team developing oral insulin tablet sees breakthrough results

A team of University of British Columbia researchers working on developing oral insulin tablets as a replacement for daily insulin injections have made a game-changing discovery.

Researchers have discovered that insulin from the latest version of their oral tablets is absorbed by rats in the same way that injected insulin is.

"These exciting results show that we are on the right track in developing an insulin formulation that will no longer need to be injected before every meal, improving the quality of life, as well as mental health, of more than nine million Type 1 diabetics around the world." says professor Dr. Anubhav Pratap-Singh (he/him), the principal investigator from the faculty of land and food systems.

He explains the inspiration behind the search for a non-injectable insulin comes from his diabetic father who has been injecting insulin 3-4 times a day for the past 15 years.

According to Dr. Alberto Baldelli (he/him), a senior fellow in Dr. Pratap-Singh's lab, they are now seeing nearly 100 per cent of the insulin from their tablets go straight into the liver. In previous attempts to develop a drinkable insulin, most of the insulin would accumulate in the stomach.

"Even after two hours of delivery, we did not find any insulin in the stomachs of the rats we tested. It was all in the liver and this is the ideal target for insulin -- it's really what we wanted to see," says Yigong Guo (he/him), first author of the study and a PhD candidate working closely on the project.

Changing the mode of delivery

When it comes to insulin delivery, injections are not the most comfortable or convenient for diabetes patients. But with several other oral insulin alternatives also being tested and developed, the UBC team worked to solve where and how to facilitate a higher absorption rate.

Dr. Pratap-Singh's team developed a different kind of tablet that isn't made for swallowing, but instead dissolves when placed between the gum and cheek.

This method makes use of the thin membrane found within the lining of the inner cheek and back of the lips (also known as the buccal mucosa). It delivered all the insulin to the liver without wasting or decomposing any insulin along the way.

"For injected insulin we usually need 100iu per shot. Other swallowed tablets being developed that go to the stomach might need 500iu of insulin, which is mostly wasted, and that's a major problem we have been trying to work around," Yigong says.

Most swallowed insulin tablets in development tend to release insulin slowly over two to four hours, while fast-release injected insulin can be fully released in 30-120 minutes.

"Similar to the rapid-acting insulin injection, our oral delivery tablet absorbs after half an hour and can last for about two to four hours long," says Dr. Baldelli.

Potential broad benefits

The study is yet to go into human trials, and for this to happen Dr. Pratap-Singh says they will require more time, funding and collaborators. But beyond the clear potential benefits to diabetics, he says the tablet they are developing could also be more sustainable, cost-effective and accessible.

"More than 300,000 Canadians have to inject insulin multiple times per day," Dr. Pratap-Singh says. "That is a lot of environmental waste from the needles and plastic from the syringe that might not be recycled and go to landfill, which wouldn't be a problem with an oral tablet."

He explains that their hope is to reduce the cost of insulin per dose since their oral alternative could be cheaper and easier to make. Transporting the tablets would be easier for diabetics, who currently have to think about keeping their doses cool.

Journal Reference:

1. Yigong Guo, Alberto Baldelli, Anika Singh, Farahnaz Fathordoobady, David Kitts, Anubhav Pratap-Singh. Production of high loading insulin nanoparticles suitable for oral delivery by spray drying and freeze drying techniques. Scientific Reports, 2022; 12 (1) DOI: 10.1038/s41598-022-13092-6 

Courtesy:

University of British Columbia. "Team developing oral insulin tablet sees breakthrough results." ScienceDaily. ScienceDaily, 30 August 2022. <www.sciencedaily.com/releases/2022/08/220830093215.htm>.

 

Mosquitoes have neuronal fail-safes to make sure they can always smell humans

When female mosquitoes are looking for a human to bite, they smell a unique cocktail of body odors that we emit into the air. These odors then stimulate receptors in the mosquitoes' antenna. Scientists have tried deleting these receptors in attempts to make humans undetectable to mosquitoes.

However, even after knocking out an entire family of odor-sensing receptors from the mosquito genome, mosquitoes still find a way to bite us. Now, a group of researchers, publishing in the journal Cell on August 18, found that mosquitoes have evolved redundant fail-safes in their olfactory system that make sure they can always smell our scents.

"Mosquitoes are breaking all of our favorite rules of how animals smell things," says Margo Herre, a scientist at Rockefeller University and one of the lead authors of the paper.

In most animals, an olfactory neuron is only responsible for detecting one type of odor. "If you're a human and you lose a single odorant receptor, all of the neurons that express that receptor will lose the ability to smell that smell," says Leslie Vosshall of the Howard Hughes Medical Institute and a professor at Rockefeller University and the senior author of the paper. But she and her colleagues found that this is not the case in mosquitoes.

"You need to work harder to break mosquitoes because getting rid of a single receptor has no effect," says Vosshall. "Any future attempts to control mosquitoes by repellents or anything else has to take into account how unbreakable their attraction is to us."

"This project really started unexpectedly when we were looking at how human odor was encoded in the mosquito brain," says Meg Younger, a professor at Boston University and one of the lead authors of the paper.

They found that neurons stimulated by the human odor 1-octen-3-ol are also stimulated by amines, another type of chemical mosquitoes use to look for humans. This is unusual since according to all existing rules of how animals smell, neurons encode odor with narrow specificity, suggesting that 1-octen-3-ol neurons should not detect amines.

"Surprisingly, the neurons for detecting humans through 1-octen-3-ol and amine receptors were not separate populations," says Younger. This may allow all human-related odors to activate "the human-detecting part" of the mosquito brain even if some of the receptors are lost, acting as a fail-safe.

The team also utilized single-nucleus RNA sequencing to see what other receptors individual mosquito olfactory neurons are expressing. "The result gave us a broad view of just how common co-expression of receptors is in mosquitoes," says Olivia Goldman, another lead author of the paper.

Vosshall thinks that other insects may have a similar mechanism. Christopher Potter's research group at Johns Hopkins University recently reported that fruit flies have similar co-expression of receptors in their neurons. "This may be a general strategy for insects that depend heavily on their sense of smell," says Vosshall.

In the future, Meg Younger's group plans to uncover the functional significance of the co-expression of different types of olfactory receptors.

This work was partially supported by the U.S. National Institute of Health.

Journal Reference:

1. Margaret Herre, Olivia V. Goldman, Tzu-Chiao Lu, Gabriela Caballero-Vidal, Yanyan Qi, Zachary N. Gilbert, Zhongyan Gong, Takeshi Morita, Saher Rahiel, Majid Ghaninia, Rickard Ignell, Benjamin J. Matthews, Hongjie Li, Leslie B. Vosshall, Meg A. Younger. Non-canonical odor coding in the mosquito. Cell, 2022; 185 (17): 3104 DOI: 10.1016/j.cell.2022.07.024 

Courtesy:

Cell Press. "Mosquitoes have neuronal fail-safes to make sure they can always smell humans." ScienceDaily. ScienceDaily, 18 August 2022. <www.sciencedaily.com/releases/2022/08/220818122351.htm>.

 

People with similar faces likely have similar DNA, study finds

 A collection of photos of genetically unrelated lookalikes, along with DNA analysis, revealed that strong facial similarity is associated with shared genetic variants. The work appears August 23 in the journal Cell Reports.

"Our study provides a rare insight into human likeness by showing that people with extreme lookalike faces share common genotypes, whereas they are discordant at the epigenome and microbiome levels," says senior author Manel Esteller of the Josep Carreras Leukaemia Research Institute in Barcelona, Spain. "Genomics clusters them together, and the rest sets them apart."

The number of people identified online as virtual twins or doubles who are genetically unrelated has increased due to the expansion of the World Wide Web and the possibility of exchanging pictures of humans across the planet. In the new study, Esteller and his team set out to characterize, on a molecular level, random human beings that objectively share facial features.

To do so, they recruited human doubles from the photographic work of François Brunelle, a Canadian artist who has been obtaining worldwide pictures of lookalikes since 1999. They obtained headshot pictures of 32 lookalike couples. The researchers determined an objective measure of likeness for the pairs using three different facial recognition algorithms.

In addition, the participants completed a comprehensive biometric and lifestyle questionnaire and provided saliva DNA for multiomics analysis. "This unique set of samples has allowed us to study how genomics, epigenomics, and microbiomics can contribute to human resemblance," Esteller says.

Overall, the results revealed that these individuals share similar genotypes, but differ in their DNA methylation and microbiome landscapes. Half of the lookalike pairs were clustered together by all three algorithms. Genetic analysis revealed that 9 of these 16 pairs clustered together, based on 19,277 common single-nucleotide polymorphisms.

Moreover, physical traits such as weight and height, as well as behavioral traits such as smoking and education, were correlated in lookalike pairs. Taken together, the results suggest that shared genetic variation not only relates to similar physical appearance, but may also influence common habits and behavior.

"We provided a unique insight into the molecular characteristics that potentially influence the construction of the human face," Esteller says. "We suggest that these same determinants correlate with both physical and behavioral attributes that constitute human beings."

A few study limitations include the small sample size, the use of 2D black-and-white images, and the predominance of European participants. Despite these caveats, the findings may provide a molecular basis for future applications in various fields such as biomedicine, evolution, and forensics.

"These results will have future implications in forensic medicine -- reconstructing the criminal's face from DNA -- and in genetic diagnosis -- the photo of the patient's face will already give you clues as to which genome he or she has," Esteller says. "Through collaborative efforts, the ultimate challenge would be to predict the human face structure based on the individual's multiomics landscape."

This work was funded by the governments of Catalonia and Spain, as well as the Cellex Foundation.

Journal Reference:

1. Ricky S. Joshi, Maria Rigau, Carlos A. García-Prieto, Manuel Castro de Moura, David Piñeyro, Sebastian Moran, Veronica Davalos, Pablo Carrión, Manuel Ferrando-Bernal, Iñigo Olalde, Carles Lalueza-Fox, Arcadi Navarro, Carles Fernández-Tena, Decky Aspandi, Federico M. Sukno, Xavier Binefa, Alfonso Valencia, Manel Esteller. Look-alike humans identified by facial recognition algorithms show genetic similarities. Cell Reports, 2022; 40 (8): 111257 DOI: 10.1016/j.celrep.2022.111257 

Courtesy:

Cell Press. "People with similar faces likely have similar DNA, study finds." ScienceDaily. ScienceDaily, 23 August 2022. <www.sciencedaily.com/releases/2022/08/220823115609.htm>.

 

 

Gene therapy partly restores cone function in two completely colorblind children

Gene therapy has partly restored the function of the retina's cone receptors in two children who were born completely colourblind, reports a new study led by UCL researchers.

The findings, published in Brain, provide hope that the treatment is effectively activating previously dormant communication pathways between the retina and the brain, drawing on the plastic nature of the developing adolescent brain.

The academically-led study has been running alongside a phase 1/2 clinical trial in children with achromatopsia, using a new way to test whether the treatment is changing the neural pathways specific to the cones.

Achromatopsia is caused by disease-causing variants to one of a few genes. It affects cone cells, which (along with rods) are one of two types of photoreceptors in the eyes. As cones are responsible for colour vision, people with achromatopsia are completely colourblind, while they also have very poor vision overall and find bright light uncomfortable (photophobia). Their cone cells do not send signals to the brain, but many remain present, so researchers have been seeking to activate the dormant cells.

Lead author Dr Tessa Dekker (UCL Institute of Ophthalmology) said: "Our study is the first to directly confirm widespread speculation that gene therapy offered to children and adolescents can successfully activate the dormant cone photoreceptor pathways and evoke visual signals never previously experienced by these patients.

"We are demonstrating the potential of leveraging the plasticity of our brains, which may be particularly able to adapt to treatment effects when people are young."

The study involved four young people with achromatopsia aged 10 to 15 years old, who were taking part in two trials led by Professor James Bainbridge at UCL and Moorfields Eye Hospital, sponsored by MeiraGTx-Janssen Pharmaceuticals.

The two trials are testing gene therapies targeting specific genes known to be implicated in achromatopsia (the two trials are each targeting a different gene). Their primary aim is to test that the treatment is safe, while also testing for improved vision. Their results have not yet been fully compiled so the overall effectiveness of the treatments remains to be determined.

The accompanying academic study used a novel functional magnetic resonance imaging (fMRI, a type of brain scan) mapping approach to separate emerging post-treatment cone signals from existing rod-driven signals in patients, allowing the researchers to pinpoint any changes in visual function, after treatment, directly to the targeted cone photoreceptor system. They employed a 'silent substitution' technique using pairs of lights to selectively stimulate cones or rods. The researchers also had to adapt their methods to accommodate nystagmus (involuntary eye oscillations, or 'dancing eyes'), another symptom of achromatopsia. The results were compared to tests involving nine untreated patients and 28 volunteers with normal vision.

Each of the four children was treated with gene therapy in one eye, enabling doctors to compare the treatment's effectiveness with the untreated eye.

For two of the four children, there was strong evidence for cone-mediated signals in the brain's visual cortex coming from the treated eye, six to 14 months after treatment. Before the treatment, the patients showed no evidence of cone function on any tests. After treatment, their measures closely resembled those from normal sighted study participants.

The study participants also completed a psychophysical test of cone function, which assesses the ability of the eyes to distinguish between different levels of contrast. This showed there was a difference in cone-supported vision in the treated eyes in the same two children.

The researchers say they cannot confirm whether the treatment was ineffective in the other two study participants, or if there may have been treatment effects that were not picked up by the tests they used, or if effects are delayed.

Co-lead author Dr Michel Michaelides (UCL Institute of Ophthalmology and Moorfields Eye Hospital), who is also co-investigator on both clinical trials, said: "In our trials, we are testing whether providing gene therapy early in life may be most effective while the neural circuits are still developing. Our findings demonstrate unprecedented neural plasticity, offering hope that treatments could enable visual functions using signalling pathways that have been dormant for years.

"We are still analysing the results from our two clinical trials, to see whether this gene therapy can effectively improve everyday vision for people with achromatopsia. We hope that with positive results, and with further clinical trials, we could greatly improve the sight of people with inherited retinal diseases."

Dr Dekker added: "We believe that incorporating these new tests into future clinical trials could accelerate the testing of ocular gene therapies for a range of conditions, by offering unparalleled sensitivity to treatment effects on neural processing, while also providing new and detailed insight into when and why these therapies work best."

One of the study participants commented: "Seeing changes to my vision has been very exciting, so I'm keen to see if there are any more changes and where this treatment as a whole might lead in the future.

"It's actually quite difficult to imagine what or just how many impacts a big improvement in my vision could have, since I've grown up with and become accustomed to low vision, and have adapted and overcome challenges (with a lot of support from those around me) throughout my life."

The study was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, the Economic & Social Research Council, MeiraGTx, Retina UK, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, Foundation Fighting Blindness, Wellcome, Ardalan Family Scholarship, the Persia Educational Foundation Maryam Mirzakhani Scholarship, and the Sir Richard Stapley Educational Trust.

Journal Reference:

1. Mahtab Farahbakhsh, Elaine J Anderson, Roni O Maimon-Mor, Andy Rider, John A Greenwood, Nashila Hirji, Serena Zaman, Pete R Jones, D Samuel Schwarzkopf, Geraint Rees, Michel Michaelides, Tessa M Dekker. A demonstration of cone function plasticity after gene therapy in achromatopsia. Brain, 2022; DOI: 10.1093/brain/awac226

 Courtesy:

University College London. "Gene therapy partly restores cone function in two completely colorblind children." ScienceDaily. ScienceDaily, 24 August 2022. <www.sciencedaily.com/releases/2022/08/220824102951.htm>.

The bacteria powering a truly green revolution in personal electronics

Researchers at the University of Massachusetts Amherst recently announced that they have figured out how to engineer a biofilm that harvests the energy in evaporation and converts it to electricity. This biofilm, which was announced in Nature Communications, has the potential to revolutionize the world of wearable electronics, powering everything from personal medical sensors to personal electronics.

"This is a very exciting technology," says Xiaomeng Liu, graduate student in electrical and computer engineering in UMass Amherst's College of Engineering and the paper's lead author. "It is real green energy, and unlike other so-called 'green-energy' sources, its production is totally green."

That's because this biofilm -- a thin sheet of bacterial cells about the thickness of a sheet of paper -- is produced naturally by an engineered version of the bacteria Geobacter sulfurreducens. G. sulfurreducens is known to produce electricity and has been used previously in "microbial batteries" to power electrical devices. But such batteries require that G. sulfurreducens is properly cared for and fed a constant diet. By contrast, this new biofilm, which can supply as much, if not more, energy than a comparably sized battery, works, and works continuously, because it is dead. And because it's dead, it doesn't need to be fed.

"It's much more efficient," says Derek Lovley, Distinguished Professor of Microbiology at UMass Amherst and one of the paper's senior authors. "We've simplified the process of generating electricity by radically cutting back on the amount of processing needed. We sustainably grow the cells in a biofilm, and then use that agglomeration of cells. This cuts the energy inputs, makes everything simpler and widens the potential applications."

The secret behind this new biofilm is that it makes energy from the moisture on your skin. Though we daily read stories about solar power, at least 50% of the solar energy reaching the earth goes toward evaporating water. "This is a huge, untapped source of energy," says Jun Yao, professor of electrical and computer engineering at UMass, and the paper's other senior author. Since the surface of our skin is constantly moist with sweat, the biofilm can "plug-in" and convert the energy locked in evaporation into enough energy to power small devices.

"The limiting factor of wearable electronics," says Yao, "has always been the power supply. Batteries run down and have to be changed or charged. They are also bulky, heavy, and uncomfortable." But a clear, small, thin flexible biofilm that produces a continuous and steady supply of electricity and which can be worn, like a Band-Aid, as a patch applied directly to the skin, solves all these problems.

What makes this all work is that G. sulfurreducens grows in colonies that look like thin mats, and each of the individual microbes connects to its neighbors through a series of natural nanowires. The team then harvests these mats and uses a laser to etch small circuits into the films. Once the films are etched, they're sandwiched between electrodes and finally sealed in a soft, sticky, breathable polymer that you can apply directly to your skin. Once this tiny battery is "plugged in" by applying it to your body, it can power small devices.

"Our next step is to increase the size of our films to power more sophisticated skin-wearable electronics," says Yao, and Liu points out that one of the goals is to power entire electronic systems, rather than single devices.

This research was nurtured by the Institute for Applied Life Sciences (IALS) at UMass Amherst, which combines deep and interdisciplinary expertise from 29 departments to translate fundamental research into innovations that benefit human health and well-being.

Journal Reference:

1. Xiaomeng Liu, Toshiyuki Ueki, Hongyan Gao, Trevor L. Woodard, Kelly P. Nevin, Tianda Fu, Shuai Fu, Lu Sun, Derek R. Lovley, Jun Yao. Microbial biofilms for electricity generation from water evaporation and power to wearables. Nature Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-32105-6 

Courtesy:

University of Massachusetts Amherst. "The bacteria powering a truly green revolution in personal electronics: Team engineers biofilm capable of producing long-term, continuous electricity from your sweat." ScienceDaily. ScienceDaily, 2 August 2022. <www.sciencedaily.com/releases/2022/08/220802153311.htm>.

 

 

Reframe the pain: Reducing needle anxiety in children

Tears, tantrums, and distress -- when it comes to needles, many children struggle with anxiety. But with vaccinations becoming more regular, finding ways to help reduce needle-related fear and pain is high on the agenda.

Now, new research from the University of South Australia shows that children's vaccination and needle fear can be lessened when nurses spend additional time supporting children in the vaccination process.

Working with children aged 8-12 years, the preliminary study found that two new nurse-led techniques show promise in reducing needle fear in primary-aged children:

• Divided Attention -- where a child's attention and expectations are drawn away from the needle.
• Positive Memory Reframing -- where a child's exaggerations about the distress and discomfort of needles are redressed through discussion about the positive elements of the experience so that the form more realistic memories of the event.

Lead researcher, UniSA's Dr Felicity Braithwaite, says helping children reduce fear and distress around vaccinations is a critical research priority given the current COVID-19 pandemic.

"For many children, undergoing a needle procedure can be painful and distressing," Dr Braithwaite says.

"Negative experiences of vaccinations in childhood can often lead to medical avoidance and vaccine hesitancy into adulthood, which can have devastating consequences when it comes to outbreaks of preventable diseases.

"By investing more time into techniques to help children manage their fears about needles, we hope to change these outcomes and deliver better health outcomes for the next generation."

The study involved 41 children and their parents, with participants randomly allocated to one of four groups -- usual care, divided attention, positive memory reframing, or a combination of the latter two interventions. Clinical outcomes were assessed at baseline, immediately post-vaccination and at two-weeks post-vaccination.

The Divided Attention technique involved a one-two minute distraction game where a nurse tapped the child's arm above and below the vaccination spot in a random order, with the child focussing their attention on guessing which spot was touched each time. This game takes advantage of the potential analgesic effects of distraction.

The Positive Memory Reframing technique involved talking to children about a past injection and emphasising positive aspects, such as how brave the child was and praising specific strategies they used to reduce their own distress, for example, deep breathing and looking away. The aim is to foster a sense of self-efficacy to help children better cope.

Both strategies were tested in non-clinical settings (such as schools) to maximise the potential of broad vaccination programs that deliver minimal distress for children.

Journal Reference:

1. Felicity A. Braithwaite, Melanie Noel, Hannah G. Jones, Michael D. Wiese, Cara G. Nania, Emily Watson, Tasha R. Stanton. Reframe the pain: Divided attention and positive memory reframing to reduce needle pain and distress in children—A feasibility randomized controlled trial. European Journal of Pain, 2022; 26 (8): 1702 DOI: 10.1002/ejp.1992 

Courtesy:

University of South Australia. "Reframe the pain: Reducing needle anxiety in children." ScienceDaily. ScienceDaily, 12 August 2022. <www.sciencedaily.com/releases/2022/08/220812113820.htm>.

 

Study finds why many IVF embryos fail to develop

In humans, a fertilized egg is no guarantee of reproductive success. Most embryos stop developing and perish within days of fertilization, usually because they have an abnormal number of chromosomes. Now, researchers at Columbia University Vagelos College of Physicians and Surgeons have found that most of these mistakes are due to spontaneous errors in DNA replication in the earliest phase of cell division.

The findings provide new insights into the basic biology of human reproduction and in the long term could lead to improvements in the success rate of in vitro fertilization (IVF). The study was published online July 19 in the journal Cell.

Challenging task for early embryos

Approximately 24 hours after a human egg is fertilized, the process of cell division begins. During cell division, the entire genome -- 46 chromosomes containing more than 3 billion base pairs of DNA -- must be faithfully duplicated. The duplicate sets of chromosomes must then be separated so that each daughter cell receives a complete set.

In many human embryos created for IVF, something goes wrong and some cells within the embryo have too few or too many chromosomes.

"Duplicating the genome is a challenging task for the early embryo," says study leader Dieter Egli, PhD, the Maimonides Assistant Professor of Developmental Cell Biology (in pediatrics) at Columbia University Vagelos College of Physicians and Surgeons.

Researchers have long theorized that errors occur during the final phase of cell division, when the duplicate sets of chromosomes separate into two identical daughter cells. Most of these failures were attributed to issues with the microtubule spindle, the apparatus that pulls the two sets of chromosomes apart.

But Egli's studies found that chromosomal abnormalities stem from errors that occur much earlier in the process of cell division when the genome's DNA is duplicated. If the DNA is not copied precisely, his studies found, the spindle malfunctions and places the wrong number of chromosomes into each daughter cell. When DNA duplication is abnormal, the spindle does not function normally. "This has largely been overlooked in previous studies -- because why would the embryo allow the integrity of the genome to be compromised when this is such a critical requirement for normal development?" Egli says.

Though the studies were conducted with embryos created in a petri dish -- including from individuals undergoing IVF and egg donors who were not seeking fertility treatment -- the same problems may contribute to the failure of embryos created in natural human reproduction.

Clues to source of DNA errors

The source of DNA copying errors in embryos appears to spring from obstacles within the DNA's double helix. Though the precise reason for these obstacles is not yet known, they cause duplication of the DNA to pause, or even stop, which results in DNA breakage and an abnormal number of chromosomes.

Spontaneous DNA errors can occur as early as the first cycle of cell division in human embryos, the researchers found, as well as in subsequent cell divisions. If too many cells in the early embryo are affected by chromosomal abnormalities, the embryo cannot develop further.

IVF

Most human embryos created for IVF stop developing within days after fertilization. This inefficiency of human development is an obstacle to successful fertility treatments.

"Many women undergoing fertility treatment require multiple IVF cycles in order to get pregnant, and some never get pregnant at all. Not only is this enormously expensive, it's emotionally taxing," says Jenna Turocy, MD, a fertility specialist at Columbia University Fertility Center and a co-author of the study.

The researchers are planning additional studies looking at DNA damage during replication in the hope of understanding normal and disease-causing variations in the human germ line. In the long term, these studies may lead to methods to reduce the risk of genetic abnormalities and embryo attrition for patients undergoing IVF.

More information

The study is titled, "Replication stress impairs chromosome segregation and preimplantation development in human embryos."

The other contributors (all Columbia unless noted) are: Katherine L. PalmerolaSelma Amrane, Alejandro De Los Angeles, Shuangyi Xu, Ning Wang, Joao de Pinho, Michael V. Zuccaro, Angelo Taglialatela, Dashiell J. Massey (Columbia and Cornell University), Alex Robles, Anisa Subbiah, Bob Prosser, Rogerio Lobo, Alberto Ciccia, Amnon Koren (Cornell), and Timour Baslan (Memorial Sloan Kettering Cancer Center).

This research was supported by a NYSCF-Robertson Stem Cell Investigator award and grants from the United States-Israel Binational Science Foundation, Columbia Stem Cell Initiative, the American Society for Reproductive Medicine, the John M. Driscoll Jr. Children's Fund Scholarship, and by the Russell Berrie Foundation Program in Cellular Therapies.

Dieter Egli is a member of the Cell editorial board.

Journal Reference:

1. Katherine L. Palmerola, Selma Amrane, Alejandro De Los Angeles, Shuangyi Xu, Ning Wang, Joao de Pinho, Michael V. Zuccaro, Angelo Taglialatela, Dashiell J. Massey, Jenna Turocy, Alex Robles, Anisa Subbiah, Bob Prosser, Rogerio Lobo, Alberto Ciccia, Amnon Koren, Timour Baslan, Dieter Egli. Replication stress impairs chromosome segregation and preimplantation development in human embryos. Cell, 2022; DOI: 10.1016/j.cell.2022.06.028

Courtesy:

Columbia University Irving Medical Center. "Study finds why many IVF embryos fail to develop." ScienceDaily. ScienceDaily, 19 July 2022. <www.sciencedaily.com/releases/2022/07/220719130213.htm>.

 

Common viruses may be triggering the onset of Alzheimer's disease

Alzheimer's disease can begin almost imperceptibly, often masquerading in the early months or years as forgetfulness that is common in older age. What causes the disease remains largely a mystery.

But researchers at Tufts University and the University of Oxford, using a three-dimensional human tissue culture model mimicking the brain, have shown that varicella zoster virus (VZV), which commonly causes chickenpox and shingles, may activate herpes simplex (HSV), another common virus, to set in motion the early stages of Alzheimer's disease.

Normally HSV-1 -- one of the main variants of the virus -- lies dormant within the neurons of the brain, but when it is activated it leads to accumulation of tau and amyloid beta proteins, and loss of neuronal function -- signature features found in patients with Alzheimer's.

"Our results suggest one pathway to Alzheimer's disease, caused by a VZV infection which creates inflammatory triggers that awaken HSV in the brain," said Dana Cairns, GBS12, a research associate in the Biomedical Engineering Department. "While we demonstrated a link between VZV and HSV-1 activation, it's possible that other inflammatory events in the brain could also awaken HSV-1 and lead to Alzheimer's disease."

The study is published in the Journal of Alzheimer's Disease.

Viruses Lying in Wait

"We have been working off a lot of established evidence that HSV has been linked to increased risk of Alzheimer's disease in patients," said David Kaplan, Stern Family Professor of Engineering and chair of the Department of Biomedical Engineering at Tufts' School of Engineering. One of the first to hypothesize a connection between herpes virus and Alzheimer's disease is Ruth Itzhaki of the University of Oxford, who collaborated with the Kaplan lab on this study.

"We know there is a correlation between HSV-1 and Alzheimer's disease, and some suggested involvement of VZV, but what we didn't know is the sequence of events that the viruses create to set the disease in motion," he said. "We think we now have evidence of those events."

According to the World Health Organization, an estimated 3.7 billion people under the age of 50 have been infected with HSV-1 -- the virus that causes oral herpes. In most cases it is asymptomatic, lying dormant within nerve cells.

When activated, it can cause inflammation in nerves and skin, causing painful open sores and blisters. Most carriers -- and that's one in two Americans according to the CDC -- will have between very mild to no symptoms before the virus becomes dormant.

Varicella zoster virus is also extremely common, with about 95 percent of people having been infected before the age of 20. Many of those cases are expressed as chicken pox. VZV, which is a form of herpes virus, can also remain in the body, finding its way to nerve cells before then becoming dormant.

Later in life, VZV can be reactivated to cause shingles, a disease characterized by blisters and nodules in the skin that form in a band-like pattern and can be very painful, lasting for weeks or even months. One in three people will eventually develop a case of shingles in their lifetime.

The link between HSV-1 and Alzheimer's disease only occurs when HSV-1 has been reactivated to cause sores, blisters, and other painful inflammatory conditions.

How Sleeping Viruses May Wake

To better understand the cause-and-effect relationship between the viruses and Alzheimer's disease, the Tufts researchers re-created brain-like environments in small 6 millimeter-wide donut-shaped sponges made of silk protein and collagen.

They populated the sponges with neural stem cells that grow and become functional neurons capable of passing signals to each other in a network, just as they do in the brain. Some of the stem cells also form glial cells, which are typically found in the brain and help keep the neurons alive and functioning.

The researchers found that neurons grown in the brain tissue can be infected with VZV, but that alone did not lead to the formation of the signature Alzheimer's proteins tau and beta-amyloid -- the components of the tangled mess of fibers and plaques that form in Alzheimer's patients' brains -- and that the neurons continued to function normally.

However, if the neurons already harbored quiescent HSV-1, the exposure to VZV led to a reactivation of HSV, and a dramatic increase in tau and beta-amyloid proteins, and the neuronal signals begin to slow down.

"It's a one-two punch of two viruses that are very common and usually harmless, but the lab studies suggest that if a new exposure to VZV wakes up dormant HSV-1, they could cause trouble," said Cairns.

"It's still possible that other infections and other pathways of cause and effect could lead to Alzheimer's disease, and risk factors such as head trauma, obesity, or alcohol consumption suggest they may intersect at the re-emergence of HSV in the brain," she added.

The researchers observed that the VZV infected samples started to produce a higher level of cytokines -- proteins which are often involved in triggering an inflammatory response. Kaplan noted that VZV is known in many clinical cases to cause inflammation in the brain, which could possibly lead to activation of dormant HSV and increased inflammation.

Repeat cycles of HSV-1 activation can lead to more inflammation in the brain, production of plaques, and accumulation of neuronal and cognitive damage.

A vaccine for VZV -- to prevent chickenpox and shingles -- has also been shown to considerably reduce the risk of dementia. It's possible that the vaccine is helping to stop the cycle of viral reactivation, inflammation, and neuronal damage.

The researchers also noted the long-term neurological effects that some COVID patients have experienced from the SARS-CoV-2 virus, particularly among the elderly, and that both VZV and HSV-1 can be reactivated after a COVID infection. Keeping an eye on possible follow-on cognitive effects and neurodegeneration would be advisable in these cases, they said.

Journal Reference:

1. Dana M. Cairns, Ruth F. Itzhaki, David L. Kaplan. Potential Involvement of Varicella Zoster Virus in Alzheimer’s Disease via Reactivation of Quiescent Herpes Simplex Virus Type 1. Journal of Alzheimer's Disease, 2022; 1 DOI: 10.3233/JAD-220287 

Courtesy:

Tufts University. "Common viruses may be triggering the onset of Alzheimer's disease: Shingles infection may activate dormant neurological herpes viruses, causing inflammation and accumulation of Alzheimer's associated proteins in the brain." ScienceDaily. ScienceDaily, 2 August 2022. <www.sciencedaily.com/releases/2022/07/220729173148.htm>.

 

Engineers develop stickers that can see inside the body

Ultrasound imaging is a safe and noninvasive window into the body's workings, providing clinicians with live images of a patient's internal organs. To capture these images, trained technicians manipulate ultrasound wands and probes to direct sound waves into the body. These waves reflect back out to produce high-resolution images of a patient's heart, lungs, and other deep organs.

Currently, ultrasound imaging requires bulky and specialized equipment available only in hospitals and doctor's offices. But a new design by MIT engineers might make the technology as wearable and accessible as buying Band-Aids at the pharmacy.

In a paper appearing today in Science, the engineers present the design for a new ultrasound sticker -- a stamp-sized device that sticks to skin and can provide continuous ultrasound imaging of internal organs for 48 hours.

The researchers applied the stickers to volunteers and showed the devices produced live, high-resolution images of major blood vessels and deeper organs such as the heart, lungs, and stomach. The stickers maintained a strong adhesion and captured changes in underlying organs as volunteers performed various activities, including sitting, standing, jogging, and biking.

The current design requires connecting the stickers to instruments that translate the reflected sound waves into images. The researchers point out that even in their current form, the stickers could have immediate applications: For instance, the devices could be applied to patients in the hospital, similar to heart-monitoring EKG stickers, and could continuously image internal organs without requiring a technician to hold a probe in place for long periods of time.

If the devices can be made to operate wirelessly -- a goal the team is currently working toward -- the ultrasound stickers could be made into wearable imaging products that patients could take home from a doctor's office or even buy at a pharmacy.

"We envision a few patches adhered to different locations on the body, and the patches would communicate with your cellphone, where AI algorithms would analyze the images on demand," says the study's senior author, Xuanhe Zhao, professor of mechanical engineering and civil and environmental engineering at MIT. "We believe we've opened a new era of wearable imaging: With a few patches on your body, you could see your internal organs."

The study also includes lead authors Chonghe Wang and Xiaoyu Chen, and co-authors Liu Wang, Mitsutoshi Makihata, and Tao Zhao at MIT, along with Hsiao-Chuan Liu of the Mayo Clinic in Rochester, Minnesota.

A sticky issue

To image with ultrasound, a technician first applies a liquid gel to a patient's skin, which acts to transmit ultrasound waves. A probe, or transducer, is then pressed against the gel, sending sound waves into the body that echo off internal structures and back to the probe, where the echoed signals are translated into visual images.

For patients who require long periods of imaging, some hospitals offer probes affixed to robotic arms that can hold a transducer in place without tiring, but the liquid ultrasound gel flows away and dries out over time, interrupting long-term imaging.

In recent years, researchers have explored designs for stretchable ultrasound probes that would provide portable, low-profile imaging of internal organs. These designs gave a flexible array of tiny ultrasound transducers, the idea being that such a device would stretch and conform with a patient's body.

But these experimental designs have produced low-resolution images, in part due to their stretch: In moving with the body, transducers shift location relative to each other, distorting the resulting image.

"Wearable ultrasound imaging tool would have huge potential in the future of clinical diagnosis. However, the resolution and imaging duration of existing ultrasound patches is relatively low, and they cannot image deep organs," says Chonghe Wang, who is an MIT graduate student.

An inside look

The MIT team's new ultrasound sticker produces higher resolution images over a longer duration by pairing a stretchy adhesive layer with a rigid array of transducers. "This combination enables the device to conform to the skin while maintaining the relative location of transducers to generate clearer and more precise images." Wang says.

The device's adhesive layer is made from two thin layers of elastomer that encapsulate a middle layer of solid hydrogel, a mostly water-based material that easily transmits sound waves. Unlike traditional ultrasound gels, the MIT team's hydrogel is elastic and stretchy.

"The elastomer prevents dehydration of hydrogel," says Chen, an MIT postdoc. "Only when hydrogel is highly hydrated can acoustic waves penetrate effectively and give high-resolution imaging of internal organs."

The bottom elastomer layer is designed to stick to skin, while the top layer adheres to a rigid array of transducers that the team also designed and fabricated. The entire ultrasound sticker measures about 2 square centimeters across, and 3 millimeters thick -- about the area of a postage stamp.

The researchers ran the ultrasound sticker through a battery of tests with healthy volunteers, who wore the stickers on various parts of their bodies, including the neck, chest, abdomen, and arms. The stickers stayed attached to their skin, and produced clear images of underlying structures for up to 48 hours. During this time, volunteers performed a variety of activities in the lab, from sitting and standing, to jogging, biking, and lifting weights.

From the stickers' images, the team was able to observe the changing diameter of major blood vessels when seated versus standing. The stickers also captured details of deeper organs, such as how the heart changes shape as it exerts during exercise. The researchers were also able to watch the stomach distend, then shrink back as volunteers drank then later passed juice out of their system. And as some volunteers lifted weights, the team could detect bright patterns in underlying muscles, signaling temporary microdamage.

"With imaging, we might be able to capture the moment in a workout before overuse, and stop before muscles become sore," says Chen. "We do not know when that moment might be yet, but now we can provide imaging data that experts can interpret."

The team is working to make the stickers function wirelessly. They are also developing software algorithms based on artificial intelligence that can better interpret and diagnose the stickers' images. Then, Zhao envisions ultrasound stickers could be packaged and purchased by patients and consumers, and used not only to monitor various internal organs, but also the progression of tumors, as well as the development of fetuses in the womb.

"We imagine we could have a box of stickers, each designed to image a different location of the body," Zhao says. "We believe this represents a breakthrough in wearable devices and medical imaging."

This research was funded, in part, by MIT, the Defense Advanced Research Projects Agency, the National Science Foundation, the National Institutes of Health, and the U.S. Army Research Office through the Institute for Soldier Nanotechnologies at MIT.

Video: https://youtu.be/Kn2J8W4csNc

 

Journal Reference:

1. Chonghe Wang, Xiaoyu Chen, Liu Wang, Mitsutoshi Makihata, Hsiao-Chuan Liu, Tao Zhou, Xuanhe Zhao. Bioadhesive ultrasound for long-term continuous imaging of diverse organs. Science, 2022; 377 (6605): 517 DOI: 10.1126/science.abo2542 

Courtesy:

Massachusetts Institute of Technology. "Engineers develop stickers that can see inside the body: New stamp-sized ultrasound adhesives produce clear images of heart, lungs, and other internal organs." ScienceDaily. ScienceDaily, 28 July 2022. <www.sciencedaily.com/releases/2022/07/220728142925.htm>.

 

Technology restores cell, organ function in pigs after death

Within minutes of the final heartbeat, a cascade of biochemical events triggered by a lack of blood flow, oxygen, and nutrients begins to destroy a body's cells and organs. But a team of Yale scientists has found that massive and permanent cellular failure doesn't have to happen so quickly.

Using a new technology they developed that delivers a specially designed cell-protective fluid to organs and tissues, the researchers restored blood circulation and other cellular functions in pigs a full hour after their deaths, they report in the Aug. 3 edition of the journal Nature.

The findings may help extend the health of human organs during surgery and expand availability of donor organs, the authors said.

"All cells do not die immediately, there is a more protracted series of events," said David Andrijevic, associate research scientist in neuroscience at Yale School of Medicine and co-lead author of the study. "It is a process in which you can intervene, stop, and restore some cellular function."

The research builds upon an earlier Yale-led project that restored circulation and certain cellular functions in the brain of a dead pig with technology dubbed BrainEx. Published in 2019, that study and the new one were led by the lab of Yale's Nenad Sestan, the Harvey and Kate Cushing Professor of Neuroscience and professor of comparative medicine, genetics, and psychiatry.

"If we were able to restore certain cellular functions in the dead brain, an organ known to be most susceptible to ischemia [inadequate blood supply], we hypothesized that something similar could also be achieved in other vital transplantable organs," Sestan said.

In the new study -- which involved senior author Sestan and colleagues Andrijevic, Zvonimir Vrselja, Taras Lysyy, and Shupei Zhang, all from Yale -- the researchers applied a modified version of BrainEx called OrganEx to the whole pig. The technology consists of a perfusion device similar to heart-lung machines -- which do the work of the heart and lungs during surgery -- and an experimental fluid containing compounds that can promote cellular health and suppress inflammation throughout the pig's body. Cardiac arrest was induced in anesthetized pigs, which were treated with OrganEx an hour after death.

Six hours after treatment with OrganEx, the scientists found that certain key cellular functions were active in many areas of the pigs' bodies -- including in the heart, liver, and kidneys -- and that some organ function had been restored. For instance, they found evidence of electrical activity in the heart, which retained the ability to contract.

"We were also able to restore circulation throughout the body, which amazed us," Sestan said.

Normally when the heart stops beating, organs begin to swell, collapsing blood vessels and blocking circulation, he said. Yet circulation was restored and organs in the deceased pigs that received OrganEx treatment appeared functional at the level of cells and tissue.

"Under the microscope, it was difficult to tell the difference between a healthy organ and one which had been treated with OrganEx technology after death," Vrselja said.

As in the 2019 experiment, the researchers also found that cellular activity in some areas of the brain had been restored, though no organized electrical activity that would indicate consciousness was detected during any part of the experiment.

The team was especially surprised to observe involuntary and spontaneous muscular movements in the head and neck areas when they evaluated the treated animals, which remained anesthetized through the entire six-hour experiment. These movements indicate the preservation of some motor functions, Sestan said.

The researchers stressed that additional studies are necessary to understand the apparently restored motor functions in the animals, and that rigorous ethical review from other scientists and bioethicists is required.

The experimental protocols for the latest study were approved by Yale's Institutional Animal Care and Use Committee and guided by an external advisory and ethics committee.

The OrganEx technology could eventually have several potential applications, the authors said. For instance, it could extend the life of organs in human patients and expand the availability of donor organs for transplant. It might also be able to help treat organs or tissue damaged by ischemia during heart attacks or strokes.

"There are numerous potential applications of this exciting new technology," said Stephen Latham, director of the Yale Interdisciplinary Center for Bioethics. "However, we need to maintain careful oversight of all future studies, particularly any that include perfusion of the brain."

The research was funded by the U.S. Department of Health & Human Services, National Institutes of Health, and National Institute of Mental Health.

This work was supported by the NIH grants MH117064, MH117064-01S1, R21DK128662, T32GM136651, F30HD106694, and Schmidt Futures.

Journal Reference:

1. Andrijevic, D., Vrselja, Z., Lysyy, T. et al. Cellular recovery after prolonged warm ischaemia of the whole body. Nature, 2022 DOI: 10.1038/s41586-022-05016-1 

courtesy:

Yale University. "Technology restores cell, organ function in pigs after death." ScienceDaily. ScienceDaily, 3 August 2022. <www.sciencedaily.com/releases/2022/08/220803112550.htm>.

 

 

Study finds why many IVF embryos fail to develop

In humans, a fertilized egg is no guarantee of reproductive success. Most embryos stop developing and perish within days of fertilization, usually because they have an abnormal number of chromosomes. Now, researchers at Columbia University Vagelos College of Physicians and Surgeons have found that most of these mistakes are due to spontaneous errors in DNA replication in the earliest phase of cell division.

The findings provide new insights into the basic biology of human reproduction and in the long term could lead to improvements in the success rate of in vitro fertilization (IVF). The study was published online July 19 in the journal Cell.

Challenging task for early embryos

Approximately 24 hours after a human egg is fertilized, the process of cell division begins. During cell division, the entire genome -- 46 chromosomes containing more than 3 billion base pairs of DNA -- must be faithfully duplicated. The duplicate sets of chromosomes must then be separated so that each daughter cell receives a complete set.

In many human embryos created for IVF, something goes wrong and some cells within the embryo have too few or too many chromosomes.

"Duplicating the genome is a challenging task for the early embryo," says study leader Dieter Egli, PhD, the Maimonides Assistant Professor of Developmental Cell Biology (in pediatrics) at Columbia University Vagelos College of Physicians and Surgeons.

Researchers have long theorized that errors occur during the final phase of cell division, when the duplicate sets of chromosomes separate into two identical daughter cells. Most of these failures were attributed to issues with the microtubule spindle, the apparatus that pulls the two sets of chromosomes apart.

But Egli's studies found that chromosomal abnormalities stem from errors that occur much earlier in the process of cell division when the genome's DNA is duplicated. If the DNA is not copied precisely, his studies found, the spindle malfunctions and places the wrong number of chromosomes into each daughter cell. When DNA duplication is abnormal, the spindle does not function normally. "This has largely been overlooked in previous studies -- because why would the embryo allow the integrity of the genome to be compromised when this is such a critical requirement for normal development?" Egli says.

Though the studies were conducted with embryos created in a petri dish -- including from individuals undergoing IVF and egg donors who were not seeking fertility treatment -- the same problems may contribute to the failure of embryos created in natural human reproduction.

Clues to source of DNA errors

The source of DNA copying errors in embryos appears to spring from obstacles within the DNA's double helix. Though the precise reason for these obstacles is not yet known, they cause duplication of the DNA to pause, or even stop, which results in DNA breakage and an abnormal number of chromosomes.

Spontaneous DNA errors can occur as early as the first cycle of cell division in human embryos, the researchers found, as well as in subsequent cell divisions. If too many cells in the early embryo are affected by chromosomal abnormalities, the embryo cannot develop further.

IVF

Most human embryos created for IVF stop developing within days after fertilization. This inefficiency of human development is an obstacle to successful fertility treatments.

"Many women undergoing fertility treatment require multiple IVF cycles in order to get pregnant, and some never get pregnant at all. Not only is this enormously expensive, it's emotionally taxing," says Jenna Turocy, MD, a fertility specialist at Columbia University Fertility Center and a co-author of the study.

The researchers are planning additional studies looking at DNA damage during replication in the hope of understanding normal and disease-causing variations in the human germ line. In the long term, these studies may lead to methods to reduce the risk of genetic abnormalities and embryo attrition for patients undergoing IVF.

More information

The study is titled, "Replication stress impairs chromosome segregation and preimplantation development in human embryos."

The other contributors (all Columbia unless noted) are: Katherine L. PalmerolaSelma Amrane, Alejandro De Los Angeles, Shuangyi Xu, Ning Wang, Joao de Pinho, Michael V. Zuccaro, Angelo Taglialatela, Dashiell J. Massey (Columbia and Cornell University), Alex Robles, Anisa Subbiah, Bob Prosser, Rogerio Lobo, Alberto Ciccia, Amnon Koren (Cornell), and Timour Baslan (Memorial Sloan Kettering Cancer Center).

This research was supported by a NYSCF-Robertson Stem Cell Investigator award and grants from the United States-Israel Binational Science Foundation, Columbia Stem Cell Initiative, the American Society for Reproductive Medicine, the John M. Driscoll Jr. Children's Fund Scholarship, and by the Russell Berrie Foundation Program in Cellular Therapies.

Dieter Egli is a member of the Cell editorial board.

Journal Reference:

1. Katherine L. Palmerola, Selma Amrane, Alejandro De Los Angeles, Shuangyi Xu, Ning Wang, Joao de Pinho, Michael V. Zuccaro, Angelo Taglialatela, Dashiell J. Massey, Jenna Turocy, Alex Robles, Anisa Subbiah, Bob Prosser, Rogerio Lobo, Alberto Ciccia, Amnon Koren, Timour Baslan, Dieter Egli. Replication stress impairs chromosome segregation and preimplantation development in human embryos. Cell, 2022; DOI: 10.1016/j.cell.2022.06.028 

Courtesy:

Columbia University Irving Medical Center. "Study finds why many IVF embryos fail to develop." ScienceDaily. ScienceDaily, 19 July 2022. <www.sciencedaily.com/releases/2022/07/220719130213.htm>.

 

 

Vitamin B6 supplements could reduce anxiety and depression

Taking high-dose Vitamin B6 tablets has been shown to reduce feelings of anxiety and depression by new research.

Scientists at the University of Reading measured the impact of high doses of Vitamin B6 on young adults and found that they reported feeling less anxious and depressed after taking the supplements every day for a month.

The study, published in the journal Human Psychopharmacology: Clinical and Experimental, provides valuable evidence to support the use of supplements thought to modify levels of activity in the brain for preventing or treating mood disorders.

Dr David Field, lead author from the School of Psychology and Clinical Language Sciences at the University of Reading, said: "The functioning of the brain relies on a delicate balance between the excitatory neurons that carry information around and inhibitory ones, which prevent runaway activity.

"Recent theories have connected mood disorders and some other neuropsychiatric conditions with a disturbance of this balance, often in the direction of raised levels of brain activity.

"Vitamin B6 helps the body produce a specific chemical messenger that inhibits impulses in the brain, and our study links this calming effect with reduced anxiety among the participants."

While previous studies have produced evidence that multivitamins or marmite can reduce stress levels, few studies have been carried out into which particular vitamins contained within them drive this effect.

The new study focused on the potential role of Vitamins B6, which is known to increase the body's production of GABA (Gamma-Aminobutyric Acid), a chemical that blocks impulses between nerve cells in the brain.

In the current trial, more than 300 participants were randomly assigned either Vitamin B6 or B12 supplements far above the recommended daily intake (approximately 50 times the recommended daily allowance) or a placebo, and took one a day with food for a month.

The study showed that Vitamin B12 had little effect compared to placebo over the trial period, but Vitamin B6 made a statistically reliable difference.

Raised levels of GABA among participants who had taken Vitamin B6 supplements were confirmed by visual tests carried out at the end of the trial, supporting the hypothesis that B6 was responsible for the reduction in anxiety. Subtle but harmless changes in visual performance were detected, consistent with controlled levels of brain activity.

Dr Field said: "Many foods, including tuna, chickpeas and many fruits and vegetables, contain Vitamin B6. However, the high doses used in this trial suggest that supplements would be necessary to have a positive effect on mood.

"It is important to acknowledge that this research is at an early stage and the effect of Vitamin B6 on anxiety in our study was quite small compared to what you would expect from medication. However, nutrition-based interventions produce far fewer unpleasant side effects than drugs, and so in the future people might prefer them as an intervention.

"To make this a realistic choice, further research is needed to identify other nutrition-based interventions that benefit mental wellbeing, allowing different dietary interventions to be combined in future to provide greater results.

"One potential option would be to combine Vitamin B6 supplements with talking therapies such as Cognitive Behavioural Therapy to boost their effect."

 

Journal Reference:

1. David T. Field, Rebekah O. Cracknell, Jessica R. Eastwood, Peter Scarfe, Claire M. Williams, Ying Zheng, Teresa Tavassoli. High‐dose Vitamin B6 supplementation reduces anxiety and strengthens visual surround suppression. Human Psychopharmacology: Clinical and Experimental, 2022; DOI: 10.1002/hup.2852 

Courtesy:

University of Reading. "Vitamin B6 supplements could reduce anxiety and depression." ScienceDaily. ScienceDaily, 19 July 2022. <www.sciencedaily.com/releases/2022/07/220719091209.htm>.