Tag: 20/6/24

Categories : Neurodegenerative DiseasesTags :

New Ultrasound and Genetics Combination Precisely Targets Neurons in Diseased Regions

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McKelvey School of Engineering researchers have developed a noninvasive technology combining a holographic acoustic device with genetic engineering that allows them to precisely target affected neurons in the brain, creating the potential to precisely modulate selected cell types in multiple diseased brain regions. (Credit: Yaoheng Yang)

Brain diseases such as Parkinson’s disease involve damage in more than one region of the brain, requiring technology that could precisely and flexibly address all affected regions simultaneously. Researchers have developed a noninvasive technology combining a holographic acoustic device with genetic engineering that allows them to precisely target affected neurons in the brain. This has the potential to precisely modulate selected cell types in multiple diseased brain regions. 

Hong Chen, associate professor of biomedical engineering and neurosurgery at Washington University in St. Louis and her team created AhSonogenetics, or Airy-beam holographic sonogenetics, a technique that uses a noninvasive wearable ultrasound device to alter genetically selected neurons in the brains of mice. Results of the proof-of-concept study were published in Proceedings of the National Academy of Sciences. 

AhSonogenetics brings together several of Chen’s group’s recent advances into one technology. In 2021, she and her team launched Sonogenetics, a method that uses focused ultrasound to deliver a viral construct containing ultrasound-sensitive ion channels to genetically selected neurons in the brain. They use low-intensity focused ultrasound to deliver a small burst of warmth, which opens the ion channels and activates the neurons. Chen’s team was the first to show that sonogenetics could modulate the behaviour of freely moving mice.

In 2022, she and members of her lab designed and 3D-printed a flexible and versatile tool known as an Airy beam-enabled binary acoustic metasurface that allowed them to manipulate ultrasound beams. She also is developing Sonogenetics 2.0, which combines the advantage of ultrasound and genetic engineering to modulate defined neurons noninvasively and precisely in the brains of humans and animals. AhSonogenetics brings them together as a potential method to intervene in neurodegenerative diseases. 

“By enabling precise and flexible cell-type-specific neuromodulation without invasive procedures, AhSonogenetics provides a powerful tool for investigating intact neural circuits and offers promising interventions for neurological disorders,” Chen said. 

Sonogenetics gives researchers a way to precisely control the brains, while airy-beam technology allows researchers to bend or steer the sound waves to generate arbitrary beam patterns inside the brain with a high spatial resolution. Yaoheng (Mack) Yang, a postdoctoral research associate who earned a doctorate in biomedical engineering from McKelvey Engineering in 2022, said the technology gives the researchers three unique advantages.

“Airy beam is the technology that can give us precise targeting of a smaller region than conventional technology, the flexibility to steer to the targeted brain regions, and to target multiple brain regions simultaneously,” Yang said.

Chen and her team, including first authors Zhongtao Hu, a former postdoctoral research associate, and Yang, designed each Airy-beam metasurface individually as the foundation for wearable ultrasound devices that were tailored for different applications and for precise locations in the brain.

Chen’s team tested the technique on a mouse model of Parkinson’s disease. With AhSonogenetics, they were able to stimulate two brain regions simultaneously in a single mouse, eliminating the need for multiple implants or interventions. This stimulation alleviated Parkinson’s-related motor deficits in the mouse model, including slow movements, difficulty walking and freezing behaviours.

The team’s Airy-beam device overcomes some of the limits of sonogenetics, including tailoring the design of the device to target specific brain locations, as well as incorporating the flexibility to adjust target locations in a single brain.

Hu said the device, which costs roughly $50 to make, can be tailored in size to fit various brain sizes, expanding its potential applications. 

“This technology can be used as a research platform to speed neuroscience research because of the capability to flexibly target different brain regions,” Hu said. “The affordability and ease of fabrication lower the barriers to the widespread adoption of our proposed devices by the research community for neuromodulation applications.”

Source: Washington University in St. Louis

Categories : HospitalsTags :

Wood May Have Natural Antiviral Properties

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Photo by National Cancer Institute on Unsplash

Thinking about getting a new desk for your practice? That might be a good idea. Viruses, including SARS-CoV-2, can get passed from person to person via contaminated surfaces. But can some surfaces reduce the risk of this type of transmission without the help of household disinfectants? As reported in ACS Applied Materials & Interfaces, wood has natural antiviral properties that can reduce the time viruses persist on its surface – and some species of wood are more effective than others at reducing infectivity.

Enveloped viruses, like the coronavirus, can live up to five days on surfaces; nonenveloped viruses, including enteroviruses linked to the common cold, can live for weeks, in some cases even if the surfaces are disinfected. Previous studies have shown that wood has antibacterial and antifungal properties, making it an ideal material for cutting boards. But wood’s ability to inactivate viruses has yet to be explored, which is what Varpu Marjomäki and colleagues set out to study.

The researchers looked at how long enveloped and nonenveloped viruses remained infectious on the surface of six types of wood: Scots pine, silver birch, gray alder, eucalyptus, pedunculate oak and Norway spruce. To determine viral activity, they flushed a wood sample’s surface with a liquid solution at different time points and then placed that solution in a petri dish that contained cultured cells. After incubating the cells with the solution, they measured the number (if any) infected with the virus.

Results from their demonstrations with an enveloped coronavirus showed that pine, spruce, birch and alder need one hour to completely reduce the virus’ ability to infect cells, with eucalyptus and oak needing two hours. Pine had the fastest onset of antiviral activity, beginning after five minutes. Spruce came in second, showing a sharp drop in infectivity after 10 minutes.

For a nonenveloped enterovirus, the researchers found that incubation on oak and spruce surfaces resulted in a loss of infectivity within about an hour, with oak having an onset time of 7.5 minutes and spruce after 60 minutes. Pine, birch and eucalyptus reduced the virus’ infectivity after four hours, and alder showed no antiviral effect.

Based on their study data, the researchers concluded that the chemical composition of a wood’s surface is primarily responsible for its antiviral functionality. While determining the exact chemical mechanisms responsible for viral inactivation will require further study, they say these findings point to wood as a promising potential candidate for sustainable, natural antiviral materials.

Source: American Chemical Society

Categories : Cardiovascular DiseaseTags :

Popular OTC Supplement Improves Walking in Peripheral Artery Disease

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Photo by Miikka Luotio on Unsplash

The over-the-counter supplement nicotinamide riboside, a form of vitamin B3, increased the walking endurance of patients with peripheral artery disease, a chronic leg condition for which there are few effective treatments. 

In a preliminary, randomised, double-blind clinical trial led by Northwestern University and University of Florida scientists, patients who took nicotinamide riboside daily for six months increased their timed walking distance by more than 17.3m, compared to a placebo group. As expected, walking speed declined in the placebo group, because peripheral artery disease causes progressive declines in walking performance. 

“This is a signal that nicotinamide riboside could help these patients,” said Christiaan Leeuwenburgh, PhD, a UF professor of physiology and aging and senior author of the clinical trial report. “We are hoping to conduct a larger follow-up trial to verify our findings.”

Along with other researchers, Leeuwenburgh, whose research specialises in anti-aging treatments, collaborated with Mary M. McDermott, MD, a physician and professor of medicine at Northwestern University and an expert in peripheral artery disease.

The scientists recruited 90 people with an average age of 71 who had peripheral artery disease, or PAD, to test the effects of nicotinamide riboside. The supplement is increasingly popular as an anti-aging treatment (sales exceeded $60 million in 2022 in the US alone) but there has been scant evidence of any benefit in healthy people. Nicotinamide riboside is a precursor for the essential compound NAD, which plays roles in the body related to energy generation, improved blood flow and DNA repair.

Because PAD is associated with problems generating energy within muscle cells, McDermott and Leeuwenburgh thought that nicotinamide riboside, by improving energy generation, could help improve walking in people with the disease.

And indeed that’s what they found. Participants taking the supplement walked an average of 7m more in a six-minute walking test after six months, while those taking a placebo walked 10.3m less. Those who took at least 75% of the pills they were supposed to take performed even better, adding more than 30m to their walking distance, compared to people who took a placebo.

(The researchers also tested if resveratrol, a compound best known for being in red wine, could boost the effects of nicotinamide riboside; they found no additional benefits.)

PAD affects more than 8.5 million Americans over the age of 40. Caused by the buildup of fatty deposits in arteries, and associated with diabetes and smoking, the disease reduces blood flow to the limbs, especially the legs. Walking often becomes painful, and the disease typically causes declines in walking ability over time. Supervised walking exercise is first line therapy for PAD, but most people with the condition do not have access to supervised exercise. 

In addition to a larger trial focused on patients suffering from PAD, Leeuwenburgh hopes to test the effects of nicotinamide riboside on walking performance in healthy older adults. 

“We need to test it on a healthy older population before we recommend healthy people take it,” he said.

Source: University of Florida

Categories : GeneticsTags :

Genetic Study of Coffee’s Mental Health Links has Contradictory Results

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Photo by Mike Kenneally on Unsplash

Coffee drinking is a heritable habit, and one that carries a certain amount of genetic baggage. Caffeinated coffee is a psychoactive substance, notes Sandra Sanchez-Roige, PhD, an associate professor at University of California San Diego. She is the corresponding author of a study published in the journal Neuropsychopharmacology that compared coffee-consumption characteristics from a 23andMe database in the United States with the UK Biobank.

Lead author Hayley H. A. Thorpe, PhD, at Western University in Ontario, explained that the team collected genetic data as well as self-reported coffee-consumption numbers to assemble a genome-wide association study (GWAS). The idea was to make connections between the genes that were known to be associated with coffee consumption and the traits or conditions related to health.

“We used this data to identify regions on the genome associated with whether somebody is more or less likely to consume coffee,” Thorpe explained. “And then identify the genes and biology that could underlie coffee intake.”

UC San Diego professor Abraham Palmer, PhD is also a lead researcher on the paper. He said that most people are surprised that there is a genetic influence on coffee consumption. “We had good reason to suspect from earlier papers that there were genes that influence how much coffee someone consumes,” he said. “And so, we weren’t surprised to find that in both of the cohorts we examined there was statistical evidence that this is a heritable trait. In other words, the particular gene variants that you inherit from your parents influence how much coffee you’re likely to consume.”

Sanchez-Roige said the genetic influence on coffee consumption was the first of two questions the researchers wanted to address.

“The second is something that coffee lovers are really keen on learning,” Sanchez-Roige said. “Is drinking coffee good or bad? Is it associated with positive health outcomes or not?”

The answer is not definitive. The group’s genome-wide association study of 130 153 U.S.-based 23andMe research participants was compared with a similar UK Biobank database of 334 649 Britons, revealing consistent positive genetic associations between coffee and harmful health outcomes such as obesity and substance use. A positive genetic association is a connection between a specific gene variant (the genotype) and a specific condition (the phenotype). Conversely, a negative genetic association is an apparent protective quality discouraging the development of a condition. The findings get more complicated when it comes to psychiatric conditions.

“Look at the genetics of anxiety, for instance, or bipolar and depression: In the 23andMe data set, they tend to be positively genetically correlated with coffee intake genetics,” Thorpe said. “But then, in the UK Biobank, you see the opposite pattern, where they’re negatively genetically correlated. This is not what we expected.”

She said there were other instances in which the 23andMe set didn’t align with the UK Biobank, but the greatest disagreement was in psychiatric conditions.

“It’s common to combine similar datasets in this field to increase study power. This information paints a fairly clear picture that combining these two datasets was really not a wise idea. And we didn’t end up doing that,” Thorpe said. She explained that melding the databases might mask effects, leading researchers toward incorrect conclusions – or even cancelling each other out.

Sanchez-Roige says the researchers have some ideas about how the differences in results arose. To begin with, there was an apples-and-oranges aspect to the surveys. For instance, the 23andMe survey asked, “How many 5-ounce (cup-sized) servings of caffeinated coffee do you consume each day?” Compare it to the UK Biobank’s “How many cups of coffee do you drink each day? (Include decaffeinated coffee)”

Beyond serving size and the caffeinated/decaf divide, the surveys made no accommodation for the various ways coffee is served. “We know that in the U.K., they have generally higher preference for instant coffee, whereas ground coffee is more preferred in the U.S.,” Thorpe said.

“And then there’s the frappuccinos,” Sanchez-Roige added, citing the American trend of taking coffee loaded with sugary additives. Palmer mentioned other caffeinated drinks and especially in the context of the UK Biobank, tea, none of which were included in the GWAS, which addressed only coffee. Palmer added that the GWAS demonstrates the relationship between genotype and phenotype is more different than the relationship between coffee and tea.

“Genetics influences lots of things. For instance, it influences how tall you might be,” he said. “And those kinds of things probably would play out very similarly, whether you lived in the US or the UK But coffee is a decision that people make.”

Sanchez-Roige pointed out that coffee comes in a variety of forms, from instant to frappuccino, and is consumed amid cultural norms that differ from place to place. A person with a given genotype might end up having quite a different phenotype living in the UK versus the US.

“And that’s really what the data are telling us,” she said. “Because unlike height, where your behaviour doesn’t really have much to do with it, your behaviour and the choices you’re making in your environment play out in various ways. So the interaction between genotype and environment complicates the picture.”

The collaborators stressed the need for more investigation to unravel the relationships between genetics and the environment, focusing not only on coffee/caffeine intake but also other substance-use issues.

Source: University of California San Diego

Categories : PaediatricsTags :

Anaemia Reduction Efforts to Improve School Attendance may be Ineffective

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Photo by Mary Taylor on Pexels

In low- and middle-income countries, anaemia reduction efforts are often touted as a way to improve educational outcomes and reduce poverty. A new study, published in Communications Medicine, evaluates the relationship between anaemia and school attendance in India, debunking earlier research that could have misguided policy interventions.

Kumar’s research explores the intersection of global health and poverty reduction. His latest work evaluates the relationship between anaemia and school attendance in India.

The study investigated whether there was a link between anaemia and school attendance in more than 250 000 adolescents ages 15 to 18. Earlier observational studies have shown a link between anaemia and attendance, even after accounting for variables such as gender and household wealth, according to Kumar. But the new study, which applied more rigorous econometric statistical analysis, did not find such a link, he said.

“Most previous research on this topic has used conventional study designs or focused on small geographical areas, which limits its policy relevance,” said study co-author Santosh Kumar, associate professor of development and global health economics at the University of Notre Dame, is co-author of the study. “Earlier estimates may have been distorted by unobserved household factors related to both anaemia and school attendance. So in this study, we focused on the relationship between anaemia and attendance among adolescents who were living in the same household.

“Ultimately,” Kumar said, “we found that the link between anaemia and schooling is more muted than previously suggested by studies that did not consider household-level factors.”

The findings have important implications for policymakers seeking to improve education in low- and middle-income countries like India, Kumar said. India has widespread school attendance issues and struggles with health conditions such as anaemia caused by iron deficiency, particularly in children and adolescents. The country has pushed to improve educational outcomes, in keeping with the United Nations’ Sustainable Development Goals, Kumar said. But to achieve that, he said, more research is needed to pinpoint an evidence-based intervention.

The latest study builds on an earlier one in which Kumar and fellow researchers helped evaluate the results of an iron fortification school lunch program for students ages 7 and 8 in India. That study showed that fortification reduced anaemia but did not affect students’ performance in school. A forthcoming study, set to launch in summer 2024, will look at iron fortification for children ages 3 to 5. The research hypothesis is that an early-age nutritional intervention among preschoolers would make a significant impact on physical and cognitive development.

“Our findings have implications for policymakers who want to improve educational outcomes and reduce poverty,” Kumar said. “Effective policies are based on evidence. We need more rigorous statistical analysis to examine the causal relationship between anaemia and education.

“This work ties into my larger research agenda, which explores the intersection of global health and poverty reduction. I want to use my academic research to support human dignity by helping to identify evidence-based health policies that will make a tangible difference in people’s lives.”

Source: University of Notre Dame

Categories : Gastrointestinal Neurodegenerative DiseasesTags :

Gut Bacteria in Parkinson’s Disease Produce Fewer B Vitamins

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In Parkinson’s disease, a reduction in the gut bacteria of genes responsible for synthesising the essential B vitamins B2 and B7 was found. Credit: Reiko Matsushita

A study led by Nagoya University in Japan has revealed a link between gut microbiota and Parkinson’s disease (PD). The researchers found that the gut bacteria genes responsible for synthesising vitamins B2 and B7 were reduced. This gene reduction was also linked to low levels of agents that help maintain the integrity of the intestinal barrier, which when weakened causes the inflammation seen in PD. Their findings, published in npj Parkinson’s Disease, suggest that treatment with B vitamins to address these deficiencies can be used to treat PD. 

PD is characterized by a variety of physical symptoms that hinder daily activities and mobility, such as shaking, slow movement, stiffness, and balance problems. While the frequency of PD may vary between different populations, it is estimated to affect approximately 1-2% of individuals aged 55 years or older. 

Various physiological processes are heavily influenced by the microorganisms found in the gut, which are collectively known as gut microbiota. In ideal conditions, gut microbiota produce SCFAs and polyamines, which maintain the intestinal barrier that prevents toxins entering the bloodstream. Toxins in the blood can be carried to the brain where they cause inflammation and affect neurotransmission processes that are critical for maintaining mental health.

To better understand the relationship between the microbial characteristics of the gut in PD, Hiroshi Nishiwaki and Jun Ueyama from the Nagoya University Graduate School of Medicine conducted a metanalysis of stool samples from patients with PD from Japan, the United States, Germany, China, and Taiwan. They used shotgun sequencing, a technique that sequences all genetic material in a sample. This is an invaluable tool because it offers researchers a better understanding of the microbial community and genetic makeup of the sample.

They observed a decrease in the bacterial genes responsible for the synthesising of riboflavin (vitamin B2) and biotin (vitamin B7) in patients diagnosed with PD. Riboflavin and biotin, derived from both food and gut microbiota, have anti-inflammatory properties, which may counteract the neuroinflammation seen in diseases like PD. 

B vitamins play crucial roles in the metabolic processes that influence the production and functions of short-chain fatty acids (SCFAs) and polyamines, two agents that help maintain the integrity of the intestinal barrier, preventing toxins entering the bloodstream. An examination of fecal metabolites revealed decreases of both in patients with PD. 

The findings indicate a potential explanation for the progression of PD. “Deficiencies in polyamines and SCFAs could lead to thinning of the intestinal mucus layer, increasing intestinal permeability, both of which have been observed in PD,” Nishiwaki explained. “This higher permeability exposes nerves to toxins, contributing to abnormal aggregation of alpha-synuclein, activating the immune cells in the brain, and leading to long-term inflammation.” 

He added, “Supplementation therapy targeting riboflavin and biotin holds promise as a potential therapeutic avenue for alleviating PD symptoms and slowing disease progression.”

The results of the study highlight the importance of understanding the complex relationship among gut microbiota, metabolic pathways, and neurodegeneration. In the coming years, customised therapy could potentially be based on patients’ unique microbiome profiles. By altering bacterial levels in the microbiome, doctors can potentially delay the onset of symptoms associated with diseases like PD.

“We could perform gut microbiota analysis on patients or conduct faecal metabolite analysis,” Nishiwaki said. “Using these findings, we could identify individuals with specific deficiencies and administer oral riboflavin and biotin supplements to those with decreased levels, potentially creating an effective treatment.”

Source: Nagoya University

The study, “Meta-analysis of shotgun sequencing of gut microbiota in Parkinson’s disease,” was published in npj Parkinson’s Disease on May 21, 2024, at DOI:10.1038/s41531-024-00724-z.