ADHD and ASD: What the eyes could reveal

 

It's often said that 'the eyes tell it all', but no matter what their outward expression, the eyes may also be able to signal neurodevelopmental disorders such as ASD and ADHD according to new research from Flinders University and the University of South Australia.

In the first study of its kind, researchers found that recordings from the retina could identify distinct signals for both Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) providing a potential biomarker for each condition.

Using the 'electroretinogram' (ERG) -- a diagnostic test that measures the electrical activity of the retina in response to a light stimulus -- researchers found that children with ADHD showed higher overall ERG energy, whereas children with ASD showed less ERG energy.

Research optometrist at Flinders University, Dr Paul Constable, says the preliminary findings indicate promising results for improved diagnoses and treatments in the future.

"ASD and ADHD are the most common neurodevelopmental disorders diagnosed in childhood. But as they often share similar traits, making diagnoses for both conditions can be lengthy and complicated," Dr Constable says.

"Our research aims to improve this. By exploring how signals in the retina react to light stimuli, we hope to develop more accurate and earlier diagnoses for different neurodevelopmental conditions.

"Retinal signals have specific nerves that generate them, so if we can identify these differences and localise them to specific pathways that use different chemical signals that are also used in the brain, then we can show distinct differences for children with ADHD and ASD and potentially other neurodevelopmental conditions."

"This study delivers preliminary evidence for neurophysiological changes that not only differentiate both ADHD and ASD from typically developing children, but also evidence that they can be distinguished from each other based on ERG characteristics."

According to the World Health Organization, one in 100 children has ASD, with 5-8 per cent of children diagnosed with ADHD.

Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental condition characterised by being overly active, struggling to pay attention, and difficulty controlling impulsive behaviours. Autism spectrum disorder (ASD) is also a neurodevelopmental condition where children behave, communicate, interact, and learn in ways that are different from most other people.

Co-researcher and expert in human and artificial cognition at the University of South Australia, Dr Fernando Marmolejo-Ramos, says the research has potential to extend across other neurological conditions.

"Ultimately, we're looking at how the eyes can help us understand the brain," Dr Marmolejo-Ramos says.

"While further research is needed to establish abnormalities in retinal signals that are specific to these and other neurodevelopmental disorders, what we've observed so far shows that we are on the precipice of something amazing.

"It is truly a case of watching this space; as it happens, the eyes could reveal all."

This research was conducted in partnership with McGill University, University College London and the Great Ormond Street Hospital for Children.

 

Journal Reference:

1. Paul A. Constable, Fernando Marmolejo-Ramos, Mercedes Gauthier, Irene O. Lee, David H. Skuse, Dorothy A. Thompson. Discrete Wavelet Transform Analysis of the Electroretinogram in Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder. Frontiers in Neuroscience, 2022; 16 DOI: 10.3389/fnins.2022.890461 

Courtesy:

University of South Australia. "ADHD and ASD: What the eyes could reveal." ScienceDaily. ScienceDaily, 17 June 2022. <www.sciencedaily.com/releases/2022/06/220617101604.htm>.

 

Visible light triggers molecular machines to treat infections

 

Molecular machines that kill infectious bacteria have been taught to see their mission in a new light.

The latest iteration of nanoscale drills developed at Rice University are activated by visible light rather than ultraviolet (UV), as in earlier versions. These have also proven effective at killing bacteria through tests on real infections.

Six variants of molecular machines were successfully tested by Rice chemist James Tour and his team. All of them punched holes in the membranes of gram-negative and gram-positive bacteria in as little as two minutes. Resistance was futile for bacteria that have no natural defenses against mechanical invaders. That means they are unlikely to develop resistance, potentially offering a strategy to defeat bacteria that have become immune to standard antibacterial treatments over time.

"I tell students that when they are my age, antibiotic-resistant bacteria are going to make COVID look like a walk in the park," Tour said. "Antibiotics won't be able to keep 10 million people a year from dying of bacterial infections. But this really stops them."

The breakthrough study led by Tour and Rice alumni Ana Santos and Dongdong Liu appears in Science Advances.

Because extended exposure to UV can be damaging to humans, the Rice lab has been refining its molecules for years. The new version gets its energy from still-blueish light at 405 nanometers, spinning the molecules' rotors at 2 to 3 million times per second.

It's been suggested by other researchers that light at that wavelength has mild antibacterial properties of its own, but the addition of molecular machines supercharges it, said Tour, who suggested bacterial infections like those suffered by burn victims and people with gangrene will be early targets.

The machines are based on Nobel Prize-winning work by Bernard Feringa, who developed the first molecule with a rotor in 1999 and got the rotor to spin reliably in one direction. Tour and his team introduced their advanced drills in a 2017 Nature paper.

The Rice lab's first tests of the new molecules on burn wound infection models confirmed their ability to quickly kill bacteria, including methicillin-resistant Staphylococcus aureus, a common cause of skin and soft tissue infections that was responsible for more than 100,000 deaths in 2019.

The team achieved visible light activation by adding a nitrogen group. "The molecules were further modified with different amines in either the stator (stationary) or the rotor portion of the molecule to promote the association between the protonated amines of the machines and the negatively charged bacterial membrane," said Liu, now a scientist at Arcus Biosciences in California.

The researchers also found the machines effectively break up biofilms and persister cells, which become dormant to avoid antibacterial drugs.

"Even if an antibiotic kills most of a colony, there are often a few persister cells that for some reason don't die," Tour said. "But that doesn't matter to the drills."

As with earlier versions, the new machines also promise to revive antibacterial drugs considered ineffective. "Drilling through the microorganisms' membranes allows otherwise ineffective drugs to enter cells and overcome the bug's intrinsic or acquired resistance to antibiotics," said Santos, who's on the third year of the postdoctoral global fellowship that brought her to Rice for two years and is continuing at the Health Research Institute of the Balearic Islands in Palma, Spain.

The lab is working toward better targeting of bacteria to minimize damage to mammalian cells by linking bacteria-specific peptide tags to the drills to direct them toward pathogens of interest. "But even without that, the peptide can be applied to a site of bacterial concentration, like in a burn wound area," Santos said.

Co-authors are Rice alumni Anna Reed and John Li, senior Aaron Wyderka, graduate students Alexis van Venrooy and Jacob Beckham, researcher Victor Li, postdoctoral alumni Mikita Misiura and Olga Samoylova, research scientist Ciceron Ayala-Orozco, lecturer Lawrence Alemany and Anatoly Kolomeisky, a professor of chemistry; Antonio Oliver of the Health Research Institute of the Balearic Islands and the Son Espases University Hospital, Palma, Spain; and George Tegos of Tower Health, Reading, Pennsylvania.

Tour is the T.T. and W.F. Chao Professor of Chemistry and a professor of materials science and nanoengineering.

The European Union's Horizon 2020 research and innovation program (843116), the Discovery Institute and the Robert A. Welch Foundation (C-2017-20190330) supported the research.

 

Journal Reference:

1. Ana L. Santos, Dongdong Liu, Anna K. Reed, Aaron M. Wyderka, Alexis van Venrooy, John T. Li, Victor D. Li, Mikita Misiura, Olga Samoylova, Jacob L. Beckham, Ciceron Ayala-Orozco, Anatoly B. Kolomeisky, Lawrence B. Alemany, Antonio Oliver, George P. Tegos, James M. Tour. Light-activated molecular machines are fast-acting broad-spectrum antibacterials that target the membrane. Science Advances, 2022; 8 (22) DOI: 10.1126/sciadv.abm2055

Courtesy:

Rice University. "Visible light triggers molecular machines to treat infections." ScienceDaily. ScienceDaily, 1 June 2022. <www.sciencedaily.com/releases/2022/06/220601142804.htm>.

 

Biochemistry researchers repair and regenerate heart muscle cells

Researchers at the University of Houston are reporting a first-of-its-kind technology that not only repairs heart muscle cells in mice but also regenerates them following a heart attack, or myocardial infarction as its medically known.

Published in the Journal of Cardiovascular Aging, the groundbreaking finding has the potential to become a powerful clinical strategy for treating heart disease in humans, according to Robert Schwartz, Hugh Roy and Lillie Cranz Cullen Distinguished Professor of biology and biochemistry at the UH College of Natural Sciences and Mathematics.

The new technology developed by the team of researchers uses synthetic messenger ribonucleic acid (mRNA) to deliver mutated transcription factors -- proteins that control the conversion of DNA into RNA -- to mouse hearts.

"No one has been able to do this to this extent and we think it could become a possible treatment for humans," said Schwartz, who led the study with recent Ph.D graduate Siyu Xiao and Dinakar Iyer, a research assistant professor of biology and biochemistry.

Synthetic mRNA Contributes to Stem Cell-Like Growth

The researchers demonstrated that two mutated transcription factors, Stemin and YAP5SA, work in tandem to increase the replication of cardiomyocytes, or heart muscle cells, isolated from mouse hearts. These experiments were conducted in vitro on tissue culture dishes.

"What we are trying to do is dedifferentiate the cardiomyocyte into a more stem cell-like state so that they can regenerate and proliferate," Xiao said.

Stemin turns on stem cell-like properties from cardiomyocytes. Stemin's crucial role in their experiments was discovered by Iyer, who said the transcription factor was a "game changer." Meanwhile, YAP5SA works by promoting organ growth that causes the myocytes to replicate even more.

In a separate finding published in the same journal, the team will report that Stemin and YAP5SA repaired damaged mouse hearts in vivo. Notably, myocyte nuclei replicated at least 15-fold in 24 hours following heart injections that delivered those transcription factors.

Bradley McConnell, professor of pharmacology, and graduate student Emilio Lucero in the UH College of Pharmacy, collaborated on the study by producing the infarcted adult mouse model.

"When both transcription factors were injected into infarcted adult mouse hearts, the results were stunning," Schwartz said. "The lab found cardiac myocytes multiplied quickly within a day, while hearts over the next month were repaired to near normal cardiac pumping function with little scarring."

An added benefit of using synthetic mRNA, according to Xiao, is that it disappears in a few days as opposed to viral delivery. Gene therapies delivered to cells by viral vectors raise several biosafety concerns because they cannot be easily stopped. mRNA-based delivery, on the other hand, turns over quickly and disappears.

A Limited Number of Cardiomyocytes

Schwartz and Iyer worked on this study for several years, and Xiao focused on this research throughout her doctoral studies at UH. She graduated in fall 2020.

"I feel honored and lucky to have worked on this," Xiao said. "This is a huge study in heart regeneration especially given the smart strategy of using mRNA to deliver Stemin and YAP5SA."

The findings are especially important because less than 1% of adult cardiac muscle cells can regenerate. "Most people die with most of the same cardiomyocytes they had in the first month of life," she said. When there is a heart attack and heart muscle cells die, the contracting ability of the heart can be lost.

The study was funded in part through the University of Houston, a Cullen Endowed Chair, the Texas Higher Education Coordinating Board, Leducq Foundation and a sponsored research agreement from Animatus Biosciences, LLC.

Other study contributors include Rui Lang from UH; and Zhishi Chen and Jiang Chang from the Texas A&M Institute of Biosciences and Technology.

Journal Reference:

1. Siyu Xiao, Rui Liang, Azeez B. Muili, Xuanye Cao, Stephen Navran, Robert J. Schwartz, Dinakar Iyer. Mutant SRF and YAP synthetic modified mRNAs drive cardiomyocyte nuclear replication. The Journal of Cardiovascular Aging, 2022; 2 (3): 29 DOI: 10.20517/jca.2022.17

 

 Courtesy:

University of Houston. "Biochemistry researchers repair and regenerate heart muscle cells: Discovery has potential to become 'powerful clinical strategy' for treating heart disease." ScienceDaily. ScienceDaily, 16 June 2022. <www.sciencedaily.com/releases/2022/06/220616142756.htm>.

Study identifies receptor that could alleviate need for chemo, radiation pre-T cell therapy

Before a patient can undergo T cell therapy designed to target cancerous tumors, the patient's entire immune system must be destroyed with chemotherapy or radiation. The toxic side effects are well known, including nausea, extreme fatigue and hair loss.

Now a research team, led by UCLA's Anusha Kalbasi, MD, in collaboration with scientists from Stanford and the University of Pennsylvania, has shown that a synthetic IL-9 receptor allows those cancer-fighting T cells to do their work without the need for chemo or radiation. T cells engineered with the synthetic IL-9 receptor, designed in the laboratory of Christopher Garcia, PhD, at Stanford, were potent against tumors in mice, as published Wednesday in Nature.

"When T cells are signaling through the synthetic IL-9 receptor, they gain new functions that help them not only outcompete the existing immune system but also kill cancer cells more efficiently," Kalbasi said. "I have a patient right now struggling through toxic chemotherapy just to wipe out his existing immune system so T cell therapy can have a fighting chance. But with this technology you might give T cell therapy without having to wipe out the immune system beforehand."

Kalbasi, a researcher at the UCLA Jonsson Comprehensive Cancer Center and an assistant professor of radiation oncology at the David Geffen School of Medicine at UCLA, began the work while under the mentorship of Antoni Ribas, MD, PhD, a senior investigator on the study. The study was also led by Mikko Siurala, PhD, from the laboratory of Carl June, MD, at Penn, and Leon L. Su, PhD, of the Garcia Lab at Stanford.

"This finding opens a door for us to be able to give T cells a lot like we give a blood transfusion," Ribas said.

Ribas and Garcia collaborated on a paper published in 2018 that focused on the concept that a synthetic version of interleukin-2 (IL-2), a critical T cell growth cytokine, could be used to stimulate T cells engineered with a matching synthetic receptor for the synthetic IL-2. With this system, T cells can be manipulated even after they have been given to a patient, by treating the patient with the synthetic cytokine (which has no effect on other cells in the body). Intrigued by that work, Kalbasi and colleagues were interested in testing modified versions of the synthetic receptor that transmit other cytokine signals from the common-gamma chain family: IL-4, -7, -9 and -21.

"It was clear early on that, among the synthetic common-gamma chain signals, the IL-9 signal was worth investigating," Kalbasi said, adding that unlike other common-gamma chain cytokines, IL-9 signaling is not typically active in naturally occurring T cells. The synthetic IL-9 signal made T cells take on a unique mix of both stem-cell and killer-like qualities that made them more robust in fighting tumors. "In one of our cancer models, we cured over half the mice that were treated with the synthetic IL-9 receptor T cells."

Kalbasi said the therapy proved to be effective in multiple systems. They targeted two types of hard-to-treat cancer models in mice -- pancreatic cancer and melanoma -- and used T cells targeted to cancer cells through the natural T cell receptor or a chimeric antigen receptor (CAR). "The therapy also worked whether we gave the cytokine to the whole mouse or directly to the tumor. In all cases, T cells engineered with synthetic IL-9 receptor signaling were superior and helped us cure some tumors in mice when we couldn't do it otherwise."

 

Journal Reference:

1. Anusha Kalbasi, Mikko Siurala, Leon L. Su, Mito Tariveranmoshabad, Lora K. Picton, Pranali Ravikumar, Peng Li, Jian-Xin Lin, Helena Escuin-Ordinas, Tong Da, Sarah V. Kremer, Amy L. Sun, Sofia Castelli, Sangya Agarwal, John Scholler, Decheng Song, Philipp C. Rommel, Enrico Radaelli, Regina M. Young, Warren J. Leonard, Antoni Ribas, Carl H. June, K. Christopher Garcia. Potentiating adoptive cell therapy using synthetic IL-9 receptors. Nature, 2022; DOI: 10.1038/s41586-022-04801-2 

Courtesy:

University of California - Los Angeles Health Sciences. "Study identifies receptor that could alleviate need for chemo, radiation pre-T cell therapy." ScienceDaily. ScienceDaily, 8 June 2022. <www.sciencedaily.com/releases/2022/06/220608161436.htm>.

 

Most 'silent' genetic mutations are harmful, not neutral -- a finding with broad implications

In the early 1960s, University of Michigan alumnus Marshall Nirenberg and a few other scientists deciphered the genetic code of life, determining the rules by which information in DNA molecules is translated into proteins, the working parts of living cells.

They identified three-letter units in DNA sequences, known as codons, that specify each of the 20 amino acids that make up proteins, work for which Nirenberg later shared a Nobel Prize with two others.

Occasionally, single-letter misspellings in the genetic code, known as point mutations, occur. Point mutations that alter the resulting protein sequences are called nonsynonymous mutations, while those that do not alter protein sequences are called silent or synonymous mutations.

Between one-quarter and one-third of point mutations in protein-coding DNA sequences are synonymous. Ever since the genetic code was cracked, those mutations have generally been assumed to be neutral, or nearly so.

But in a study scheduled for online publication June 8 in the journal Nature that involved the genetic manipulation of yeast cells in the laboratory, University of Michigan biologists show that most synonymous mutations are strongly harmful.

The strong nonneutrality of most synonymous mutations -- if found to be true for other genes and in other organisms -- would have major implications for the study of human disease mechanisms, population and conservation biology, and evolutionary biology, according to the study authors.

"Since the genetic code was solved in the 1960s, synonymous mutations have been generally thought to be benign. We now show that this belief is false," said study senior author Jianzhi "George" Zhang, the Marshall W. Nirenberg Collegiate Professor in the U-M Department of Ecology and Evolutionary Biology.

"Because many biological conclusions rely on the presumption that synonymous mutations are neutral, its invalidation has broad implications. For example, synonymous mutations are generally ignored in the study of disease-causing mutations, but they might be an underappreciated and common mechanism."

In the past decade, anecdotal evidence has suggested that some synonymous mutations are nonneutral. Zhang and his colleagues wanted to know if such cases are the exception or the rule.

They chose to address this question in budding yeast (Saccharomyces cerevisiae) because the organism's short generation time (about 80 minutes) and small size allowed them to measure the effects of a large number of synonymous mutations relatively quickly, precisely and conveniently.

They used CRISPR/Cas9 genome editing to construct more than 8,000 mutant yeast strains, each carrying a synonymous, nonsynonymous or nonsense mutation in one of 21 genes the researchers targeted.

Then they quantified the "fitness" of each mutant strain by measuring how quickly it reproduced relative to the nonmutant strain. Darwinian fitness, simply put, refers to the number of offspring an individual has. In this case, measuring the reproductive rates of the yeast strains showed whether the mutations were beneficial, harmful or neutral.

To their surprise, the researchers found that 75.9% of synonymous mutations were significantly deleterious, while 1.3% were significantly beneficial.

"The previous anecdotes of nonneutral synonymous mutations turned out to be the tip of the iceberg," said study lead author Xukang Shen, a graduate student research assistant in Zhang's lab.

"We also studied the mechanisms through which synonymous mutations affect fitness and found that at least one reason is that both synonymous and nonsynonymous mutations alter the gene-expression level, and the extent of this expression effect predicts the fitness effect."

Zhang said the researchers knew beforehand, based on the anecdotal reports, that some synonymous mutations would likely turn out to be nonneutral.

"But we were shocked by the large number of such mutations," he said. "Our results imply that synonymous mutations are nearly as important as nonsynonymous mutations in causing disease and call for strengthened effort in predicting and identifying pathogenic synonymous mutations."

The U-M-led team said that while there is no particular reason why their results would be restricted to yeast, confirmations in diverse organisms are required to verify the generality of their findings.

The other authors of the Nature study are Siliang Song of the U-M Department of Ecology and Evolutionary Biology and Chuan Li of Stanford University. The work was supported by a U.S. National Institutes of Health grant to Zhang.

Journal Reference:

1. Xukang Shen, Siliang Song, Chuan Li & Jianzhi Zhang. Synonymous mutations in representative yeast genes are mostly strongly nonneutral. Nature, 2022 DOI: 10.1038/s41586-022-04823-w 

Courtesy:

University of Michigan. "Most 'silent' genetic mutations are harmful, not neutral -- a finding with broad implications." ScienceDaily. ScienceDaily, 8 June 2022. <www.sciencedaily.com/releases/2022/06/220608112504.htm>.

 

Epigenetic markers predict complications in patients with type 2 diabetes

A new study by researchers at Lund University in Sweden supports the notion that patients with type 2 diabetes patient should be divided into subgroups and given individualised treatment. The study demonstrates that there are distinct epigenetic differences between different groups of patients with type 2 diabetes. The epigenetic markers are also associated with different risks of developing common complications in type 2 diabetes, such as stroke, heart attack and kidney disease.

"We show that there are distinct epigenetic differences between subgroups of patients with type 2 diabetes. The epigenetic markers are associated with different risks of developing common complications in diabetes, such as heart attack, stroke, and kidney disease," says Charlotte Ling, professor of diabetes and epigenetics at Lund University and lead author of the study, published in Diabetes Care.

An acclaimed study by researchers at Lund University, published in 2018, demonstrated that it is possible to divide type 1 diabetes and type 2 diabetes into five subgroups. In November 2021, the same authors published a new study which highlighted genetic differences between the four subgroups of type 2 diabetes, suggesting different causes of the disease.

The latest study shows that there are also epigenetic differences between the four subgroups with type 2 diabetes. The epigenetic markers can be developed to predict common complications of type 2 diabetes, which would allow for tailored treatments of patients.

"Many patients with type 2 diabetes patients are offered standard treatments by the health care system, but growing evidence suggests that these patients need tailored treatments. Our new study adds to the evidence base that it is clinically relevant to classify patients with type 2 diabetes into subgroups to allow for more personalised treatments," says Charlotte Ling, who leads a research group in diabetes and epigenetics at Lund University.

The new study encompasses 533 individuals recently diagnosed with type 2 diabetes from two population-based cohorts in Sweden. The authors measured DNA methylations in the blood at 800,000 sites in the genome of all participants. DNA methylation is a chemical process through which methyl groups attach to the DNA molecule, affecting the function of genes. The researchers found that the four subgroups had different levels of DNA methylation at 4.465 sites.

The findings were used to develop epigenetic risk scores to predict common complications of type 2 diabetes. Epigenetic markers associated with two of the subgroups could predict an increased risk of developing heart attack, stroke, and kidney disease.

"Heart attack and stroke are responsible for most deaths among patients with type 2 diabetes. Kidney disease causes a lot of suffering and is very costly for society, as many patients need dialysis treatment. An epigenetic biomarker that can predict complications at an early stage would make preventive actions possible," says Charlotte Ling.

The authors will need to verify their results in other population-based cohorts. They are also planning to study DNA methylation in tissues from, for example, muscle, adipose tissue, liver, and the pancreas of the four subgroups with type 2 diabetes.

Journal Reference:

1. Silja Schrader, Alexander Perfilyev, Emma Ahlqvist, Leif Groop, Allan Vaag, Mats Martinell, Sonia García-Calzón, Charlotte Ling. Novel Subgroups of Type 2 Diabetes Display Different Epigenetic Patterns, Which Associate With Future Diabetic Complications. Diabetes Care, 2022; DOI: 10.2337/dc21-2489 

Courtesy:

Lund University. "Epigenetic markers predict complications in patients with type 2 diabetes." ScienceDaily. ScienceDaily, 25 May 2022. <www.sciencedaily.com/releases/2022/05/220525102934.htm>.

 

Alcohol may be more risky to the heart than previously thought

 Levels of alcohol consumption currently considered safe by some countries are linked with development of heart failure, according to research presented at Heart Failure 2022, a scientific congress of the European Society of Cardiology (ESC).

"This study adds to the body of evidence that a more cautious approach to alcohol consumption is needed," said study author Dr. Bethany Wong of St. Vincent's University Hospital, Dublin, Ireland. "To minimise the risk of alcohol causing harm to the heart, if you don't drink, don't start. If you do drink, limit your weekly consumption to less than one bottle of wine or less than three-and-a-half 500 ml cans of 4.5% beer."

According to the World Health Organization, the European Union is the heaviest-drinking region in the world.² While it is well recognised that long-term heavy alcohol use can cause a type of heart failure called alcoholic cardiomyopathy,³ evidence from Asian populations suggests that lower amounts may also be detrimental.^4,5 "As there are genetic and environmental differences between Asian and European populations this study investigated if there was a similar relationship between alcohol and cardiac changes in Europeans at risk of heart failure or with pre-heart failure," said Dr. Wong. "The mainstay of treatment for this group is management of risk factors such as alcohol, so knowledge about safe levels is crucial."

This was a secondary analysis of the STOP-HF trial.⁶ The study included 744 adults over 40 years of age either at risk of developing heart failure due to risk factors (e.g. high blood pressure, diabetes, obesity) or with pre-heart failure (risk factors and heart abnormalities but no symptoms).⁷ The average age was 66.5 years and 53% were women. The study excluded former drinkers and heart failure patients with symptoms (e.g. shortness of breath, tiredness, reduced ability to exercise, swollen ankles). Heart function was measured with echocardiography at baseline and follow up.

The study used the Irish definition of one standard drink (i.e. one unit), which is 10 grams of alcohol.⁸ Participants were categorised according to their weekly alcohol intake: 1) none; 2) low (less than seven units; up to one 750 ml bottle of 12.5% wine or three-and-a-half 500 ml cans of 4.5% beer); 3) moderate (7-14 units; up to two bottles of 12.5% wine or seven 500 mL cans of 4.5% beer); 4) high (above 14 units; more than two bottles of 12.5% wine or seven 500 ml cans of 4.5% beer).

The researchers analysed the association between alcohol use and heart health over a median of 5.4 years. The results were reported separately for the at-risk and pre-heart failure groups. In the at-risk group, worsening heart health was defined as progression to pre-heart failure or to symptomatic heart failure. For the pre-heart failure group, worsening heart health was defined as deterioration in the squeezing or relaxation functions of the heart or progression to symptomatic heart failure. The analyses were adjusted for factors that can affect heart structure including age, gender, obesity, high blood pressure, diabetes, and vascular disease.

A total of 201 (27%) patients reported no alcohol usage, while 356 (48%) were low users and 187 (25%) had moderate or high intake. Compared to the low intake group, those with moderate or high use were younger, more likely to be male, and had a higher body mass index.

In the pre-heart failure group, compared with no alcohol use, moderate or high intake was associated with a 4.5-fold increased risk of worsening heart health. The relationship was also observed when moderate and high levels were analysed separately. In the at-risk group, there was no association between moderate or high alcohol use with progression to pre-heart failure or to symptomatic heart failure. No protective associations were found for low alcohol intake.

Dr. Wong said: "Our study suggests that drinking more than 70 g of alcohol per week is associated with worsening pre-heart failure or progression to symptomatic heart failure in Europeans. We did not observe any benefits of low alcohol usage. Our results indicate that countries should advocate lower limits of safe alcohol intake in pre-heart failure patients. In Ireland, for example, those at risk of heart failure or with pre-heart failure are advised to restrict weekly alcohol intake to 11 units for women and 17 units for men. This limit for men is more than twice the amount we found to be safe. More research is needed in Caucasian populations to align results and reduce the mixed messages that clinicians, patients and the public are currently getting."

Notes

¹The abstract 'Moderate alcohol consumption is associated with progression of left ventricular dysfunction in a European stage B heart failure population' will be presented during the session 'Heart failure is a complex syndrome: look at comorbidities' which takes place on 22 May at 09:40 CEST at Moderated ePoster 1.

²World Health Organization data and statistics: https://www.euro.who.int/en/health-topics/disease-prevention/alcohol-use/data-and-statistics.

³Piano MR. Alcoholic cardiomyopathy: incidence, clinical characteristics, and pathophysiology. Chest. 2002;121:1638-1650.

⁴Hung CL, Goncalves A, Lai YJ, et al. Light to moderate habitual alcohol consumption is associated with subclinical ventricular and left atrial mechanical dysfunction in an asymptomatic population: dose-response and propensity analysis. J Am Soc Echocardiogr. 2016;29:1043-1051.e4.

⁵Park SK, Moon K, Ryoo JH, et al. The association between alcohol consumption and left ventricular diastolic function and geometry change in general Korean population. Eur Heart J Cardiovasc Imaging. 2018;19:271-278.

⁶STOP-HF: St Vincent's Screening TO-Prevent Heart Failure.

⁷Bozkurt B, Coats AJS, Tsutsui H, et al. Universal definition and classification of heart failure. J Cardiac Fail. 2021;27:387-413.

⁸The definition of a standard drink varies by country. In the UK, for example, one unit contains eight grams of alcohol.

Citation:

European Society of Cardiology. "Alcohol may be more risky to the heart than previously thought." ScienceDaily. ScienceDaily, 23 May 2022. <www.sciencedaily.com/releases/2022/05/220523135032.htm>.

Artificial cilia could someday power diagnostic devices

Cilia are the body's diligent ushers. These microscopic hairs, which move fluid by rhythmic beating, are responsible for pushing cerebrospinal fluid in your brain, clearing the phlegm and dirt from your lungs, and keeping other organs and tissues clean.

A technical marvel, cilia have proved difficult to reproduce in engineering applications, especially at the microscale.

Cornell researchers have now designed a micro-sized artificial cilial system using platinum-based components that can control the movement of fluids at such a scale. The technology could someday enable low-cost, portable diagnostic devices for testing blood samples, manipulating cells or assisting in microfabrication processes.

The group's paper, "Cilia Metasurfaces for Electronically Programmable Microfluidic Manipulation," published May 25 in Nature. The lead author is doctoral student Wei Wang.

"There are lots of ways to make artificial cilia that respond to light, magnetic or electrostatic forces," Wang said. "But we are the first to use our new nano actuator to demonstrate artificial cilia that are individually controlled."

The project, led by the paper's senior author, Itai Cohen, professor of physics in the College of Arts and Sciences, builds off a platinum-based, electrically-powered actuator -- the part of the device that moves -- his group previously created to enable microscopic robots to walk. The mechanics of those bending bot legs is similar, but the cilia system's function and applications are different, and quite flexible.

"What we're showing here," Cohen said, "is that once you can individually address these cilia, you can manipulate the flows in any way you want. You can create multiple separate trajectories, you can create circular flow, you can create transport, or flows that split up into two paths and then recombine. You can get flow lines in three dimensions. Anything is possible."

"It's been very hard to use existing platforms to create cilia that are small, work in water, are electrically addressable and can be integrated with interesting electronics," Cohen said. "This system solves these problems. And with this kind of platform, we're hoping to develop the next wave of microfluid manipulation devices."

A typical device consists of a chip that contains 16 square units with 8 cilia arrays per unit, and 8 cilia per array, with each cilium about 50 micrometers long, resulting in a "carpet" of about a thousand artificial cilia. As the voltage on each cilium oscillates, its surface oxidizes and reduces periodically, which makes the cilium bend back and forth, allowing it to pump fluid at tens of microns per second. Different arrays can be activated independently, therefore creating an endless combination of flow patterns mimicing the flexibility observed in their biological counterparts.

As a bonus, the team created a cilia device that is equipped with a complementary metal-oxide-semiconductor (CMOS) clock circuit -- essentially an electronic "brain" that allows the cilia to operate without being tethered to a conventional computer system. That opens the door to developing a host of low-cost diagnostic tests that could be performed in the field.

"You can imagine in the future, people taking this tiny centimeter-by-centimeter device, putting a drop of blood on it and conducting all the assays," Cohen said. "You wouldn't have to have a fancy pump, you wouldn't have to have any equipment, you would just literally put it under sunlight and it would work. It could cost on the order of $1 to $10."

Co-authors include postdoctoral researchers Qingkun Liu and Michael Reynolds; former postdoctoral researchers Alejandro Cortese, Ph.D. '19 and Marc Miskin; Michael Cao '14 , Ph.D. '20; David Muller, the Samuel B. Eckert Professor of Engineering; Alyosha Molnar, associate professor of electrical and computer engineering; Paul McEuen, the John A. Newman Professor of Physical Science; and Ivan Tanasijevic and Eric Lauga of the University of Cambridge.

The research was primarily supported by the Army Research Office, the National Science Foundation, the Cornell Center for Materials Research, which is supported by the NSF's MRSEC program, the Air Force Office of Scientific Research and the Kavli Institute at Cornell for Nanoscale Science.

The work was performed in part at the Cornell NanoScale Science and Technology Facility.

 

Journal Reference:

1. Wei Wang, Qingkun Liu, Ivan Tanasijevic, Michael F. Reynolds, Alejandro J. Cortese, Marc Z. Miskin, Michael C. Cao, David A. Muller, Alyosha C. Molnar, Eric Lauga, Paul L. McEuen, Itai Cohen. Cilia metasurfaces for electronically programmable microfluidic manipulation. Nature, 2022; 605 (7911): 681 DOI: 10.1038/s41586-022-04645-w

Cornell University. "Artificial cilia could someday power diagnostic devices." ScienceDaily. ScienceDaily, 25 May 2022. <www.sciencedaily.com/releases/2022/05/220525131206.htm>.