Genetic risk of heart disease may be due to low Omega 3-linked biomarker

People who are genetically more likely to suffer from cardiovascular diseases may benefit from boosting a biomarker found in fish oils, a new study suggests.
In a genetic study in 1,886 Asian Indians published in PLOS ONE today (Wednesday 12 May), scientists have identified the first evidence for the role of adiponectin, an obesity-related biomarker, in the association between a genetic variation called omentin and cardiometabolic health.
The team, led by Professor Vimal Karani from the University of Reading, observed that the role of adiponectin was linked to cardiovascular disease markers that were independent of common and central obesity among the Asian Indian population.
Prof Vimal Karani, Professor of Nutrigenetics and Nutrigenomics at the University of Reading said:
“This is an important insight into one way that people who are not obese may develop heart disease, through low concentrations of a biomarker in the body called adiponectin. It may also demonstrate why certain lifestyle factors such as consumption of oily fish and regular exercise are so important for warding off the risk of heart disease.
“We studied Asian Indian populations who have a particular genetic risk of developing heart disease and did see that the majority of our participants were already cardiometabolically unhealthy. However, the omentin genetic variation that we studied is prevalent across diverse ethnic groups and warrants further work to see whether omentin is playing a role in heart disease risk in other groups too.”
The Asian Indian population who took part in the study were found to have a significant association between low levels of adiponectin and cardiovascular disease, even after adjusting for factors normally linked with heart disease.
Participants in the study were screened and assessed based on a range of cardiovascular measures including BMI, fasting blood sugar and cholesterol, and more than 80% of those who took part being assessed as cardiometabolically unhealthy.
Further analysis showed that those with genetic variation in omentin production also had less of the biomarker adiponectin in their body.
Professor Vimal Karani said:
“What we can see clearly from the observations is that there is a three-stage process going on where the omentin gene difference is contributing to the low biomarker adiponectin, which in turn seems to be linked to worse outcomes and risk of heart disease.
“The omentin gene itself works to produce a protein in the body that has been shown to have anti-inflammatory and cardioprotective effects, and variations in the omentin gene have previously linked to cardiometabolic diseases. The findings suggests that people can develop cardiometabolic diseases due to this specific omentin genetic risk, if they have low levels the biomarker adiponectin.”
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All gas, no brakes: Testosterone may act as 'brake pedal' on immune response

Autoimmune diseases have something in common with horses, bachelor’s degrees and daily flossing habits: women are more likely to have them.
One reason for autoimmune diseases’ prevalence in women may be sex-based differences in inflammation. In a new study, West Virginia University researcher Jonathan Busada investigated how sex hormones affect stomach inflammation in males and females. He found that androgens — or male sex hormones — may help to keep stomach inflammation in check.
“Stomach cancer is primarily caused by rampant inflammation,” said Busada, an assistant professor in the School of Medicine and researcher with the Cancer Institute. “The overarching theme of my lab is to understand what’s controlling the balance between a protective immune response, which is just targeting the infection, and a pathogenic immune response, which is like a toddler throwing a temper tantrum and damaging everything. It looks like androgens may be really important in tipping that balance toward a protective response.”
His findings appear in Gastroenterology.
Busada’s study focused on testosterone, the primary male sex hormone.
The study also considered glucocorticoids — steroid hormones that the adrenal glands secrete. Unlike testosterone, glucocorticoids are not sex hormones. Their production doesn’t differ substantially between women and men.

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Peptide could allow medical marijuana to relieve pain without side effects

Many people live with chronic pain, and in some cases, cannabis can provide relief. But the drug also can significantly impact memory and other cognitive functions. Now, researchers reporting in ACS’ Journal of Medicinal Chemistry have developed a peptide that, in mice, ∆9-tetrahydrocannabinol (THC), the main component of Cannabis sativa, to fight pain without the side effects.
According to the U.S. Centers for Disease Control and Prevention, about 20% of adults in the U.S. experienced chronic pain in 2019. Opioids, the mainstay for severe pain management, are effective, but patients can easily become addicted to them. In some studies, medical marijuana has been helpful in relieving pain from migraines, neuropathy, cancer and other conditions, but the side effects present hurdles for widespread therapeutic use. Previously, researchers identified two peptides that disrupt an interaction between a receptor that’s the target of THC and another receptor that binds serotonin, a neurotransmitter that regulates learning, memory and other cognitive functions. When the researchers injected the peptides into the brains of mice, the mice had fewer memory problems caused by THC. Now, this team, led by Rafael Maldonado, David Andreu and colleagues, wanted to improve these peptides to make them smaller, more stable, orally active and able to cross the blood-brain barrier.
Based on data from molecular dynamic simulations, the researchers designed two peptides that were less than half the length of the original ones but preserved their receptor binding and other functions. They also optimized the peptide sequences for improved cell entry, stability and ability to cross the blood-brain barrier. Then, the researchers gave the most promising peptide to mice orally, along with a THC injection, and tested the mice’s pain threshold and memory. Mice treated with both THC and the optimized peptide reaped the pain-relieving benefits of THC and also showed improved memory compared with mice treated with THC alone. Importantly, multiple treatments with the peptide did not evoke an immune response. These findings suggest that the optimized peptide is an ideal drug candidate for reducing cognitive side effects from cannabis-based pain management, the researchers say.
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AI helps predict treatment outcomes for patients with diseased dental implants

Peri-implantitis, a condition where tissue and bone around dental implants becomes infected, besets roughly one-quarter of dental implant patients, and currently there’s no reliable way to assess how patients will respond to treatment of this condition.
To that end, a team led by the University of Michigan School of Dentistry developed a machine learning algorithm, a form of artificial intelligence, to assess an individual patient’s risk of regenerative outcomes after surgical treatments of peri-implantitis.
The algorithm is called FARDEEP, which stands for Fast and Robust Deconvolution of Expression Profiles. In the study, researchers used FARDEEP to analyze tissue samples from a group of patients with peri-implantitis who were receiving reconstructive therapy. They quantified the abundance of harmful bacteria and certain infection fighting immune cells in each sample.
Patients who were at low risk for periodontal disease showed more immune cells that were highly adept at controlling bacterial infections, said Yu Leo Lei, senior author and assistant professor of dentistry.
The team was surprised that the types of cells associated with better outcomes for implant patients challenge conventional thinking, said Lei, who also has an appointment at the Rogel Cancer Center.
“Much emphasis has been placed on the immune cell types that are more adept at wound healing and tissue repair,” he said. “However, here we show that immune cell types that are central to microbial control are strongly correlated with superior clinical outcomes.
“Surgical management can reduce bacterial burdens across all patients, however, only the patients with more immune cell subtypes for bacterial control can suppress the recolonization of pathogenic bacteria and show better regenerative outcomes.”
Dental implant-supported crowns offer esthetic, functional and natural-feeling tooth replacements, and the market is estimated to reach $6.8 billion by 2024. Dental implants have transformed reconstructive options, but the emerging endemic of peri-implantitis has severely compromised the long-term success of implant dentistry, the researchers said.
Peri-implantitis can lead to progressive bone loss, bleeding, pus and eventual loss of the dental implants and associated crowns or dentures that they support. Replacement of a new dental implant at the previously damaged site is often challenging because of poor bone quality and delayed healing. Preventive implant maintenance and long-term management of peri-implantitis becomes part of the routine practice after implant reconstruction.
“Regenerative therapy for peri-implantitis is expensive and treatment outcomes are unpredictable,” said first author Jeff Wang, U-M clinical assistant professor and principal investigator for the regenerative treatment of peri-implantitis clinical trial. “It would be very helpful if we could use the information to determine the best course of treatment, or maybe we’d decide that the more sensible option would be to replace an old implant with a new one, despite the challenge to rebuild the bone.”
In the future, it may be possible to predict the risk of peri-implantitis before a dental implant is placed, he said. More human clinical trials are required before FARDEEP is ready to be used widely by clinicians.
“However, this proof-of-concept study offers a personalized approach to identify the types of patients that better respond to regenerative therapies,” said co-author William Giannobile, a professor of oral medicine, infection and immunity, and dean of the Harvard School of Dental Medicine. Previously, Giannobile was at the U-M School of Dentistry.
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Brain computer interface turns mental handwriting into text on screen

Scientists are exploring a number of ways for people with disabilities to communicate with their thoughts. The newest and fastest turns back to a vintage means for expressing oneself: handwriting.
For the first time, researchers have deciphered the brain activity associated with trying to write letters by hand. Working with a participant with paralysis who has sensors implanted in his brain, the team used an algorithm to identify letters as he attempted to write them. Then, the system displayed the text on a screen — in real time.
The innovation could, with further development, let people with paralysis rapidly type without using their hands, says study coauthor Krishna Shenoy, a Howard Hughes Medical Institute Investigator at Stanford University who jointly supervised the work with Jaimie Henderson, a Stanford neurosurgeon.
By attempting handwriting, the study participant typed 90 characters per minute — more than double the previous record for typing with such a “brain-computer interface,” Shenoy and his colleagues report in the journal Nature on May 12, 2021.
This technology and others like it have the potential to help people with all sorts of disabilities, says Jose Carmena, a neural engineer at the University of California, Berkeley, who was not involved in the study. Though the findings are preliminary, he says, “it’s a big advancement in the field.”
Brain-computer interfaces convert thought into action, Carmena says. “This paper is a perfect example: the interface decodes the thought of writing and produces the action.”
Thought-powered communication

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Ancient gut microbiomes may offer clues to modern diseases

Scientists are rapidly gathering evidence that variants of gut microbiomes, the collections of bacteria and other microbes in our digestive systems, may play harmful roles in diabetes and other diseases. Now Joslin Diabetes Center scientists have found dramatic differences between gut microbiomes from ancient North American peoples and modern microbiomes, offering new evidence on how these microbes may evolve with different diets.
The scientists analyzed microbial DNA found in indigenous human paleofeces (desiccated excrement) from unusually dry caves in Utah and northern Mexico with extremely high levels of genomic sequencing, says Joslin Assistant Investigator Aleksandar Kostic, PhD, senior author of a Nature paper presenting the work.
Performing genomic analysis more broadly and deeply than previous studies on ancient human gut microbiomes, the study was the first to reveal novel species of microbes in the specimens, says Kostic, who is also an Assistant Professor of Microbiology at Harvard Medical School.
In previous studies of children in Finland and Russia, Kostic and his colleagues showed that children in industrialized regions, who were much more likely to develop type 1 diabetes than those in non-industrialized areas, also had very different gut microbiomes. “We were able to identify specific microbes and microbial products that we believe hampered a proper immune education in early life,” Kostic says. “And this leads later on to higher incidents of not just type 1 diabetes, but other autoimmune and allergic diseases.”
So what would a healthy human microbiome look like before the effects of industrialization? “I’m convinced that you can’t answer that question with any modern living people,” says Kostic, who points that even tribes in extremely remote regions of the Amazon are contracting Covid-19.
Steven LeBlanc, an archeologist formerly with Harvard’s Peabody Museum of Archaeology and Ethnology, came to Kostic with a dramatic alternative source: microbial DNA found in human paleofeces samples that museums have collected from arid environments in the North American Southwest.

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An anesthetic may affect tau spread in the brain to promote Alzheimer's disease pathology

During the development and progression of Alzheimer’s disease, a protein called tau accumulates and spreads in the brain. Understanding the mechanisms behind tau spread — and its consequences — may point to new prevention and treatment strategies for Alzheimer’s disease and other forms of dementia. New insights now come from research that was led by investigators at Massachusetts General Hospital (MGH) and involves an anesthetic known to affect cognitive function. The findings are published in Communications Biology.
The scientists note that inflammation plays an important role in Alzheimer’s disease, and microglia — immune cells that reside in the brain — are thought to be involved in this process by producing an inflammatory molecule called interleukin-6. To see if tau stimulates microglia to drive the development of Alzheimer’s disease pathology, the MGH investigators and their colleagues conducted experiments with an inhaled anesthetic called sevoflurane. Their previous work showed that sevoflurane can cause a change (specifically, phosphorylation, or the addition of phosphate) to tau that leads to cognitive impairment in mice. Other researchers have also found that sevoflurane and certain other anesthetics may affect cognitive function.
In this current study, the team developed a novel method to measure tau levels, called nanobeam-sensor technology. “The nanobeam sensor is ultrasensitive, requires a small volume, and can measure low concentrations of molecules, including tau and phosphorylated tau,” says co-lead author Feng Liang, MD, PhD, an instructor in the Department of Anesthesia, Critical Care and Pain Medicine (DACCPM) at MGH.
The group conducted experiments in mice and cells and discovered that sevoflurane causes tau to leave neurons and enter microglia, where it stimulates the cells’ production of interleukin-6, which in turn leads to inflammation and cognitive impairment. The trafficking of tau from neurons to microglia involves tau phosphorylation and membrane-bound carriers called extracellular vesicles that are released from cells.
“These data demonstrate anesthesia-associated tau spreading and its consequences,” says senior author Zhongcong Xie, MD, PhD, director of the Geriatric Anesthesia Research Unit in the DACCPM. “This tau spreading could be prevented by inhibitors of tau phosphorylation or extracellular vesicle generation.”
Sevoflurane did not increase the release of lactate dehydrogenase, a molecule with a similar size and weight as tau, from neurons. “This finding indicates that neuronal cell membranes and cell viability were not compromised by sevoflurane treatment and that the sevoflurane-induced leaking of tau was not a passive process,” says co-lead author Yuanlin Dong, MD, a research fellow in the department.
Another inhaled anesthetic called desflurane did not have the same effects as sevoflurane. “Our results suggest that the anesthetics sevoflurane and desflurane may have different impacts on tau phosphorylation and tau spreading. More important, sevoflurane may be used as a clinically relevant tool to study tau spreading and its underlying mechanisms,” says Xie. “We hope this work will lead to more research on anesthesia, tau proteins, and Alzheimer’s disease pathology that will ultimately improve care for patients.”
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Rapid COVID-19 diagnostic test delivers results within 4 minutes with 90 percent accuracy

A low-cost, rapid diagnostic test for COVID-19 developed by Penn Medicine provides COVID-19 results within four minutes with 90 percent accuracy. A paper published this week in Matter details the fast and inexpensive diagnostic test, called RAPID 1.0 (Real-time Accurate Portable Impedimetric Detection prototype 1.0). Compared to existing methods for COVID-19 detection, RAPID is inexpensive and highly scalable, allowing the production of millions of units per week.
Despite the urgency of the pandemic, most available methods for COVID-19 testing use RT-PCR — reverse transcription polymerase chain reaction — to detect SARS-CoV-2. Though effective, the technique requires large laboratory space and trained workers to employ. These tests are also costly, they run a risk of cross-contamination, and can take hours or days to provide results.
RAPID was developed by a team led by César de la Fuente, PhD, a Presidential Assistant Professor in Psychiatry, Microbiology, Chemical and Biomolecular Engineering, and Bioengineering, to quickly and accurately detect the virus while remaining cheap enough to be widely accessible. An electrode printed using a screen printer — thousands of which can be printed in a day at very low cost — can detect the virus in nasal swab or saliva samples. The results can be read on a benchtop instrument or on a smartphone.
“Prior to the pandemic, our lab was working on diagnostics for bacterial infections. But then, COVID-19 hit. We felt a responsibility to use our expertise to help — and the diagnostic space was ripe for improvements,” de la Fuente said. “We feel strongly about the health inequities witnessed during the pandemic, with testing access and the vaccine rollout, for example. We believe inexpensive diagnostic tests like RAPID could help bridge some of those gaps.”
The RAPID technology uses electrochemical impedance spectroscopy (EIS), which transforms the binding event between the SARS-CoV-2 viral spike protein and its receptor in the human body, the protein ACE2 (which provides the entry point for the coronavirus to hook into and infect human cells), into an electrical signal that clinicians and technicians can detect. That signal allows the test to discriminate between infected and healthy human samples. The signal can be read through a desktop instrument or a smartphone.
The team assessed the performance of RAPID using both COVID-19 positive and negative clinical samples from the Hospital of the University of Pennsylvania, including samples of the highly contagious UK B117 variant. In blinded tests, they analyzed 139 nasal swab samples — 109 of which were COVID-19 positive and 30 COVID-19 negative, as determined by standard RT-PCR clinical assessments. The team also analyzed 50 saliva samples from patients. For the nasal swab samples, RAPID was 87.1 percent accurate. For saliva samples, RAPID was 90 percent accurate.

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Untangling the brain: new research offers hope for Alzheimer's disease

Since the discovery of Alzheimer’s disease over a century ago, two hallmarks of the devastating illness have taken center stage.
The first, known as amyloid plaques, are dense accumulations of misfolded amyloid protein, occurring in the spaces between nerve cells. Most efforts to halt the advance of Alzheimer’s disease have targeted amyloid protein plaques. To date, all have met dispiriting failure.
The second classic trait has, until recently, received less scrutiny. It consists of string-like formations within the bodies of neurons, produced by another crucial protein — tau. These are known as neurofibrillary tangles.
In a new study, researchers with the ASU-Banner Neurodegenerative Disease Center at the Biodesign Institute and their colleagues investigate these tangles in the brain — pathologies not only characteristic of Alzheimer’s but other neurodegenerative conditions as well.
The research homes in on a particular protein known as Rbbp7, whose dysregulation appears linked to the eventual formation of tau protein tangles and the rampant cell death associated with Alzheimer’s and other neurodegenerative diseases.
“We had a hunch that this protein was involved in Alzheimer’s disease, particularly because we know that the protein was decreased in Alzheimer’s disease post-mortem brain tissue when compared with normal brains,” says Nikhil Dave, lead author of the new study.

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Certain gut microbiota profile can predict mortality

The study conducted by the University of Turku and the Finnish Institute for Health and Welfare together with an international research team is so far the largest population-level study in the world examining the connection between human gut microbiota and health and mortality in the following decades.
The composition of the research subjects’ gut microbiota was analysed from stool samples collected in 2002. The researchers had access to follow-up data on the subjects’ mortality until 2017, i.e., close to the present day.
“Many bacterial strains that are known to be harmful were among the enterobacteria predicting mortality, and our lifestyle choices can have an impact on their amount in the gut. By studying the composition of the gut microbiota, we could improve mortality prediction, even while taking into account other relevant risk factors, such as smoking and obesity. The data used in this research make it possible for the first time to study the long-term health impact of the human gut microbiota on a population level,” says Teemu Niiranen, Professor of Medicine at the University of Turku, Finland.
Everyone has a unique microbiota
Human microbiota is highly individual and consists of a vast amount of different bacteria and other microorganisms. The bacteria predicting a shorter lifespan were discovered when the researchers compared health records and billions of DNA strands retrieved from the research subjects’ microbiota.
“We developed a machine learning algorithm that screened the data for microbial species having a significant association with mortality among the research subjects in the following two decades after the sample was taken,” describes Associate Professor Leo Lahti from the University of Turku.
“Finnish population studies are unique in their extent and scope even on a global scale. With new data science methods, we are now able to study more closely the specific connections between microbiota and, for example,” ageing and incidence of common diseases, Lahti continues.
Even though the connection between gut microbiota and lifestyle has lately been studied extensively in cross-sectional studies, there are only a few long-term follow-up studies available. Therefore, only a small amount of information has been gained about the connection between microbiota and health in the long term.
The study was based on a sample of over 7,000 Finnish adults. The data are part of the FINRISK 2002 study conducted by the Finnish Institute for Health and Welfare.
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