Publisher Health

The blood-brain barrier is impermeable to cholesterol, yet high blood cholesterol is associated with increased risk of Alzheimer’s disease and vascular dementia. However, the underlying mechanisms mediating this relationship are poorly understood. A study published in the open-access journal PLOS Medicine by Vijay Varma and colleagues at the National Institute on Aging, part of the National Institutes of Health, in Baltimore, Maryland, suggests that disturbances in the conversion of cholesterol to bile acids (called cholesterol catabolism) may play a role in the development of dementia.
Little is known about how high blood cholesterol may lead to an increased risk of Alzheimer’s and dementia, yet understanding the underlying processes may lay the foundation for discovering effective therapeutics. To investigate whether abnormalities in cholesterol catabolism through its conversion to bile acids is associated with development of dementia, researchers drew on more than 1800 participants from two prospective studies: the Baltimore Longitudinal Study of Aging (BLSA) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI).
First, the research team investigated whether cholesterol catabolism was associated with brain abnormalities typical of Alzheimer’s and vascular dementia. They next tested whether exposure to cholesterol medications that block bile acid absorption into the bloodstream was associated with an increased risk of dementia among more than 26,000 patients from general practice clinics in the United Kingdom. Finally, they examined 29 autopsy samples from the BLSA to determine whether people with Alzheimer’s disease tend to have altered levels of bile acids in their brains.
The authors found that the risk of vascular dementia increased for males, but not females, with greater number of prescriptions of bile acid blocking drugs. Their findings suggest that cholesterol catabolism and bile acid synthesis may impact dementia progression through sex-specific effects on brain signaling pathways. However, additional studies are needed as the research was limited by the relatively small numbers of autopsy samples. In addition, experimental studies are required to better understand the role of cholesterol breakdown in dementia.
“To further extend these findings, we are now testing whether approved drugs for other diseases that may correct bile acid signaling abnormalities in the brain could be novel treatments for Alzheimer’s disease and related dementias,” said senior author Madhav Thambisetty, M.D., Ph.D., investigator and chief of the Unit of Clinical and Translational Neuroscience in the NIA’s Laboratory of Behavioral Neuroscience. “These analyses are being pursued in the Drug Repurposing for Effective Alzheimer’s Medicines (DREAM) study.”
Story Source:
Materials provided by PLOS. Note: Content may be edited for style and length.

A groundbreaking clinical trial shows we can reduce biological age (as measured by the Horvath 2013 DNAmAge clock) by more than three years in only eight weeks with diet and lifestyle through balancing DNA methylation.
A first-of-its-kind, peer-reviewed study provides scientific evidence that lifestyle and diet changes can deliver immediate and rapid reduction of our biological age. Since aging is the primary driver of chronic disease, this reduction has the power to help us live better, longer.
The study, released on April 12, utilized a randomized controlled clinical trial conducted among 43 healthy adult males between the ages of 50-72. The 8-week treatment program included diet, sleep, exercise and relaxation guidance, and supplemental probiotics and phytonutrients, resulting in a statistically significant reduction of biological age — over three years younger, compared to controls.
The study was independently conducted by the Helfgott Research Institute, with laboratory assistance from Yale University Center for Genome Analysis, and the results independently analyzed at McGill University and the National University of Natural Medicine.
The study’s lead author, Kara Fitzgerald ND IFMCP, stated that “the combined intervention program was designed to target a specific biological mechanism called DNA methylation, and in particular the DNA methylation patterns that have been identified as highly predictive of biological age. We suspect that this focus was the reason for its remarkable impact. These early results appear to be consistent with, and greatly extend, the very few existing studies that have so far examined the potential for biological age reversal. And it is unique in its use of a safe, non-pharmaceutical dietary and lifestyle program, control group, and the extent of the age reduction. We are currently enrolling participants for a larger study which we expect will corroborate these findings.”
Leading epigeneticist Moshe Szyf PhD of McGill University and co-author on the study adds, “The uniqueness of Dr Fitzgerald approach is that her trial devised a natural but mechanistic driven strategy to target the methylation system of our body. This study provides the first insight into the possibility of using natural alterations to target epigenetic processes and improve our well being and perhaps even longevity and lifespan.”
DNA methylation patterns have become a leading means by which scientists evaluate and track biological aging, a term used to describe the accumulation of damage and loss of function to our cells, tissues and organs. This damage is what drives diseases of aging. “What is extremely exciting,” commented Dr. Fitzgerald, “is that food and lifestyle practices, including specific nutrients and food compounds known to selectively alter DNA methylation, are able to have such an impact on those DNA methylation patterns we know predict aging and age-related disease. I believe that this, together with new possibilities for us all to measure and track our DNA methylation age, will provide significant new opportunities for both scientists and consumers.”
Story Source:
Materials provided by Impact Journals LLC. Note: Content may be edited for style and length.

Aging published “Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial” which reported on a randomized controlled clinical trial conducted among 43 healthy adult males between the ages of 50-72. The 8-week treatment program included diet, sleep, exercise and relaxation guidance, and supplemental probiotics and phytonutrients.
Genome-wide DNA methylation analysis was conducted on saliva samples using the Illumina Methylation Epic Array and DNAmAge was calculated using the online Horvath DNAmAge clock (also published in Aging).
The diet and lifestyle treatment was associated with a 3.23 years decrease in DNAmAge compared with controls.
DNAmAge of those in the treatment group decreased by an average 1.96 years by the end of the program compared to the same individuals at the beginning with a strong trend towards significance.
This randomized controlled study, published in Aging, suggests that specific diet and lifestyle interventions may reverse Horvath DNAmAge epigenetic aging in healthy adult males.
The study’s lead author, Kara Fitzgerald ND IFMCP, from The Institute for Functional Medicine said, “Advanced age is the largest risk factor for impaired mental and physical function and many non-communicable diseases including cancer, neurodegeneration, type 2 diabetes, and cardiovascular disease.”
Methylation clocks are based on systematic methylation changes with age.
DNAmAge clock specifically demonstrates about 60% of CpG sites losing methylation with age and 40% gaining methylation.
Almost a quarter of the DNAmAge CpG sites are located in glucocorticoid response elements, pointing to a likely relationship between stress and accelerated aging. Cumulative lifetime stress has been shown to be associated with accelerated aging of the methylome.
Other findings include that PTSD contributes to accelerated methylation age; and that greater infant distress is associated with an underdeveloped, younger epigenetic age.
This is to say the authors have tentatively accepted the hypothesis that the methylation pattern from which the DNAmAge clock is computed is a driver of aging, thus they expect that attempting to directly influence the DNA methylome using diet and lifestyle to set back DNAmAge will lead to a healthier, more “youthful” metabolism.
The Fitzgerald Research Team concluded in their Aging Research Output, “it may be that emerging ‘omics’ approaches continue to evolve our understanding of biological age prediction and reversal beyond DNA methylation alone. Integration of our future understanding of multi-omics data should therefore be considered in the future trials of candidate age-delaying interventions.”
Story Source:
Materials provided by Impact Journals LLC. Note: Content may be edited for style and length.

New estimates suggest that mass gatherings during an election in the Malaysian state of Sabah directly caused 70 percent of COVID-19 cases detected in Sabah after the election, and indirectly caused 64.4 percent of cases elsewhere in Malaysia. Jue Tao Lim of the National University of Singapore, Kenwin Maung of the University of Rochester, New York, and colleagues present these findings in the open-access journal PLOS Computational Biology.
Mass gatherings of people pose high risks of spreading COVID-19. However, it is difficult to accurately estimate the direct and indirect effects of such events on increased case counts.
To address this difficulty, Lim, Maung, and colleagues developed a new computational method for estimating both direct and spill-over effects of mass gatherings. Departing from traditional epidemiological approaches, they employed a statistical strategy known as a synthetic control method, which enabled comparison between the aftermath of mass gatherings and what might have happened if the gatherings had not occurred.
The researchers then applied this method to the Sabah state election. This election involved mandated in-person voting and political rallies, both of which resulted in a significant increase in inter-state travel and in-person gatherings by voters, politicians, and campaign workers. Prior to the election, Malaysia had experienced an average of about 16 newly diagnosed COVID-19 cases per day for nearly four months. After the election, that number jumped to 190 cases per day for 17 days until lockdown policies were reinstated.
Using their novel method, the researchers estimated that mass gatherings during the election directly caused 70 percent of COVID-19 cases in Sabah during the 17 days after the election, amounting to a total of 2,979 cases. Meanwhile, 64.4 percent of post-election cases elsewhere in Malaysia — 1,741 cases total — were indirectly attributed to the election.
“Our work underscores the serious risk that mass gatherings in a single region could spill over into other regions and cause a national-scale outbreak,” Lim says.
Lim and colleagues say that the same synthetic control framework could be applied to death rates and genetic data to deepen understanding of the impact of the Sabah election.
Story Source:
Materials provided by PLOS. Note: Content may be edited for style and length.

As the owner of a human body, you’re carrying trillions of microbes with you everywhere you go. These microscopic organisms aren’t just hitching a ride; many of them perform essential chemical reactions that regulate everything from our digestion to our immune system to our moods.
One important set of reactions relates to fat absorption via bile acids. Our livers make these acids to help digest fats and fat-soluble vitamins as they travel through the small intestine. Near the end of the small intestine, microbes convert the acids into new forms, which can either be beneficial or harmful.
New research from the University of Illinois identifies the last in a set of microbial genes involved in these conversions.
“Locating these bacterial genes will allow mechanistic studies to determine the effect of bile acid conversion on host health. If we find this is a beneficial reaction, therapeutic strategies can be developed to encourage production of these bile acids in the gastrointestinal tract,” says Jason Ridlon, associate professor in the Department of Animal Sciences at U of I and corresponding author of a new article in Gut Microbes.
Microbes produce enzymes that flip the orientation of three hydroxyl groups on bile acid molecules. Flipping them into different configurations rearranges the acid molecules into forms that can be harmful or beneficial. Ridlon and other scientists had already identified the genes for two of these enzymes, but one was still unknown.
To find the missing gene, Ridlon and his collaborators looked back in time. Previous research links the flipping of a specific hydroxyl group — one attached to a location on the acid molecule known as carbon-12 — with a microbe called Clostridium paraputrificum.

In the perpetual arms races between bacteria and human-made antibiotics, there is a new tool to give human medicine the edge, in part by revealing bacterial weaknesses and potentially by leading to more targeted or new treatments for bacterial infections.
A research team led by scientists at The University of Texas at Austin has developed chemical probes to help identify an enzyme, produced by some types of E. coli and pneumococcal bacteria, known to break down several common types of antibiotics, making these bacteria dangerously resistant to treatment.
“In response to antibiotic treatment, bacteria have evolved various mechanisms to resist that treatment, and one of those is to make enzymes that basically chew up the antibiotics before they can do their job,” said Emily Que, assistant professor of chemistry and one of the leading researchers on the team. “The type of tool we developed gives us critical information that could keep us one step ahead of deadly bacteria.”
In a paper published online yesterday in the Journal of the American Chemical Society, the researchers zeroed in on the threat posed by the bacterial enzyme called New Delhi metallo-beta-lactamase (NDM). They set out to create a molecule that glows when it comes into contact with the NDM enzyme. When these chemical probes are added to a test tube, they bind to the enzyme and glow. Such a tool could be used to alert doctors to what kind of bacterial threat is affecting their patients and tell them which antibiotics to use.
NDM breaks down antibiotics in the penicillin, cephalosporin and carbapenem classes, which are some of the safest and most effective treatments for bacterial infections. Other classes of antibiotics exist, but they may carry more side effects, have more drug interactions and may be less available in some parts of the world.
In addition to indicating the presence of the NDM enzyme, the florescent chemical probe developed by Que and Walt Fast, a professor of chemical biology and medicinal chemistry, may help find a different way to combat these resistant bacteria. One treatment option that doctors use with resistant bacteria is to combine common antibiotics and an inhibitor. Although there is no known clinically effective inhibitor for NDM-producing bacteria, Que’s probe could help find one.
Once the probe has bound to the enzyme and begun to glow, if an effective inhibitor is introduced, it will knock the probe loose and the glow would stop. This allows scientists to test a high volume of potential drugs very quickly — research Que and Fast hope to continue in the future.
“This allows us to work towards developing therapies and eventually understanding evolutionary characteristics of such proteins,” said Radhika Mehta, a recent UT Austin doctoral graduate and lead author on the paper. Mehta is currently a postdoctoral fellow in the Merchant Lab at the University of California, Berkeley.
The study also examined a process called nutritional immunity, which comes from the human body’s production of proteins in response to an infection. The proteins snatch up all the available metals in the body, such as the zinc required to make NDM, rendering the bacteria more susceptible to attack.
“The evolution of this bacteria since its discovery in 2008 indicates that not only is it developing antibiotic resistance, it’s attempting to combat this natural human immune process. That’s particularly scary,” Que said.
Que’s probe can also be used to study nutritional immunity and NDM because it will glow only in the presence of the zinc needed to form the enzyme.
Story Source:
Materials provided by University of Texas at Austin. Note: Content may be edited for style and length.

About 12,000 bacteria and viruses collected in a sampling from public transit systems and hospitals around the world from 2015 to 2017 had never before been identified, according to a study by the International MetaSUB Consortium, a global effort at tracking microbes that is led by Weill Cornell Medicine investigators.
For the study, published May 26 in Cell, international investigators collected nearly 5,000 samples over a three-year period across 60 cities in 32 countries and six continents. The investigators analyzed the samples using a genomic sequencing technique called shotgun sequencing to detect the presence of various microbes, including bacteria, archaea (single-celled organisms that are distinct from bacteria), and viruses that use DNA as their genetic material. (Other types of viruses that use RNA as their genetic material, such as SARS-CoV-2, the virus that causes COVID-19, would not have been detected with the DNA analysis methods used in this pre-pandemic study.)
This field of research has important implications for detecting outbreaks of both known and unknown infections and for studying the prevalence of antibiotic-resistant microbes in different urban environments.
“Every time you sit down in the subway, you are likely commuting with an entirely new species,” said senior author Dr. Christopher Mason, co-director of the WorldQuant Initiative for Quantitative Prediction and a professor of physiology and biophysics at Weill Cornell Medicine. Dr. Mason is also co-founder and a paid consultant of Biotia and Onegevity Health, and a paid speaker for WorldQuant LLC.
The current study led to the discovery of 10,928 viruses and 748 bacteria that are not present in any reference databases.
Dr. Mason founded MetaSUB (short for Metagenomics and Metadesign of Subways and Urban Biomes) in 2015, along with Dr. Evan Afshin, who was then an undergraduate student at Macaulay Honors College at Queens College and is now a clinical fellow in physiology and biophysics at Weill Cornell Medicine and a paid consultant for Onegevity Health. The newly released study was led by Drs. Mason, David Danko, a Weill Cornell Graduate School doctoral student in Dr. Mason’s lab during the study, and Daniela Bezdan, who was a research associate in computational biomedicine at Weill Cornell Medicine at that time.

Crohn’s disease, a type of inflammatory bowel disease (IBD) that causes inflammation (pain and swelling) in the gastrointestinal tract, can cause daily health problems, frequent hospitalizations and surgery when not adequately controlled. While there is no cure for Crohn’s disease, there are treatments that can help patients live a symptom-free life.
After a detailed review of available literature, the American Gastroenterological Association (AGA) has released new clinical guidelines outlining the benefits and risks of each drug currently available to Crohn’s patients. Based on this research, AGA recommends the early introduction of biologics for patients experiencing luminal and fistulizing Crohn’s disease rather than waiting until other treatments fail. These guidelines are published in Gastroenterology, AGA’s official journal.
“With many new drugs entering the market, clinician’s ability to treat patients with Crohn’s disease has improved greatly over the last 20 years,” said lead author Joseph D. Feuerstein, MD, from Beth Israel Deaconess, Boston, Massachusetts. “We hope this new guideline serves as a manual for clinicians in selecting the right therapies for their patients, which should lead to improved patient outcomes and less need for invasive surgery.”
Key guideline recommendations:1. Biologics are the most effective drugs for the management of Crohn’s and they should be used early, rather than delaying their use until after failure of mesalamine and/or corticosteroids, in patients with moderate to severe or fistulizing Crohn’s disease. These drugs are antibodies and can more precisely target the immune system which is causing the inflammation in Crohn’s disease. a. Anti-tumor necrosis factor (anti-TNF) agents or ustekinumab are recommended and vedolizumab is suggested as a first-line treatment. b. In patients who have previously not responded to anti-TNF agents, AGA recommends ustekinumab or vedolizumab. c. The biologic natalizumab is no longer recommended due to potential adverse events and the availability of safer treatment options.
Story Source:
Materials provided by American Gastroenterological Association. Note: Content may be edited for style and length.

Current neural network algorithms produce impressive results that help solve an incredible number of problems. However, the electronic devices used to run these algorithms still require too much processing power. These artificial intelligence (AI) systems simply cannot compete with an actual brain when it comes to processing sensory information or interactions with the environment in real time.
Neuromorphic chip detects high-frequency oscillations
Neuromorphic engineering is a promising new approach that bridges the gap between artificial and natural intelligence. An interdisciplinary research team at the University of Zurich, the ETH Zurich, and the UniversityHospital Zurich has used this approach to develop a chip based on neuromorphic technology that reliably and accurately recognizes complex biosignals. The scientists were able to use this technology to successfully detect previously recorded high-frequency oscillations (HFOs). These specific waves, measured using an intracranial electroencephalogram (iEEG), have proven to be promising biomarkers for identifying the brain tissue that causes epileptic seizures.
Complex, compact and energy efficient
The researchers first designed an algorithm that detects HFOs by simulating the brain’s natural neural network: a tiny so-called spiking neural network (SNN). The second step involved imple-menting the SNN in a fingernail-sized piece of hardware that receives neural signals by means of electrodes and which, unlike conventional computers, is massively energy efficient. This makes calculations with a very high temporal resolution possible, without relying on the internet or cloud computing. “Our design allows us to recognize spatiotemporal patterns in biological signals in real time,” says Giacomo Indiveri, professor at the Institute for Neuroinformatics of UZH and ETH Zur-ich.
Measuring HFOs in operating theaters and outside of hospitals
The researchers are now planning to use their findings to create an electronic system that reliably recognizes and monitors HFOs in real time. When used as an additional diagnostic tool in operating theaters, the system could improve the outcome of neurosurgical interventions.
However, this is not the only field where HFO recognition can play an important role. The team’s long-term target is to develop a device for monitoring epilepsy that could be used outside of the hospital and that would make it possible to analyze signals from a large number of electrodes over several weeks or months. “We want to integrate low-energy, wireless data communications in the design — to connect it to a cellphone, for example,” says Indiveri. Johannes Sarnthein, a neurophysiologist at UniversityHospital Zurich, elaborates: “A portable or implantable chip such as this could identify periods with a higher or lower rate of incidence of seizures, which would enable us to deliver personalized medicine.” This research on epilepsy is being conducted at the Zurich Center of Epileptology and Epilepsy Surgery, which is run as part of a partnership between UniversityHospital Zurich, the Swiss Epilepsy Clinic and the University Children’s Hospital Zurich.
Story Source:
Materials provided by University of Zurich. Note: Content may be edited for style and length.