Publisher Health

If humans are ever going to be able to regrow damaged tissues the way lizards and fish routinely do, it will require the precise control of gene expression in time and place — otherwise you might end up with random cells growing everywhere or a new body part that never quits growing. That is, stopping the process just as important as starting it.
A team of Duke scientists studying how other animals regrow damaged tissues has made an important step toward controlling at least one part of the regenerative machinery with that kind of precision. They used the mechanisms zebrafish rely on to repair damage to their hearts combined with viral vectors used for gene therapy in humans.
In a new paper appearing online Dec. 13 in Cell Stem Cell, the researchers demonstrate the ability to control gene activity in response to injury, limiting it to a specific region of tissue and during a defined time window, rather than being continuously active in the entire organ.
They borrowed a segment of fish DNA that they call a TREE, tissue regeneration enhancer element. TREEs are a family of gene enhancers included in the genome that are responsible for sensing an injury and orchestrating the activity of repair-related genes for reconstruction in a specific place. These enhancers also can shut off gene activity as healing is completed. These regulatory elements have been found in fruit flies, worms, and mice as well as the zebrafish.
“We probably have them too,” said Ken Poss, Ph.D, the James B. Duke Distinguished Professor of Regenerative Biology in the Duke School of Medicine, who discovered heart regeneration in zebrafish two decades ago and has been studying it since. “But it’s just easier for us to find them in zebrafish and ask if they work in mammals.”
About 1,000 nucleotides long, these enhancer sequences are bristling with recognition sites for different factors and stimuli to attach and change gene activity. “We don’t fully understand how they do this and what they’re truly responding to,” Poss said.

Atrial and ventricular fibrillations are dangerous heart arrhythmias that claim millions of lives each year. Current treatment for them is a high-energy defibrillation shock that can be intensely painful and lead to further heart damage. New work applying principles from nonlinear dynamics looks to find ways to reset the heart with fewer side effects.
With numerical simulations, researchers from the Max Planck Institute for Dynamics and Self-Organization, German Center for Cardiovascular Research, Georg-August-Universitӓt Gӧttingen, and University Medical Center Gӧttingen have demonstrated a new way to time weak electrical pulses that can stop certain life-threatening arrhythmias. Publishing their work in Chaos, by AIP Publishing, the group shows that timed pulses are successful in ending atrial and ventricular fibrillations.
The study provides early evidence that one theorized approach to controlling fibrillations — adaptive deceleration pacing — can improve the performance of defibrillators.
“In numerical simulations, we investigate how the dynamics of chaotic electrical excitation waves, which govern the dynamics of the heart during fibrillations, can be controlled more efficiently,” said author Thomas Lilienkamp. “Our goal is to use numerical simulations to find control strategies that avoid the application of high-energy shocks and that can also be tested in experimental setups and eventually on patients to reduce side effects.”
Adaptive deceleration pacing uses a series of weak pulses that are spaced farther apart over time to respond to the heart and return it to a normal rhythm in a few beats.
“With our approach, we can develop a pulse sequence specifically designed for a specific patient and even for a specific arrhythmia,” Lilienkamp said. “This can be crucial, since even two arrhythmias in the same patient can be different in terms of the underlying dynamics characterized.”
After starting a chaotic spiral wave form that is characteristic of the arrhythmias in four different heart models, the authors tested their approach using different pulse pacing sequences. The high-dimensional complexity of the dynamics and its dependence on control parameters makes numerical simulations a useful tool for handling such a high volume of calculations.
“In order to investigate and compare the performance of different pulse sequences, a large number of numerical simulations is required. The success rate we use as a benchmark for a specific pulse sequence is a statistical quantity averaged over the result of many single simulations,” Lilienkamp said.
Adapting the rate of deceleration to the spectrum of electrical signal frequencies in the simulated cardiac tissue significantly increased the success rate of stopping arrhythmias with relatively weak pulses. To boot, the adaptive deceleration pacing doesn’t require a sophisticated set of control parameters, showing promise for use in future defibrillators.
The group hopes to continue its work in more complex models and in experimental setups with real cardiac tissue.
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Materials provided by American Institute of Physics. Note: Content may be edited for style and length.

Oral cancer is the 13th most common type of cancer globally, and oral squamous cell carcinomas (OSCCs) account for more than 90% of oral cancers. An estimated 300,000 new cases and 145,000 deaths worldwide were attributed to oral cancer in 2012.
Since oral cancer occurs in one of the most accessible sites in the body, it can be easily treated if detected promptly. If caught early in the disease state, oral cancers that remain localized and are 2 centimeters or smaller can be cured and five-year survival rates exceed 90%.
In Journal of Vacuum Science & Technology B, copublished by AIP Publishing and AVS, researchers from the University of Florida and National Yang Ming Chiao Tung University in Taiwan report a breakthrough hand-held biosensor that enables quick and accurate detection of oral cancer.
“Oral squamous cell carcinomas are one of the most common lip and oral cavity cancer types,” said Minghan Xian, co-author and a researcher at the University of Florida. “It requires early detection via various medical technologies to improve the survival rate. While most detection techniques for OSCC require histological testing in a lab to confirm the presence of cancer and cancer type, a point-of-care detection technique is preferred for on-site use and a quick result readout.”
The group’s biosensor consists of a sensor strip, similar to a glucose strip, and a circuit board (a hand-held terminal like a glucometer) for detection.
“Typically, test fluid is introduced into a small liquid channel on the tip of the sensor strips,” said Xian. “A few electrodes sit within the liquid channel, and the surface of these electrodes contain antibodies to specific proteins present within human oral cancer lesions. Short electrode pulses get sent through these electrodes during detection, and then the circuit board module analyzes this signal and outputs a four-digit number that correlates to its concentration.”
As far as applications, there’s tremendous interest within the sensor and medical communities to develop semiconductor- and electrochemical-based biomarker detection. The team is now looking forward to demonstrating their integrated solution for cancer and other disease detection via a hand-held point-of-care device with a short detection time and low detection limit. They also hope their work will inspire further research into this topic.
“The next step in this continuum is to conduct the analysis using in vivo samples of CIP2A — a biomarker of OSCC — in oral cancer and non-oral cancer patients with biopsy as a gold standard,” said Xian.
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Materials provided by American Institute of Physics. Note: Content may be edited for style and length.

The reason your three-pound brain doesn’t feel heavy is because it floats in a reservoir of cerebrospinal fluid (CSF), which flows in and around your brain and spinal cord. This liquid barrier between your brain and skull protects it from a hit to your head and bathes your brain in nutrients.
But the CSF has another critical, if less known, function: it also provides immune protection to the brain. Yet, this function hasn’t been well studied.
A Northwestern Medicine study of CSF has discovered its role in cognitive impairment, such as Alzheimer’s disease. This discovery provides a new clue to the process of neurodegeneration, said study lead author David Gate, assistant professor of neurology at Northwestern University Feinberg School of Medicine.
The study will be published Dec. 13 in Cell.
The study found that, as people age, their CSF immune system becomes dysregulated. In people with cognitive impairment, such as those with Alzheimer’s disease, the CSF immune system is drastically different from healthy individuals, the study also discovered.
“We now have a glimpse into the brain’s immune system with healthy aging and neurodegeneration,” Gate said. “This immune reservoir could potentially be used to treat inflammation of the brain or be used as a diagnostic to determine the level of brain inflammation in individuals with dementia.”
“We provide a thorough analysis of this important immunologic reservoir of the healthy and diseased brain,” Gate said. His team is sharing the data publicly, and its results can be searched online.

Strong neighborhood connections reduced the negative impact of living alone on the death rates of older Chinese Americans, according to Rutgers researchers.
The study, published in Social Science and Medicine, examined if neighborhood cohesion in Chinese Americans living in the greater Chicago area would reduce the impact of living alone on early death.
“Older Chinese Americans who lived by themselves in neighborhoods with low cohesion were much more likely to die earlier than those who lived by themselves in neighborhoods with strong cohesion,” said Yanping Jiang, author of the study and faculty member at the Center for Population Behavioral Health at Rutgers Institute for Health, Health Care Policy and Aging Research.
In the United States, about 27 percent of people ages 60 and older live alone, according to Pew Research Center. Living alone has been found to be associated with various poor health outcomes, such as depression, cardiovascular disease, dementia, poor biological health and premature death. Therefore, researchers found it important to identify which factors may help mitigate the negative effects of living alone.
Using data from the Population Study of Chinese Elderly in Chicago (PINE), the researchers examined whether the perception of trust and connection among neighbors had an impact on the risk of death in this population. They found participants who lived alone and reported low interaction or connection with their neighbors had a 48.5 percent increased risk of death than their peers living with others, whereas participants who lived alone and reported strong cohesion with their neighborhood had a similar risk of death compared to those living with others.
With a clearer understanding of how different types of neighborhoods can affect the health of individuals, social policies and public health initiatives can be improved to create better neighborhood environments for promoting health of older adults, researchers said.
“Our findings show the particular challenges faced by older adults who live alone in communities with little interaction or connection,” said Jiang, who is an instructor at the Rutgers Department of Family Medicine and Community Health. “Enhancing neighborhood cohesion may be a promising way to reduce early death for older adults who live alone.”
Researchers encourage future studies to examine other factors involved in neighborhoods and how they influence the health of older adults. Additionally, the public also can play a role in improving community health by reaching out and being kind to neighbors, particularly those who live alone.
Coauthors of the study include Mengting Li of Renmin University of China and Tammy Chung of Rutgers Institute for Health, Health Care Policy and Aging Research. Research was supported by the Rutgers-NYU Center for Asian Health Promotion and Equity and the National Institute on Aging.
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Materials provided by Rutgers University. Original written by Nicole Swenarton. Note: Content may be edited for style and length.

Researchers from the University of Birmingham, UK, who identified a novel mechanism for platelet activation in pathogenic blood clotting (thrombosis) are now turning their attention to sepsis.
Identified by Associate Professor Julie Rayes and Dr Martina Colicchia from the Birmingham Platelet Group, and described in a recent paper in Blood, this previously unknown axis comprises platelet receptor glycoprotein I alpha (GPIb?), and an anti-microbial protein S100A8/A9, which is released from activated immune cells.
The mechanism is not blocked by classical anti-platelet drugs currently used to treat arterial thrombosis, and is distinct from the well-described ‘clotting cascade’ that limits blood loss following injury.
Dr Rayes explains: “When clots are formed at the site of a vascular injury, two main populations of platelet are seen. Highly activated and aggregated platelets are located at the core of the clot, while procoagulant platelets are present at the shell around the core and support the generation of fibrin which stabilizes the clot.
“The S100A8/A9-GPIb? axis does not induce platelet aggregation but it does induce the formation of procoagulant platelets and accelerates fibrin activation and thrombosis. This axis might be more relevant in disease states where the activation of innate immune cells and platelets play a pivotal role in clotting.”
High levels of S100A8/A9 are seen in the blood in thrombo-inflammatory diseases including myocardial infarction (MI), deep vein thrombosis (DVT) and infections such as COVID-19 and sepsis, and their presence correlates with thrombotic complications, and worse outcomes for patients.
The researchers believe this novel mechanism may be relevant in thrombosis observed under chronic inflammatory conditions and acute infections and believe that the interaction of S100A8/A9 with multiple receptors* makes it an interesting target to limit both clotting and inflammation during sepsis.
Dr Rayes said: “Thrombosis is a major complication during infection, so drugs are needed that target pathogenic clotting while maintaining vascular integrity and normal clotting process (haemostasis). By selectively targeting S100A8/A9, we aim to target a key pathogenic inflammatory and thrombotic molecule to limit both inflammation and thrombosis during infection.”
Associate Professor Rayes presented at the 63rd American Society of Hematology (ASH) Annual Meeting on Monday December 12, 2022 (16.30-18.05 CST). She expects to publish the results of the sepsis study in 2023.
University of Birmingham Enterprise has filed a patent application covering the targeting of the S100A8/A9-GPIb? axis in the treatment and prevention of thrombosis in chronic inflammatory and thrombotic diseases and is now seeking partners for commercial development or licensing.
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Materials provided by University of Birmingham. Note: Content may be edited for style and length.

New research led by scientists at the University of Colorado Boulder suggests that eyes may really be the window to the soul — or, at least, how humans dart their eyes may reveal valuable information about how they make decisions.
The new findings offer researchers a rare opportunity in neuroscience: the chance to observe the inner workings of the human brain from the outside. Doctors could also potentially use the results to, one day, screen their patients for illnesses like depression or Parkinson’s Disease.
“Eye movements are incredibly interesting to study,” said Colin Korbisch, doctoral student in the Paul M. Rady Department of Mechanical Engineering at CU Boulder and lead author of the study. “Unlike your arms or legs, the speed of eye movements is almost totally involuntary. It’s a much more direct measurement of these unconscious processes happening in your brain.”
He and his colleagues, including researchers at Johns Hopkins University in Baltimore, published their findings in November in the journal Current Biology.
In the study, the team asked 22 human subjects to walk on a treadmill then choose between different settings displayed on a computer screen: a brief walk up a steep grade or a longer walk on flat ground.
Researchers discovered that the subjects’ eyes gave them away: Even before they made their choices, the treadmill users tended to move their eyes faster when they looked toward the options they ended up choosing. The more vigorously their eyes moved, the more they seemed to prefer their choice.

The prevalence of type 2 diabetes is projected to continue rising and one in three Singaporeans currently has a risk of developing diabetes in their lifetime. Several early-life cardiometabolic complications make identifying high-risk populations and application of diabetes preventive strategies paramount.
Among the high-risk groups are women who experienced diabetes during pregnancy, commonly known as gestational diabetes mellitus or gestational diabetes. Compared to the general healthy female population, these women may face a ten-fold higher risk of developing type 2 diabetes.
Current known research has found that, instead of artificially- and sugar-sweetened drinks, drinking two to five cups of either caffeinated or decaffeinated coffee a day is potentially a healthier substitute in delaying the onset or preventing type 2 diabetes.
This is likely due to the bioactive components in coffee, such as polyphenols, which are naturally-occurring plant micronutrients. Bioactive components are types of chemicals found in small amounts in plants and certain foods, such as fruits, vegetables, nuts, oils, and whole grains, and may promote good health.
This common and popular drink appears to reduce the risk of type 2 diabetes in the general population. However, whether it may also be beneficial among women who had gestational diabetes remained unknown.
To investigate this, Professor Cuilin Zhang, Director of the Global Centre for Asian Women’s Health (GloW) and a professor in the Department of Obstetrics and Gynecology at the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), with her team at GloW, in collaboration with the Harvard T.H. Chan School of Public Health and the National Institutes of Health (NIH), examined the roles of long-term coffee consumption after the complicated pregnancy and subsequent risk of type 2 diabetes among women with a history of gestational diabetes.

With an emphasis on fruits, vegetables and legumes, the Mediterranean diet has long been applauded for its multiple health benefits. Now, new research shows that it may also help overcome infertility, making it a non-intrusive and affordable strategy for couples trying to conceive.
Conducted by Monash University, the University of the Sunshine Coast, and the University of South Australia, the review found that the Mediterranean diet can improve fertility, assisted reproductive technology (ART) success, and sperm quality in men.
Specifically, researchers identified that the anti-inflammatory properties of a Mediterranean diet can improve couples’ chances of conception.
Infertility is a global health concern affecting 48 million couples and 186 million individuals worldwide.
UniSA researcher, Dr Evangeline Mantzioris, says modifying preconception nutrition is a non-invasive and potentially effective means for improving fertility outcomes.
“Deciding to have a baby is one of life’s biggest decisions, but if things don’t go as planned, it can be very stressful for both partners,” Dr Mantzioris says.

Females’ propensity to deposit more fat in places like their hips, buttocks and the backs of their arms, so-called subcutaneous fat, is protective against brain inflammation, which can result in problems like dementia and stroke, at least until menopause, scientists report.
Males of essentially any age have a greater propensity to deposit fat around the major organs in their abdominal cavity, called visceral adiposity, which is known to be far more inflammatory. And, before females reach menopause, males are considered at much higher risk for inflammation-related problems from heart attack to stroke.
“When people think about protection in women, their first thought is estrogen,” says Alexis M. Stranahan, PhD, neuroscientist in the Department of Neuroscience and Regenerative Medicine at the Medical College of Georgia at Augusta University. “But we need to get beyond the kind of simplistic idea that every sex difference involves hormone differences and hormone exposure. We need to really think more deeply about the underlying mechanisms for sex differences so that we can treat them and acknowledge the role that sex plays in different clinical outcomes.”
Diet and genetics are other likely factors that explain the differences broadly assigned to estrogen, says Stranahan, corresponding author of a study in the American Diabetes Association journal Diabetes.
She acknowledges that the findings are potentially heretical and revolutionary and certainly surprising even to her. “We did these experiments to try and nail down, first of all, what happens first, the hormone perturbation, the inflammation or the brain changes.”
To learn more about how the brain becomes inflamed, they looked at increases in the amount and location of fat tissue as well as levels of sex hormones and brain inflammation in male and female mice at different time intervals as they grew fatter on a high-fat diet.