Publisher Health

A previously healthy infant who suffered aborted sudden cardiac death was found to have a de novo genetic mutation in the SOS1 gene. Such mutations are typical of Noonan syndrome and suggests the syndrome may be a cause of unrecognized sudden death in infancy. The case is reported in Heart Rhythm Case Reports, an official journal of the Heart Rhythm Society, published by Elsevier.
Noonan syndrome is a genetic disorder that affects normal development, causing skeletal, cardiac, and neurocognitive delays. The infant had none of the usual structural cardiac findings of Noonan syndrome, such as damaged heart valves or abnormally thick heart muscle tissue. However, they may appear later in development.
“Genetic testing in cases of unexplained aborted or sudden cardiac deaths, even in previously healthy children, can be valuable in establishing a diagnosis, determining the prognosis, and assessing risk to family members,” said co-authors Christopher W. Follansbee, MD, and Lindsey Malloy-Walton, DO, of the Ward Family Heart Center, Children’s Mercy Kansas City and University of Missouri School of Medicine Kansas City, Kansas City, MO, USA.
A two-month-old female infant did not awaken as usual for her morning feeding; her mother found her limp, pale, and suffering from breathing difficulty. EMS arrived quickly and found the infant pulseless. Three shocks from a defibrillator were needed to restore sinus rhythm. On presentation to the ICU, the patient had incessant, rapid episodes of ectopic atrial tachycardia. This potentially serious arrhythmia is an unusual finding in the neonatal postarrest period. Normal cardiac function was restored after medication and treatment. An echocardiogram revealed a structurally normal heart with normal valves, and there was no ventricular hypertrophy, dilation, or noncompaction noted. Other tests were normal.
The genetics team was consulted, and a standard family history was obtained. An older sibling had no known medical conditions. The child’s paternal grandfather had died of a presumed heart attack in his 50s, but no autopsy had been performed. There was no family history of congenital heart disease, sudden death, development delay, or other conditions. A next-generation sequencing panel revealed the likely pathogenetic variant of the SOS1 gene associated with Noonan syndrome.
Noonan syndrome belongs to a family of related genetic syndromes known as RASopathies with overlapping phenotypic features, including skeletal, dermatologic, and neurocognitive findings. Cardiac phenotypes are also common. SOS1-mediated Noonan syndrome can have a mild phenotype, which may not be apparent until the child becomes older, when neurocognitive findings become more noticeable, as seems to be the case with this patient.
“To the extent of our knowledge, our case is the first reported ventricular fibrillation arrest associated with a RASopathy in the absence of the typical structural cardiac phenotypes of hypertrophic cardiomyopathy or pulmonary stenosis. In this patient’s case it will allow for monitoring and early intervention on typical manifestations of Noonan syndrome as the patient grows,” observed Dr. Follansbee and Dr. Malloy-Walton. “Continued research is essential to uncover underlying causes for unrecognized sudden deaths in infants.”
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Materials provided by Elsevier. Note: Content may be edited for style and length.

A team in the Department of Biomedical Engineering, co-led by associate professor Dr. Akhilesh Gaharwar and assistant professor Dr. Abhishek Jain, has designed a 3D-bioprinted model of a blood vessel that mimics its state of health and disease, thus paving the way for possible cardiovascular drug advancements with better precision.
Vascular diseases such as aneurysms, peripheral artery disease and clots inside blood vessels account for 31% of global deaths. Despite this clinical burden, cardiovascular drug advancements have slowed over the past 20 years. The decrease in cardiovascular therapeutic development is attributed to the lack of efficiency in converting possible treatments into approved methods, specifically due to the discrepancy between studies that take place outside the body compared to inside.
The team’s research at Texas A&M University aims to remodel current methodologies to minimize this gap and improve the translatability of these techniques by directing 3D bioprinting toward vascular medicine. Gaharwar is a biomaterials expert and has developed novel bioinks that offer unprecedented biocompatibility and control of mechanical properties needed to print blood vessels, whereas Jain’s expertise lies in creating biomimetic in vitro models of vascular and hematological diseases. This interdisciplinary and collaborative project was recently published in the journal Advanced Healthcare Materials.
Bioprinting in 3D is an advanced manufacturing technique capable of producing unique, tissue-shaped constructs in a layer-by-layer fashion with embedded cells, making the arrangement more likely to mirror the native, multicellular makeup of vascular structures. A range of hydrogel bioinks was introduced to design these structures; however, there is a limitation in available bioinks that can mimic the vascular composition of native tissues. Current bioinks lack high printability and are unable to deposit a high density of living cells into complex 3D architectures, making them less effective.
To overcome these shortcomings, Gaharwar and Jain developed a new nanoengineered bioink to print 3D, anatomically accurate, multicellular blood vessels. Their approach offers improved real-time resolution for both macro-structure and tissue-level micro-structure, something that currently is not possible with available bioinks.
“A remarkably unique characteristic of this nanoengineered bioink is that regardless of cell density, it demonstrates a high printability and ability to protect encapsulated cells against high shear forces in the bioprinting process,” Gaharwar said. “Remarkably, 3D-bioprinted cells maintain a healthy phenotype and remain viable for nearly one month postfabrication.”
Leveraging these unique properties, the nanoengineered bioink is printed into 3D cylindrical blood vessels, consisting of living co-cultures of endothelial cells and vascular smooth muscle cells, which provides researchers the opportunity to model vascular function and disease impact.

Recent research has found that changes in the gut microbiota — the trillions of bacteria and other microbes that live in the intestines — can alter the brain and behavior. Now, a study led by scientists at UCLA could elucidate how and why that phenomenon occurs.
In the experiment, which was conducted with mice, researchers found that gut microbes can exacerbate the effects of cognitive impairment because of how they affect the hippocampus, the region of the brain that is critical for memory and learning. They found that the concentration of one group of bacteria called Bilophila increased dramatically in the gut microbiota of mice fed that were fed a ketogenic diet — high in fat, and low in carbohydrates — and were intermittently deprived of oxygen, creating a condition called hypoxia.
The scientists also found that a ketogenic diet, hypoxia and treatment with a species of Bilophila called Bilophila wadsworthia impaired the hippocampus, leading to reduced cognitive ability in mice.
The research is published in the peer-reviewed journal Cell Host & Microbe.
The researchers gave several mice a ketogenic diet and others a standard diet. Then, all of the mice received reduced levels of oxygen for five consecutive days and then were given four days to recover. Depriving the animals of some oxygen was a way for the scientists to cause cognitive impairment, in order to mimic the cognitive impairment in humans that can be caused by neurological diseases or aging.
Next, the scientists observed their ability to navigate a maze. When trying to find their way out of a maze, mice on the ketogenic diet made an average of 30% more errors than mice given the standard diet. (The range of difference between the two groups was 25% to 75%.)
The researchers also evaluated whether the different diets alone could cause any change in cognitive behavior in mice who had not been deprived of oxygen. In that experiment, there was no appreciable difference in the mice’s ability to find their way out of the maze based on whether they had a ketogenic diet or a standard diet — indicating that the negative impact on cognitive ability only occurred in combination with oxygen deprivation.

The emergence of the delta variant and continued vaccine hesitancy have caused many health and government officials to revisit the need for non-pharmaceutical interventions (NPIs) like social distancing policies, mask wearing, contact tracing and isolating infected individuals to manage new COVID-19 surges.
The one thing everyone wants to avoid is another lockdown, but what intervention measures work best without the need for strict social distancing? New research from the University of Georgia suggests that officials should prioritize contact tracing and quarantine.
“When social distancing in the general population is hard to achieve, we could still rely on contact tracing and case isolation if we do a good job,” said lead author Yang Ge, a doctoral student in the department of epidemiology & biostatistics in UGA’s College of Public Health.
The study, which was recently published in Epidemics, modeled the impact of three interventions — social distancing, contact tracing and case isolation — on containing COVID-19 using both real patient data from China’s Zhejiang province and computer simulations.
The database included over 1,200 symptomatic cases reported between Jan. 7 and Feb. 22, 2020, and the model accounted for their daily contact activities with other people before, during and after the epidemic. As a result, the researchers were able to evaluate the contribution of each intervention, rather than only the combined effect of all three strategies.
They found that the outbreak in Zhejiang was suppressed by isolating cases within five days with 36.5% of infected contacts quarantining. This scenario was only achieved when robust contact tracing was in place.
“Social distancing, case isolation and contact tracing are all critical in suppressing the epidemic, and they interact with each other in the sense that if you fail in one area, the other efforts need to be strengthened. In particular, we noticed that contact tracing is very important despite not being part of the major conversation in current control efforts,” said lead co-author Ye Shen, an associate professor of epidemiology & biostatistics at UGA.
In addition to testing the impact of each intervention, they also modeled scenarios where certain interventions were weaker than others, for example, if it took more or less time to isolate a positive case.
“We found that even with a low prevalence level, a gradual reopening is challenging without further strengthening NPIs,” Shen said. Specifically, the curve was steeper when contact tracing was less efficient.
These findings take on new meaning as areas of the U.S. and elsewhere are seeing major case spikes, while many lower income countries are still waiting on vaccines to arrive and continue to rely on these interventions to keep their citizens safe.
“Slow tracing and delayed isolation could easily increase the outbreak size by tens of folds. We should allocate sufficient resources to support such efforts, for example, funding contact tracing forces, allowing people to work or study from home when exposed to COVID-19 cases, and at the minimum, encourage everyone to wear a face mask indoors,” they said.
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Materials provided by University of Georgia. Original written by Lauren Baggett. Note: Content may be edited for style and length.

An international research team led by scientists from the Hong Kong University of Science and Technology (HKUST) has developed a novel strategy using brain-wide genome-editing technology that can reduce Alzheimer’s disease (AD) pathologies in genetically modified AD mouse models. This advanced technology offers immense potential to be translated as a novel long-acting therapeutic treatment for AD patients.
In China alone, over 500,000 patients are estimated to be living with a hereditary form of AD — familial Alzheimer’s disease (FAD), which is a congenital form of AD highly associated with family history. Although FAD has a clear genetic cause and can be diagnosed before cognitive problems occur, no effective treatment currently exists.
There is enormous potential in the use of genome-editing technology* as therapeutic strategies for diseases caused by inherited mutations, such as FAD. It is especially useful for correcting disease-causing genetic mutations before symptoms appear, for which it is considered a “once-and-for-all” treatment as its effects can last a lifetime. However, several hurdles have prevented its clinical development and application — most notably the lack of an effective, efficient, and non-invasive means to deliver genome-editing agents into the brain. Furthermore, existing genome-editing technologies are unable to generate beneficial outcomes throughout the whole brain.
Recently, a team led by Prof. Nancy Ip, Vice-President for Research and Development at HKUST, developed a new genome-editing system that not only crosses the blood-brain barrier, but also delivers an optimized genome-editing tool to the entire brain. Using a newly engineered delivery vehicle for genome-editing, this strategy achieves efficient brain-wide genome editing through a single non-invasive intravenous administration. This effectively disrupts FAD-inflicted mutations in AD mouse models and ameliorates AD pathologies throughout the entire brain, paving the way to novel therapeutic development for the disease.
Meanwhile, the research team also found in the mouse models that the level of amyloid, a protein thought to drive neurodegeneration in AD, remained low for 6 months post-treatment (about 1/3 of their normal lifespan), demonstrating that this single-shot genome-editing strategy has lasting effects. More importantly, no side effects were detected so far in the mice.
“As the first demonstration of efficient brain-wide genome editing to alleviate Alzheimer’s disease pathology throughout the whole brain, this is really an exciting development,” said Prof. Ip, who is also the Morningside Professor of Life Science and Director of the State Key Laboratory of Molecular Neuroscience at HKUST. “Our work is an important milestone for the use of genome editing in treating hereditary brain diseases, and contributes to the development of precision medicine for inherited forms of neurodegenerative diseases.”
This research was a collaborative effort among scientists from HKUST; the California Institute of Technology; and the Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences. The results were recently published in Nature Biomedical Engineering.
*Genome editing is a technology that precisely modifies a living organism’s genomic DNA by deleting, inserting, or replacing the DNA at specific locations of the genome.
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Materials provided by Hong Kong University of Science and Technology. Note: Content may be edited for style and length.

A survey of more than 17,000 pregnant and lactating individuals who received the COVID-19 vaccine showed that the individuals did not experience symptoms any more severe than their non-pregnant counterparts.
The UW Medicine study, published today in JAMA Network Open, showed “there were not any increased reactions in pregnant individuals beyond what is expected from a vaccine,” said Dr. Linda Eckert, a professor of obstetrics and gynecology at the University of Washington School of Medicine and the study’s senior author.
“Pregnant people do well with the vaccine,” added lead author Dr. Alisa Kachikis.
The findings come a week after the Centers for Diseases Control and Prevention formally recommended that all pregnant women get vaccinated against the virus. The CDC reported that only 23% of U.S. pregnant women were vaccinated as of the end of July. The percentage is even lower among Black and Latina women.
“We hope that this data will be another reassuring piece of information … about why pregnant individuals need to get vaccinated against COVID-19,” Eckert said. “Not only is the vaccine safe, our research shows just how well the vaccine is tolerated in pregnant individuals — which is a common fear I hear from my patients. In contrast, we are continuing to learn more and more about just how dangerous COVID-19 infections are in pregnancy.”
In January 2021, Kachikis set up an online cohort study of women: those who were pregnant or lactating and those who were neither pregnant nor lactating. The women were invited to describe their reactions after receiving at least one dose of a COVID-19 vaccine. By March, 17,525 individuals had responded.

Time-restricted eating (TRE), a dietary regimen that restricts eating to specific hours, has garnered increased attention in weight-loss circles. A new study by Salk scientists further shows that TRE confers multiple health benefits besides weight loss. The study also shows that these benefits may depend on sex and age.
Most TRE studies focus on weight loss in young male mice, but Salk scientists wanted to determine whether TRE confers additional benefits on other populations. Their findings, published in Cell Reports on August 17, 2021, show that while age and sex do affect the outcomes of TRE, the eating strategy delivers multiple health benefits for young and old of both sexes, and indicates that TRE may be a valuable intervention for type 2 diabetes, fatty liver disease and liver cancer, and even infectious diseases such as COVID-19, in humans.
“For many TRE clinical interventions, the primary outcome is weight loss, but we’ve found that TRE is good not only for metabolic disease but also for increased resilience against infectious diseases and insulin resistance,” says Satchidananda Panda, a professor in Salk’s Regulatory Biology Laboratory and holder of the Rita and Richard Atkinson Chair.
Glucose intolerance is the first step on a slippery slope to non-alcoholic fatty liver disease and liver cancer — one of the few cancers whose incidence and death rates have increased, rather than declined, in the past 25 to 30 years. Further, over 40 percent of Americans are already diabetic or prediabetic, with the American Diabetes Association predicting 1.5 million new cases each year. These trends make finding a simple treatment for glucose intolerance a major priority.
Breaking the conventional young-male-mice mold, the researchers fed a high-fat, high-sugar diet to male and female mice of two age groups (equivalent to 20- and 42-year-old humans), restricting eating to nine hours per day. The team ran tests to ascertain how age and sex affect the outcomes of TRE on a variety of health parameters: fatty liver disease; glucose regulation; muscle mass, performance and endurance; and survival of sepsis, a life-threatening response to infection. They also took the rare step of matching their lab conditions to the animals’ circadian clocks (mice sleep during the day and rise at night), often working via night-vision goggles and specialized lighting.
Analyzing the tissues of mice on TRE to ascertain their chemical makeup and processes, the researchers found that regardless of age, sex or weight loss profile, TRE strongly protected against fatty liver disease, a condition that affects up to 100 million Americans and for which no medicine has been approved.

Though hand-washing is proven effective in combating the spread of disease and infection, the physics behind it has rarely been studied. But in Physics of Fluids, by AIP Publishing, researchers from Hammond Consulting Limited describe a simple model that captures the key mechanics of hand-washing.
By simulating hand-washing, they estimated the time scales on which particles, like viruses and bacteria, were removed from hands.
The mathematical model acts in two dimensions, with one wavy surface moving past another wavy surface, and a thin film of liquid between the two. Wavy surfaces represent hands because they are rough on small spatial scales.
Particles are trapped on the rough surfaces of the hand in potential wells. In other words, they are at the bottom of a valley, and in order for them to escape, the energy from the water flow must be high enough to get them up and out of the valley.
The strength of the flowing liquid depends on the speed of the moving hands. A stronger flow removes particles more easily.
“Basically, the flow tells you about the forces on the particles,” said author Paul Hammond. “Then you can work out how the particles move and figure out if they get removed.”
He likens the process to scrubbing a stain on a shirt: the faster the motion, the more likely it is to come out.

Cells translate their genetic material at rapid rates with exquisite precision to reproduce, repair damage or even combat disease. But the process can deregulate and give rise to disease. Byproducts of errant processes can build up like gunk in the gears, especially around neurons, breaking down the repair mechanisms and causing further damage and even neurodegenerative disorders such as Alzheimer’s disease.
Now, an international research team may have found that a protein implicated in tumor growth may be able to help regulate awry cellular translation and protect against neuronal decay. They published their results on July 13 in the Cell Reports.
“Researchers have begun to understand that age-related neurodegenerative diseases may be caused by slow but steady accumulation of toxic peptide products, which leads to death of neurons, such as beta-amyloid plaques causing Alzheimer’s disease,” said lead paper author Katsura Asano, professor in Hiroshima University’s Graduate School of Integrated Sciences for Life and also in Division of Biology, Kansas State University. “Repeat-associated non-AUG (RAN) translation is one of the mechanisms that generates such toxic products.”
When replicating their genetic material, cells look for specifically ordered markers that signal the spot where they should start and end the copy to make a specific protein. The signal is typically “AUG,” but RAN translation doesn’t need this signal and can begin processing at other points. The problem is that RAN translation can end up copying bits of repeated genetic information that become the toxic buildup that leads to neurodegeneration.
“Taking advantage of our knowledge on translation, we examined whether the translational regulatory protein 5MP can suppress RAN translation, which would also suppress the production of the toxic repeat peptide products,” Asano said.
In diseased conditions, 5MP is a protein that can potentially transform a healthy cell into a tumor cell. In healthy conditions, 5MP mimics a protein involved in regulating RAN translation. The researchers used electron microscopy and computer-directed modeling to reveal the structure of the preinitiation complex of molecules that assemble prior to RAN translation beginning. They found that 5MP competes with the protein it mimics in human cells and, when it wins, it reduces RAN translation and its toxic byproducts.
To better understand how this finding translates to disease outcomes, the researchers engineered flies with fragile X-associated tremor ataxia syndrome, a neurodegenerative disorder. They found that increasing the levels of 5MP in the affected flies repressed neuronal toxicity and enhanced their lifespan.
“Taken together, these data suggest that modulation of 5MP levels could be a viable therapeutic target by which to selectively reduce RAN translation in repeat expansion disorders,” Asano said. “More studies on 5MP and the mechanism of translation can greatly contribute to the understanding and care of neurodegenerative diseases.”
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Materials provided by Hiroshima University. Note: Content may be edited for style and length.

The findings, from researchers at Imperial College London and University of South Carolina, add to mounting evidence that inflammation, and the accompanying release of the molecule histamine, affects a key molecule responsible for mood in the brain — serotonin.
If replicated in humans, the findings — which identify histamine as a ‘new molecule of interest’ in depression — could open new avenues for treating depression, which is the most common mental health problem worldwide.
Inflammation — a blanket term describing an immune response — triggers the release of histamine in the body. This increases blood flow to affected areas to flood them with immune cells. While these effects help the body fight infections, both long-term and acute inflammation is increasingly linked to depression. Inflammation accompanies infections but can also be caused by stress, allergic responses and a host of chronic diseases such as diabetes, obesity, cancer and neurodegenerative diseases.
Lead author Dr Parastoo Hashemi, from Imperial’s Department of Bioengineering, said: “Inflammation could play a huge role in depression, and there is already strong evidence that patients with both depression and severe inflammation are the ones most likely not to respond to antidepressants.
“Our work shines a spotlight on histamine as a potential key player in depression. This, and its interactions with the ‘feel-good molecule’ serotonin, may thus be a crucial new avenue in improving serotonin-based treatments for depression.”
Chemical messengers
Serotonin, often referred to as the ‘feel-good molecule’, is a key target for depression-tackling drugs. Commonly prescribed selective serotonin reuptake inhibitors (SSRIs) inhibit the re-absorption of serotonin in the brain, allowing it to circulate for longer and improve mood.