Early lower respiratory tract infections and obstructive sleep apnea in children

Several birth cohorts have defined the pivotal role of early lower respiratory tract infections (LRTI) in the inception of pediatric respiratory conditions. However, the association between early LRTI and the development of obstructive sleep apnea (OSA) in children has not been established.
For the first time, researchers at Children’s National Hospital, have identified the association between early LRTI and the development of OSA in children, according to a study published in the journal, SLEEP. “These results suggest that respiratory syncytial virus LRTI may contribute to the pathophysiology of OSA in children, said Gustavo Nino, M.D., director of sleep medicine at Children’s National.
The study also demonstrated that children with a history of severe RSV bronchiolitis during early infancy had more than two-fold increased odds of developing OSA during the first five years of life independently of other risk factors.
“The results suggest that RSV LRTI may contribute to the pathophysiology of OSA in children, raising concern for the possibility that primary prevention strategies can hinder the initial establishment of OSA following early viral LRTIs,” says Dr. Nino. “Primary prevention of OSA in children would have a dramatic effect in reducing the increasing incidence of this condition and in preventing its detrimental effects on childhood health and beyond.”
The novel findings also raise the possibility that novel anticipatory strategies and interventions can be developed to identify and prevent the initial establishment of OSA following viral respiratory infections during early infancy, providing a dramatic effect in reducing the increasing incidence of this condition and its multiple detrimental effects on childhood health and beyond.
“Our study offers a new paradigm for investigating mechanisms implicated in the early pathogenesis of OSA in the pediatric population, says Dr. Nino.
Marishka Brown, Ph.D., director of the National Center on Sleep Disorders Research at the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH), agreed. “The findings from this study suggest that viral lower respiratory tract infections could predispose to the development of sleep-disordered breathing in later childhood,” Brown said. “More research to determine how these infections affect airway function could lead to a better understanding of how sleep apnea develops in pediatric patients.” This study includes funding support from the NIH, including the NHLBI.
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Materials provided by Children’s National Hospital. Note: Content may be edited for style and length.

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COVID-19 nasal vaccine candidate effective at preventing disease transmission, study shows

Breathe in, breathe out. That’s how easy it is for SARS-CoV-2, the virus that causes COVID-19, to enter your nose. And though remarkable progress has been made in developing intramuscular vaccines against SARS-CoV- 2, such as the readily available Pfizer, Moderna and Johnson & Johnson vaccines, nothing yet — like a nasal vaccine — has been approved to provide mucosal immunity in the nose, the first barrier against the virus before it travels down to the lungs.
But now, we’re one step closer.
Navin Varadarajan, University of Houston M.D. Anderson Professor of Chemical and Biomolecular Engineering, and his colleagues, are reporting in iScience the development of an intranasal subunit vaccine that provides durable local immunity against inhaled pathogens.
“Mucosal vaccination can stimulate both systemic and mucosal immunity and has the advantage of being a non-invasive procedure suitable for immunization of large populations,” said Varadarajan. “However, mucosal vaccination has been hampered by the lack of efficient delivery of the antigen and the need for appropriate adjuvants that can stimulate a robust immune response without toxicity.”
To solve those problems, Varadarajan collaborated with Xinli Liu, associate professor of pharmaceutics at the UH College of Pharmacy, and an expert in nanoparticle delivery. Liu’s team was able to encapsulate the agonist of the stimulator of interferon genes (STING) within liposomal particles to yield the adjuvant named NanoSTING. The function of the adjuvant is to promote the body’s immune response.
“NanoSTING has a small particle size around 100 nanometers which exhibits significantly different physical and chemical properties to the conventional adjuvant,” said Liu.
“We used NanoSTING as the adjuvant for intranasal vaccination and single-cell RNA-sequencing to confirm the nasal-associated lymphoid tissue as an inductive site upon vaccination. Our results show that the candidate vaccine formulation is safe, produces rapid immune responses — within seven days — and elicits comprehensive immunity against SARS-CoV-2,” said Varadarajan.
A fundamental limitation of intramuscular vaccines is that they are not designed to elicit mucosal immunity. As prior work with other respiratory pathogens like influenza has shown, sterilizing immunity to virus re-infection requires adaptive immune responses in the respiratory tract and the lung.
The nasal vaccine will also serve to equitably distribute vaccines worldwide, according to the researchers. It is estimated that first world countries have already secured and vaccinated multiple intramuscular doses for each citizen while billions of people in countries like India, South Africa, and Brazil with large outbreaks are currently unimmunized. These outbreaks and viral spread are known to facilitate viral evolution leading to decreased efficacy of all vaccines.
“Equitable distribution requires vaccines that are stable and that can be shipped easily. As we have shown, each of our components, the protein (lyophilized) and the adjuvant (NanoSTING) are stable for over 11 months and can be stored and shipped without the need for freezing,” said Varadarajan.
Varadarajan is co-founder of AuraVax Therapeutics Inc., a pioneering biotech company developing novel intranasal vaccines and therapies to help patients defeat debilitating diseases, including COVID-19. The company has an exclusive license agreement with UH with respect to the intellectual property covering intranasal vaccines and STING agonist technologies. They have initiated the manufacturing process and plan to engage the FDA later this year.
Along with Liu, Varadarajan’s team includes postdoctoral researchers Xingyue An, Melisa Martinez-Paniagua; research assistants Ali Rezvan, Mohsen Fathi and Sujit Biswas; doctoral student Samiur Rahman Sefat, all from the University of Houston; and Shailbala Sing, postdoctoral researcher at University of Texas M. D. Anderson Cancer Center; Melissa Pourpak, BD; and Cassian Yee, M.D., University of Texas M. D. Anderson Cancer Center.
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Materials provided by University of Houston. Original written by Laurie Fickman. Note: Content may be edited for style and length.

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Pilot study of diet/exercise in young adults with intellectual disabilities is promising

Adhering to a diet and exercise program to manage health can be a challenge for anyone.
But maintaining a healthy weight may present unique challenges for young adults with inherent barriers such as cognitive impairment.
A pilot study at the University of Cincinnati found that young adults with autism spectrum disorder (ASD) and intellectual disabilities (ID) were able to lose or maintain their weight with a system of education and support in place.
“It was a wonderful experience to work with the young adults and see them be empowered to select their health goals,” says the study’s lead author Laura Nabors, PhD, a professor in UC’s School of Human Services in the College of Education, Criminal Justice, and Human Services.
According to the pilot study, research shows that young adults with ASD and ID are at risk for being overweight or obese and may face higher levels of health risks for cardiovascular disease, sleep disorders, gastrointestinal problems and Type 2 diabetes.
Nabors, and a team of UC faculty, undergraduates and graduate students and a disability researcher at Cincinnati Children’s Hospital Medical Center, oversaw a nutrition and exercise instructional program that involved 17 participants and guardians. Over the course of a year, the team and participants met weekly (either in person or online during COVID-19 lockdowns) and were provided lessons on healthy eating and exercise.

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Heterogeneous development of children with Congenital Zika Syndrome-associated microcephaly

At age two, children who were born with neurological abnormalities due to congenital Zika Virus (ZIKV) have a range of neurodevelopmental profiles that can be tracked using a routine neurological assessment, according to a new study published this week in the open-access journal PLOS ONE by Dr. Albert Ko of Yale University, US and Dr. Federico Costa of The Federal University of Bahia, Brazil, and their colleagues.
Children exposed to ZIKV in utero can develop distinct neurological abnormalities, such as microcephaly, and central nervous system malformations. Previous studies have found neurodevelopmental delays of around 20 months in young children with congenital Zika syndrome (CZS)-associated microcephaly. However, cases have also been reported describing babies with normal neurodevelopment despite equivalent presentation with CZS-associated microcephaly at birth.
In the new study, researchers followed 42 CZS-affected children between the ages of 25 and 32 months from a Microcephaly Outpatient Clinic in Brazil. A total of 19 of the enrolled children (45.2%) were male, the median age at evaluation was 28 months, and all children had a head circumference more than 2 standard deviations below average. Participants were evaluated on their neurological and neurodevelopment, using Hammersmith Infant Neurological Examination (HINE) and the Bayley Scales of Infant and Toddler Neurodevelopment (Bayley-III) respectively.
In general, the children demonstrated severe language, cognitive and motor delays, as measured by Bayley-III, and severe neurological symptoms, as recorded by the HINE. However, the HINE and Bayley-III raw scores effectively captured heterogeneity in these symptoms. Greater head circumference at follow-up was associated with higher cognitive (? = 1.27; 95% CI = 0.01-2.53) and motor raw scores (? = 2.03; 95% CI = 0.25-3.81). Better HINE scores were also correlated with higher Bayley-III cognitive and motor raw scores, even after controlling for other factors. The study was the first to associate HINE — a short and easy neurological examination tool — with cognitive and motor development in children with CZS. The authors conclude that HINE may be a useful tool to characterize long-term outcomes, and capture the clinical heterogeneity, of children with CZS-associated microcephaly.
The authors add: “Children with CZS-associated microcephaly demonstrate severe neurodevelopmental impairments. However, they have heterogeneous development patterns and it is necessary to understand the differences between these children to provide a better health intervention.”
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Materials provided by PLOS. Note: Content may be edited for style and length.

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Likely cause of Alzheimer’s disease identified

Ground-breaking new Curtin University-led research has discovered a likely cause of Alzheimer’s disease, in a significant finding that offers potential new prevention and treatment opportunities for Australia’s second-leading cause of death.
The study, published in the PLOS Biology journal and tested on mouse models, identified that a probable cause of Alzheimer’s disease was the leakage from blood into the brain of fat-carrying particles transporting toxic proteins.
Lead investigator Curtin Health Innovation Research Institute (CHIRI) Director Professor John Mamo said his collaborative group of Australian scientists had identified the probable ‘blood-to-brain pathway’ that can lead to Alzheimer’s disease, the most prevalent form of dementia globally.
“While we previously knew that the hallmark feature of people living with Alzheimer’s disease was the progressive accumulation of toxic protein deposits within the brain called beta-amyloid, researchers did not know where the amyloid originated from, or why it deposited in the brain,” Professor Mamo said.
“Our research shows that these toxic protein deposits that form in the brains of people living with Alzheimer’s disease most likely leak into the brain from fat carrying particles in blood, called lipoproteins.
“This ‘blood-to-brain pathway’ is significant because if we can manage the levels in blood of lipoprotein-amyloid and prevent their leakage into the brain, this opens up potential new treatments to prevent Alzheimer’s disease and slow memory loss.”
Building on previous award-winning research that showed beta-amyloid is made outside the brain with lipoproteins, Professor Mamo’s team tested the ground-breaking ‘blood-to-brain pathway’ by genetically engineering mouse models to produce human amyloid-only liver that make lipoproteins.

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COVID-19 virus rapidly evolves to higher infectivity during in vitro growth, which may be a step toward lower virulence

Viruses accumulate mutations as they replicate in infected cells. Repeated replication can lead to viral strains that show attenuated virulence. Such strains may act as vaccines if the attenuated virus can produce immunity without serious disease.
This approach is not new. Albert Sabin developed an attenuated poliovirus vaccine in the mid-20th century that helped eradicate naturally occurring polio in the Western Hemisphere. Attenuated viral vaccines for rubella, measles, yellow fever and other diseases are widely used.
Can a similar vaccine be developed for COVID-19?
Researchers at the University of Alabama at Birmingham have published a foundational study for that possibility in the Journal of Virology. They asked a simple question: Which mutations predominate when the SARS-CoV-2 virus that causes COVID-19 is grown in successive generations — called passages by virologists — in tissue culture?
The UAB researchers found that SARS-CoV-2 isolates rapidly adapted as they grew in repeated passages in Vero E6 cells, a strain of kidney cells that is commonly used for virus propagation. The evolved viruses gained higher infectivity, demonstrated more rapid infection spread and made dramatically larger plaques on Vero cells. A plaque is a visible fragment of the cell layer where cells are destroyed by viral multiplication and release.
For one of the SARS-CoV-2 strains tested by UAB researchers — a strain from Washington state that was the first COVID-19 virus detected in the United States at the start of 2020 — the average number of infectious virus particles released from the cells was 100-fold less than the number of infectious particles released after four passages.

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I’m Vaccinated. When Should I Wear a Mask?

I’m Vaccinated. When Should I Wear a Mask?Noah PisnerReporting on the coronavirusSo, why are Covid vaccines effective at preventing you from getting severely sick, but not as good at stopping transmission of the virus?The vaccines are injected deep into your arm where they prompt your immune system to produce T cells and powerful antibodies known as IgG.These antibodies and immune cells circulate through your body, recognizing infected cells. This can offer enough protection to keep you from becoming severely ill.

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New study challenges understanding of pandemic preparedness and resilience in Africa

Countries in Africa assessed as being least vulnerable to an epidemic were the worst affected by Covid-19, new research suggests.
Nations with more urban populations and strong international travel links were worst affected by the pandemic, the study shows.
Mortality rates and levels of restrictions — such as lockdowns and travel bans — were found to be lowest in countries previously thought to be at greatest risk from Covid-19.
A team of researchers from the NIHR Global Health Research Unit Tackling Infections to Benefit Africa (TIBA) from the University of Edinburgh worked with the World Health Organization (WHO) African Region to identify factors affecting mortality rates during Africa’s first two Covid-19 waves and the timing of the first reported cases.
Professor Mark Woolhouse, TIBA Director, who co-led the study, said: “Our study shows very clearly that multiple factors influence the extent to which African countries are affected by Covid-19. These findings challenge our understanding of vulnerability to pandemics.
“Our results show that we should not equate high levels of preparedness and resilience with low vulnerability.

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Older age, chronic co-morbidities associated with more severe COVID disease in children

Over the course of the pandemic, researchers nationwide noticed differences in COVID-19 disease between children and adults.
While risk factors for hospitalization and poor outcomes are well documented in adults, less is known about the clinical factors associated with COVID disease severity in children.
In an effort to aid mitigation strategies for children who are at high risk of developing severe COVID disease, a group of physicians at Monroe Carell Jr. Children’s Hospital at Vanderbilt studied data from 45 children’s hospitals around the country — 20,000 patients were included.
“This is one of the largest multicenter studies of children with COVID-19 in the United States,” said James Antoon, MD, PhD, FAAP, assistant professor of Pediatrics at Children’s Hospital and lead author of the study.
“And given the recent, concerning increases in COVID cases nationwide and the fact that the vast majority of children remain unvaccinated and susceptible, these findings should be taken into account when considering preventive strategies in schools and planning vaccinations when available for children less than 12 years of age,” he said.
The study, “Factors Associated with COVID-19 Disease Severity in U.S. Children,” published in the Journal of Hospital Medicine, determined the factors associated with severe disease and poor health outcomes among children presenting to the hospital with COVID. These included older age and chronic co-morbidities such as obesity, diabetes and neurologic conditions, among others.
“These factors help identify vulnerable children who are most likely to require hospitalization or develop severe COVID-19 disease,” said Antoon. “Our findings also highlight children who should be prioritized for COVID-19 vaccines when approved by the FDA.”
The retrospective cohort study noted that approximately 1 out of every 4 children admitted to the hospital with COVID developed severe disease and required ICU care during April and September, 2020.
“Across the country there is a raging debate on how best to protect children and schools from COVID-19,” said Antoon. “Some children are at increased risk for more severe disease and many of them are not yet eligible for vaccination against COVID.
“With schools opening and some already in session, these children need to be protected by vaccinating as many people as possible while also using practical strategies to limit spread, such as masking, distancing and ventilation.”
Study investigators hope that the findings will buoy mitigation efforts that proved most beneficial for children and adolescents during the pandemic, including remote learning, social distancing, hand-washing and mask-wearing both for students and teachers.
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Materials provided by Vanderbilt University Medical Center. Original written by Jessica Pasley. Note: Content may be edited for style and length.

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Making musical performances safer in the era of COVID-19

One of the many aspects of “normal” life that SARS-CoV-2 took away was the enjoyment of live musical performances. With the easing of lockdowns and restrictions in many parts of the world, performers can entertain audiences once again, but concerns about spreading the virus remain. Now, researchers reporting in ACS Environmental Au have studied aerosol production from playing wind instruments, singing and acting, allowing them to develop recommendations to minimize COVID transmission.
Early in the pandemic, COVID-19 outbreaks from choir performances indicated that singing carries a potential infection risk, but less is known about the risks of airborne infection from wind instruments. To help keep performers, audiences and music students safe, Tehya Stockman, Shelly Miller and colleagues wanted to examine aerosol production and flow from various musical activities, as well as test different mitigation strategies.
The researchers examined the extent and velocity of air jets, or plumes, coming from singers’ and actors’ mouths and from wind instruments, such as the flute, clarinet, trumpet and saxophone. They also measured airborne respiratory particles, or aerosols, and carbon dioxide levels emanating from the performers. They found that aerosol concentrations coming from the bell of a clarinet were comparable to singing. Placing a surgical mask over a singer’s face or over the clarinet bell substantially reduced plume velocities and lengths and decreased aerosol concentrations in front of the masks. The team then used these measurements to model viral transmission in indoor and outdoor environments, finding that the lowest risk of airborne COVID-19 infection occurred at less than 30 minutes of exposure indoors and less than 60 minutes outdoors. These findings could help musical rehearsals and performances resume in a safer manner for musicians and audiences, the researchers say.
The authors acknowledge funding from an international coalition of more than 95 musical organizations.
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Materials provided by American Chemical Society. Note: Content may be edited for style and length.

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