Monday, November 25, 2024

 

New insights reveal how house dust mites trigger allergic asthma by activating the immune system




University of Pittsburgh
Mouse lymph node with hotspots of IL2 activity circled 

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Mouse lymph node with hotspots of IL2 activity circled

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Credit: Kun He




New research from the University of Pittsburgh uncovers how inhaled house dust mites, a common trigger of allergic asthma, activate the immune system and drive this disease in mice.

The findings, published recently in Nature Immunology, offer important insights into how seemingly harmless substances such as dust mites, pet dander and pollen can overcome the immune system to trigger allergic reactions and could eventually pave the way for identifying new therapeutics to treat and manage allergic asthma.

“We often think of the immune system as an army that fights the bad guys,” said senior author Amanda C. Poholek, Ph.D., director of the Health Sciences Sequencing Core and assistant professor in the Department of Immunology at Pitt’s School of Medicine. “And while that’s true, most of the time your immune system is not encountering pathogens but dealing with dust and pollen that you breathe in, plants and animals that you eat, and things that you touch in the environment. A big question that motivates my research is: How does our immune system know to respond to pathogens and not to self and the environment?”

When the immune system does this job correctly, it’s known as immune tolerance. But when tolerance breaks down, typically harmless environmental allergens can activate T Helper 2 (Th2) cells, which are a type of immune cell that drives inflammation in allergic asthma and other allergic diseases.

Allergic asthma is the most common form of asthma, characterized by symptoms such as coughing, chest tightness, shortness of breath and wheezing. This debilitating condition is on the rise worldwide and places a substantial burden on the health care system, according to Poholek.

To learn more about how allergens activate Th2 cells and cause allergic asthma, Poholek and her team used a mouse model of the disease triggered by inhalation of house dust mites. This model is a more accurate representation of how humans encounter allergens compared to studies that used under-the-skin or systemic injections of allergen.

Using new tools that allowed them to track Th2 cells and see exactly when they get activated and where they went, the researchers found that in response to inhaled house dust mite, a specific molecular pathway involving a protein called BLIMP1 was needed to generate Th2 cells in the lymph node. These cells then move to the lung and drive disease. In contrast, when house dust mite is injected, that molecular pathway is not needed.

They also found that two signaling molecules, or cytokines, called IL2 and IL10 were required for expression of BLIMP1.

“IL10 is normally thought of as an anti-inflammatory cytokine, which dampens immune responses, so we were really surprised to find that it was actually promoting inflammation,” said Poholek. “This finding opens that door to therapeutic options targeting IL10, which hadn’t previously been considered, particularly for newly diagnosed patients.”

According to Poholek, most patients with allergic asthma receive steroids, which treat the symptoms but not the root of the disease. There is a huge need for new treatments that allow early intervention before allergic asthma causes long-term damage to the airways.

When the researchers mapped the location of Th2 activation in the lymph node, they were also surprised to find hotspots of IL2 activity.

“IL2 is a very prominent cytokine, so we expected that it would be dispersed throughout the lymph node,” said Poholek. “Instead, we discovered that IL2 was localized to certain regions. Now, we have a lot more work to figure out how these regions form and whether disrupting these regions could disrupt the formation of Th2 cells, halting allergic asthma.”

In collaboration with colleagues in the Pitt Division of Pulmonology, Allergy, Critical Care and Sleep Medicine, Poholek is also planning to look at lung tissue samples to investigate whether IL2 and IL10 could also be important drivers of Th2 cells in patients with allergic asthma and explore potential avenues for developing new therapeutic options.

Other authors are listed in the Nature Immunology paper.

This work was supported by the National Institutes of Health (DP2AI164325, AI153104 and AI156093), the American Lung Association Innovation Award, the Research Advisory Committee at UPMC Children’s Hospital of Pittsburgh and the Clinical and Translational Science Institute Pilot Award.

 

 

Fewer than 1 in 5 know the 988 suicide lifeline





Annenberg Public Policy Center of the University of Pennsylvania
Public knowledge of the Suicide & Crisis Lifeline 

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US adults who know that 988 is the Suicide and Crisis Lifeline. From the Annenberg Public Policy Center's Annenberg Science and Public Health (ASAPH) knowledge surveys from January 2023-September 2024.

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Credit: Annenberg Public Policy Center





PHILADELPHIA – Annenberg Public Policy Center survey data show that public recall of the 988 Suicide & Crisis Lifeline number has grown slowly since the three-digit phone number was introduced in July 2022. Just 15% of U.S. adults are familiar with it, as of September 2024.

Survey respondents who accurately report awareness of the Suicide & Crisis Lifeline number increased significantly from August 2023 (11%) to September 2024 (15%). Those 15% of respondents reported both that they knew the number and, when asked in an open-ended format, said the number was 988. The number who inaccurately reported that the number was 911 (the nationwide emergency phone number) decreased to 1% in September 2024 from 4% in August 2023.

“The help that can be found at the 988 helpline can only save lives if those in need and their loved ones and friends know the number,” said Kathleen Hall Jamieson, director of the Annenberg Public Policy Center of the University of Pennsylvania. “When 988 is as readily recalled as 911, the nation will have cause to celebrate.”

Although the survey found a year-over-year increase, it did not detect an increase in accurate responses between October 2023 and September 2024, a period that included the launch of an eight-month 988 awareness ad campaign by the Substance Abuse and Mental Health Services Administration (SAMHSA) in June 2024. The SAMHSA media campaign targets especially vulnerable subsets of the population, which may be too small to impact the overall awareness estimates in our nationally representative, general population sample.

APPC’s Annenberg Science and Public Health knowledge survey

The survey data come from the 21st wave of a nationally representative panel of 1,744 U.S. adults conducted for the Annenberg Public Policy Center by SSRS, an independent market research company. Most have been empaneled since April 2021. To account for attrition, small replenishment samples have been added over time using a random probability sampling design. The most recent replenishment, in September 2024, added 360 respondents to the sample. This wave of the Annenberg Science and Public Health Knowledge (ASAPH) survey was fielded Sept. 13-22 and Sept. 26-30, 2024. The margin of sampling error (MOE) is ± 3.5 percentage points at the 95% confidence level. All figures are rounded to the nearest whole number and may not add to 100%. Combined subcategories may not add to totals in the topline and text due to rounding.

Download the topline and the methods report.

The policy center has been tracking the American public’s knowledge, beliefs, and behaviors regarding vaccination, Covid-19, flu, RSV, and other consequential health issues through this survey panel over the past two-and-a-half years. In addition to Jamieson and Gibson, APPC’s team on the survey includes research analyst Shawn Patterson Jr., Patrick E. Jamieson, director of the Annenberg Health and Risk Communication Institute, and Ken Winneg, managing director of survey research.

The Annenberg Public Policy Center was established in 1993 to educate the public and policy makers about communication’s role in advancing public understanding of political, science, and health issues at the local, state, and federal levels.

 

New nasal vaccine shows promise in curbing whooping cough spread



With whooping cough cases on the rise new nasal vaccine aims to stop transmission



Tulane University




As whooping cough cases rise in the U.S., a new nasal vaccine developed by Tulane University may hold the key to reducing the spread of the highly contagious respiratory disease.

Current pertussis vaccines are widely used and effective at preventing whooping cough, caused by the Bordetella pertussis bacteria.  However, the vaccines fail to clear bacteria from the upper respiratory tract, allowing even vaccinated individuals to spread the disease.

The new vaccine combines the traditional pertussis antigens with an innovative adjuvant called T-vant, which boosts the body’s immune response specifically in the respiratory tract. In a study published in npj Vaccines, mice immunized intranasally with the new T-vant vaccine showed no signs of the bacteria in the lungs and nasopharynx – the upper throat area behind the nose – three weeks after infection. The bacteria remained prevalent in upper respiratory tract of mice that received the traditional vaccine intramuscularly.

“By developing a vaccine that can not only protect individuals but also prevent transmission, we hope to improve on existing vaccines and limit the spread of whooping cough in communities,” said lead study author Lisa Morici, professor of microbiology and immunology at Tulane University School of Medicine.

The T-vant adjuvant is derived from bacterial outer membrane vesicles, tiny particles that naturally stimulate the immune system. The study found that the adjuvant encouraged a mucosal immune response, spurring the activation of immune cells in the respiratory tract critical for halting the bacteria’s ability to colonize.

The study also found no adverse effects on lung tissue following immunization, highlighting the vaccine’s safety.

The findings are significant and come at a time when whooping cough cases are surging. Recent data from the Centers for Disease Control and Prevention showed a five-fold increase in U.S. cases over last year. The disease affects roughly 24 million people a year worldwide and primarily impacts infants and those with weakened immune systems.

A vaccine that can successfully prevent infection and transmission of whooping cough in humans could lay the groundwork for eliminating the disease altogether, said James McLachlan, co-author of the study and associate professor of microbiology and immunology at Tulane School of Medicine.

“These findings underscore the need for enhanced vaccines that can do more than just protect the individual,” McLachlan said. “We need vaccines that can effectively stop the bacteria from spreading within communities, and this new approach offers an encouraging step in that direction.”

T-vant was developed through support from the NIH Adjuvant Development Program. More information on T-vant can be found at https://vac.niaid.nih.gov/view?id=61.

 

Anti-anxiety and hallucination-like effects of psychedelics mediated by distinct neural circuits



Mouse study suggests path to decouple benefits from hallucinogenic effects



University of California - Davis

Anti-Anxiety and Hallucination-Like Effects of Psychedelics Mediated by Distinct Neural Circuits 

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Working in a mouse model, UC Davis researchers are able to distnguish brain cells activated by a psychedelic drug. This image shows the prefrontal cortex of a mouse injected with scFLARE2 (purple) which drives the expression of a light-responsive channel in psychedelic-activated neurons (green or red). This allows researchers to visualize and artificially reactive these neurons at a later time point. 

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Credit: Christina Kim, UC Davis




New research suggests that it could be possible to separate treatment from hallucinations when developing new drugs based on psychedelics. The anti-anxiety andhallucination-inducing qualities of psychedelic drugs work through different neural circuits, according to research using a mouse model. The work is published Nov. 15 in Science

The research shows that decoupling the beneficial effects of psychedelics from their hallucinogenic effects isn’t just a matter of chemical compound design. It’s a matter of targeted neural circuitry.

“In the past, we did this using chemistry by making new compounds, but here we focused on identifying the circuits responsible for the effects, and it does seem that they are distinct,” said study co-author David E. Olson, director of the Institute for Psychedelics and Neurotherapeutics (IPN) and a professor of chemistry and of biochemistry and molecular medicine at the University of California, Davis. “This is an important mechanistic study that validates our earlier results.” 

Measuring anti-anxiety behaviors in mice

The researchers measured anxiety in mouse models with two tests: the elevated plus maze and the marble burying test. 

In the elevated plus maze, mice are placed in a cross-shaped maze raised a couple of feet off the ground. Two arms of the maze have high walls while the other two arms remain open and have no walls. Mice with high anxiety tend to stay in the closed arms with high walls, not willing to explore the open arms.

In the marble burying test, mice with high anxiety tend to continuously and compulsively bury marbles in their bedding. 

“It is well known that in mice, psychedelics induce reduced marble burying and promote exploration of the open arms of the plus maze,” said Christina Kim, the study’s corresponding author and an assistant professor of neurology, core member of the Center for Neuroscience and IPN affiliate. “But there is also an intoxicating or hallucinogenic-like effect, which can be measured through head twitches in mice.” 

In the study, the team dosed mouse models with the psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI). They found that six hours after the dose, the mice still exhibited reduced marble burying and increased open arm time in the elevated plus maze. However, the head twitches associated with hallucinations had disappeared. 

“We thought that if we could identify which neurons activated by DOI were responsible for reducing anxiety, then we might be able to reactivate them at a later time to mimic those anti-anxiety-like effects,” Kim said. 

To identify the specific neural circuits associated with anti-anxiety effects, the team used a molecular tagging tool called scFLARE2 to highlight the neurons activated by DOI in the medial prefrontal cortex — a brain region known to be involved in reducing anxious behavior in mice. 

The tagging allowed the team to isolate a psychedelic responsive network that extends beyond 5-HT2AR expressing neurons, the main receptor avenue through which psychedelics promote neuroplasticity. 

Using light to promote anti-anxiety effects

Equipped with a fluorescent map of the neurons activated by DOI, the team then used optogenetics, or light, to reactivate those neurons.

“When we performed the scFLARE2 tagging and reactivation of these specific prefrontal cortex cells, we could still drive a reduction in anxiety-like behaviors, measured as decreased marble burying and increased open arm exploration in the elevated plus maze,” Kim said. “We could do this just by targeting the DOI-activated cells and then reactivating them the next day.” 

The team also used single nucleus RNA sequencing to genetically profile the specific types of neurons in the DOI-activated network. Of the nine neuron group types identified, three exhibited high activation.

“While some of the cell types activated by DOI had strong 5-HT2AR expression, there were others that did not,” Kim said. “What is likely happening is that we are getting direct activation of cells that express 5-HT2AR, and then they go on to activate additional downstream cells that can trigger behavioral changes.” 

“It is important to realize that the cells that we are tagging and reactivating extend beyond just those that express the receptor for the drug,” she added.

The finding emphasizes how activating single touchpoints in the brain spirals out into the rest of the network. 

“While DOI is a potent psychedelic, it is not being explored as a potential therapeutic drug in the clinic. Thus the findings here are focused on dissecting the basic circuit mechanisms of this important class of drugs,” Kim said.

Elucidating exactly how psychedelics affect the brain is a major goal of the IPN. 

“Understanding which neural circuits psychedelics activate to elicit their effects is the kind of basic science needed to ultimately develop targeted therapeutics with better safety profiles,” Olson said. 

Co-authors Jessie Muir, a postdoctoral researcher at the Center for Neuroscience, and Sophia Lin, a junior specialist at the Center for Neuroscience, spearheaded the DOI study. Additional authors on the study include I.K. Aarrestad, H.R. Daniels, J. Ma and L. Tian.

Funding for the research was provided by the Burroughs Wellcome Fund Career Award at the Scientific Interface, the Brain & Behavior Research Foundation Young Investigator Award, the Searle Scholars Program, The Kavli Foundation, the UC Davis Behavioral Health Center for Excellence Pilot Award, the Canadian Institutes of Health Research postdoctoral training award, the National Institutes of Health, the Boone Family Foundation and the Camille Dreyfus Teacher-Scholar Award. 

 

For low-risk pregnancies, planned home births just as safe as birth center births, study shows



Oregon State University
Home birth 

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Kāla Noel captured this image of the Wagar family welcoming their baby at a planned home birth. Photo shared by Melissa Cheyney, professor in the OSU College of Liberal Arts and a licensed midwife.

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Credit: Kāla Noel captured this image of the Wagar family welcoming their baby at a planned home birth. Photo shared by Melissa Cheyney, professor in the OSU College of Liberal Arts and a licensed midwife.



CORVALLIS, Ore. – In low-risk pregnancies, mothers and children are just as safe with a planned home birth as they are with a planned birth center birth, a national study led by Oregon State University researchers has shown.

The findings, published in Medical Care, contradict doctors’ long-held concerns about home birth, including a recent opinion by the American College of Gynecologists and Obstetricians that describes hospitals and accredited birth centers as the safest places to have a baby. A birth center is a health care facility designed to provide a more natural and home-like environment than a hospital.

OSU scientists analyzed two national registries for community births – planned birth either at home or in a birth center for low-risk pregnancies – in the largest study to examine how the settings compared to each other in terms of health outcomes.

A low-risk pregnancy is defined as a single baby being carried to full term (at least 37 weeks) and positioned with its head down, with no major maternal complications such as diabetes or pre-eclampsia. At least 70% of pregnancies are low risk, said Marit Bovbjerg, an associate professor in the Oregon State College of Health.

Combined, the two registries documented more than 110,000 births from 2012 to 2019, representing all 50 U.S. states, and the data showed no safety difference between home birth and birth center birth.

“Historically, physicians in the U.S. have objected to planned home births but not planned birth center births, even though from both settings you would need to transfer the birthing person to a hospital for any major complications,” Bovbjerg said. “Until now, we’ve had no evidence about home versus birth center outcomes. Our study is the first to provide evidence that these two birth settings are equally safe.”

Bovbjerg and Melissa Cheyney, a professor in the OSU College of Liberal Arts and a licensed midwife, did not directly compare the safety of community settings to hospitals but they note that the bulk of evidence globally, including a U.S. National Academies of Science, Engineering and Medicine report published in 2020, supports the idea that planned community birth is a safe alternative to hospital birth.

“That means that within the U.S., we already had evidence that birth centers were comparable to hospitals for low-risk births,” said Bovbjerg, who with Cheyney co-directs Oregon State’s Uplift Lab. “Our study compared home to birth center and suggests that both community settings are a reasonable choice for low-risk birthing people.”

The scientists note that the rate of home birth in the United States has been increasing over the last two decades, and that 2% of births in the U.S. happen in one of the two types of community settings, which have similar attendants and interventions available but different practice standards, regulatory guidelines and levels of health systems integration.

They added that planned home birth resulted in a lower rate of transfer to hospital than planned birth center birth for reasons that could relate to concern over negative hospital experiences.

“They might fear a loss of continuity of care provider, as well as possible mistreatment and judgment upon arrival at the hospital,” Cheyney said, citing a national care-experience study in which many participants reported mistreatment, including being ignored, scolded, shouted at or subject to an invasive procedure without consent.

“That was especially true for Black and Indigenous people who transferred to a hospital from a planned home birth,” she said. “If previous hostile transfer experiences contribute to a reluctance to transfer, we obviously need to work together to improve the transfer experience. Transfer from community settings is often necessary, and anything that discourages a necessary transfer likely causes harm.”

The collaboration also included researchers from the American Association of Birth Centers, Georgia State University, Frontier Nursing University, the University of Denver and the University of British Columbia.

 

Edible bird's nest-infused beverage: A new weapon in the fight against hypertension




Zhejiang University





A recent study highlights the health benefits of a cocoa-flavored, soy-based powder drink mix enriched with hydrolysates from edible bird's nests. This innovative functional beverage shows promise in managing hypertension and inflammation, along with improving glycemic control and prolonging satiety. The study focuses on the drink's angiotensin-converting enzyme (ACE) inhibition and red blood cell membrane stabilization effects, suggesting a fresh approach to dietary management of chronic health issues.

As consumer demand for functional foods rises, powdered drink mixes (PDMs) have gained popularity due to their convenience and health benefits. This shift reflects an increasing preference for plant-based or specialty beverages addressing dietary concerns like lactose intolerance and calorie control. Low-glycemic foods are especially valued for managing blood glucose levels and enhancing satiety, making them beneficial for diabetes care and weight management. Given these demands, there is a growing need for research to create new health-promoting PDMs that meet evolving dietary needs.

This study (DOI: 10.1093/fqsafe/fyae044) was conducted by a research team from Universiti Kebangsaan Malaysia and was published in the Journal of Food Quality and Safety on October 3, 2024. Researchers investigated the effects of edible bird’s nest hydrolysates (EBNH) in a cocoa-flavored soy PDM, designed to maximize health benefits. Key results showed enhanced angiotensin-converting enzyme (ACE) inhibitory activity and red blood cell membrane stabilization, both of which are linked to antihypertensive and anti-inflammatory effects. The drink’s formulation also features a low glycemic index and prolonged satiety, making it particularly effective for managing blood sugar levels and appetite.

The research team developed a novel soy-based PDM fortified with EBNH, known for its bioactive properties. Tests showed that the drink effectively inhibits ACE activity, suggesting antihypertensive potential by blocking compounds that raise blood pressure. In human trials, the drink demonstrated a low glycemic index, helping to keep postprandial blood glucose levels stable. Participants reported feeling full for up to 2.5 hours after consuming the drink, attributed to its high protein and fiber content. With 3% EBNH, the formulation delivers notable antioxidant effects that help stabilize red blood cells and reduce inflammation, key for managing hypertension and diabetes. Additionally, this low-calorie, high-fiber PDM offers a valuable dietary choice for those with specific health needs or dietary restrictions, underscoring EBNH’s potential in developing functional foods for chronic health management.

Dr. Zalifah Mohd Kasim, lead researcher and senior lecturer at Universiti Kebangsaan Malaysia, commented on the impact of the findings: “The incorporation of EBNH into powdered drink mixes offers a novel way to enhance everyday nutrition with bioactive benefits. This fortified drink mix could serve as an effective dietary option for individuals managing hypertension and diabetes, or anyone looking for sustained energy and satiety. Our findings support the increasing interest in functional foods that address hunger while promoting better health outcomes.”

The enriched cocoa-flavored soy drink holds promise as a dietary supplement for individuals looking for functional foods to support blood pressure, blood sugar, and appetite control. Its high protein, low-calorie, and low glycemic profile aligns well with dietary recommendations for diabetes care and weight management. As consumer demand for therapeutic, plant-based foods grows, this product provides a convenient, health-focused option.

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References

DOI

10.1093/fqsafe/fyae044

Original Source URL

https://doi.org/10.1093/fqsafe/fyae044

Funding information

The authors would like to thank Universiti Kebangsaan Malaysia (UKM) for providing financial support through the research project grants GUP-2018-059.

About Food Quality and Safety

Food Quality and Safety (FQS) is an open access, international, peer-reviewed journal providing a platform to highlight emerging and innovative science and technology in the agro-food field, publishing up-to-date research in the areas of food quality, food safety, food nutrition and human health. It is covered by SCI-E and the 2023 Impact Factor (IF)=3.0, 5-yr IF=4.7.