Researchers from University College London (UCL) looked at what schools are expected to teach 14–18-year-olds across the UK, using curriculum requirements and specifications set by exam boards. Findings, published today in the peer-reviewed journal Human Fertility, demonstrate significant gaps and variations in what pupils are taught about sexual and reproductive health.

The study’s senior author is award-winning Professor Joyce Harper, Head of the Reproductive Science and Society Group at the UCL EGA Institute for Women’s Health, who has worked in the fields of fertility, genetics, reproductive health and women’s health for over 30 years.

She states the current curriculum is leaving children with a “lack of understanding of concepts that are needed for their reproductive health”.

“We have found significant variation and gaps in the current UK science and biology curricula for 14–18-year-olds as they relate to sexual and reproductive health: there is potential for better alignment of science, and relationships and sex education teaching,” she adds.

Professor Harper, and the rest of the research team at UCL, found most pupils are expected to learn about sexually transmitted infections; hormonal aspects of reproduction; contraception; the menstrual cycle; and assisted reproductive technology. However, important topics such as endometriosis, fertility, preconception health, pregnancy, miscarriage and menopause are missing from the curriculum and from science exams.

There are substantial differences between the nations of the UK, with Scotland having the most comprehensive coverage in its curriculum.

The findings matter because these issues are experienced by large numbers of adults, the researchers say – menopause is an almost universal transition for women, while endometriosis affects around 10 per cent and a quarter of known pregnancies end in miscarriage. HIV, other sexually transmitted infections and unwanted pregnancy cost health services large amounts of money.

“Better reproductive health education is crucial if young people are to understand their reproductive systems and to make informed decisions about their sexual lives and fertility, including whether they want to have children or not,” Professor Harper, who hosts the podcast ‘Why didn’t anyone tell me this?’ and is author of the book ‘Your Fertile Years’, adds.

“Government departments, teachers, parents and others should all play a role in deciding what to include in the school curriculum.

“Poor fertility education at school is a major reason for people being unable to have children when they want them.

“Improvements in education could also help address unrealistic media portrayals of fertility and the relatively low success of procedures such as IVF.”

The study looks at both relationships and sex education curricula and exam specifications for biology and science in relation to reproductive health. It included analysis of new RSE guidance for England which was introduced in 2020, and Scottish advice and guidance on relationships, sexual health and parenthood education. There is no comparable guidance for Northern Ireland or Wales.

The results reveal significant differences in the content of the sex and reproductive health education curricula across the UK, with gaps in the comprehensiveness with which relevant topics are taught. For instance, miscarriage and menopause are included in the curriculum in Scotland but not in England. There is little about LGBTQ+ relationships, and students are not usually asked to consider what they might do if they found themselves pregnant but did not want to have children. There is also a “worrying lack” of acknowledgement that sexual and reproductive health is an important aspect of an individual’s overall wellbeing.

Following the findings, the research team is preparing to work with five schools to see how they may use a teachers’ resource which they’ve created with the International Reproductive Health Education Collaboration, which Harper founded and chairs.

McMaster researchers Deborah Sloboda and Katherine Kennedy examined prenatal stool (meconium) samples collected from 20 babies during breech Cesarean delivery.

“The key takeaway from our study is we are not colonized before birth. Rather, our relationship with our gut bacteria emerges after birth and during infancy,” said Kennedy, first author of the study and a PhD student, whose findings are published in Nature Microbiology.

Recent studies have sparked controversy by claiming that we are colonized by gut bacteria before birth. But, Kennedy said, studies such as these have been criticized for the ways they control for contamination.

“By including only breech caesarean deliveries in healthy pregnant women we were able to avoid the transmission of bacteria that occurs naturally during a vaginal birth,” said Thorsten Braun, co-senior author and lead obstetric consultant and deputy director of the Department of ‘Experimental Obstetrics’ at Charité — Universitätsmedizin Berlin.

Kennedy said recent data suggest that a person’s relationship with their own gut bacteria is most important in early life, during critical stages of immunological and physiological development.

Sloboda, co-senior author, agrees.

“The fact that colonization of infants’ guts occurs during and after their births, means that not only is it vulnerable to early environmental influences, but could also offers a window of potential intervention,” said Sloboda, professor of biochemistry and biomedical sciences at McMaster and the Canada Research Chair in perinatal programming.

“While many of the exact mechanisms surrounding gut bacteria and their role in our early development is unclear, discovering when and how we are colonized is a key first step.”

Journal Reference:

1. Katherine M. Kennedy, Max J. Gerlach, Thomas Adam, Markus M. Heimesaat, Laura Rossi, Michael G. Surette, Deborah M. Sloboda, Thorsten Braun. Fetal meconium does not have a detectable microbiota before birth. Nature Microbiology, 2021; DOI: 10.1038/s41564-021-00904-0

University of Melbourne Dr Oanh Nguyen, Research Fellow at the Doherty Institute, said two significant findings of the research include understanding the biomarkers that drive recovery and identifying four specific cytokines that cause serious inflammation during influenza virus infection.

“Cytokines are key molecules needed for a robust immune response. However, too much of these cytokines can result in inflammation and in the case of influenza, much more serious infection,” Dr Nguyen said.

“We found four specific types of cytokines that would cause severe inflammation, and this provides clinicians the ability to predict whether a patient will become really sick with influenza.”

The team also consistently saw large populations of immune cells called T-follicular helper cells, working in parallel with antibody-secreting cells, in patients at around three days prior to their recovery.

“These findings are the first to report the importance of T-follicular helper cells during acute influenza virus infection, following previous discoveries from our work and others on the key role of these immune cells after influenza vaccination. Signs of these cells could be used as a biomarker for recovery from influenza,” Dr Nguyen said.

Professor Allen Cheng, Director of Infection Prevention and Healthcare Epidemiology at Alfred Health and Professor of Infectious Diseases Epidemiology at Monash University, said this had been a great collaboration between clinicians and immunologists, and a good example of ‘bedside to bench’ science.

“The COVID-19 pandemic, and before this, the swine flu pandemic, has highlighted the importance of improving our understanding of respiratory viral infections to improve the identification of patients at risk of severe outcomes and potentially future treatments,” Professor Cheng said.

University of Melbourne Professor Katherine Kedzierska, Laboratory Head at the Doherty Institute and world-leading influenza immunologist, said this research laid the groundwork for her team’s understanding of how the immune system responds to COVID-19.

“Because of our years of experience, experimental set up, knowledge and collaborations with Alfred Health for this and other influenza studies, we had the speed and agility to apply our work to immune studies of COVID-19,” Professor Kedzierska said.

“This influenza study was the blueprint for our COVID-19 research.”

Journal Reference:

1. Thi H. O. Nguyen, Marios Koutsakos, Carolien E. van de Sandt, Jeremy Chase Crawford, Liyen Loh, Sneha Sant, Ludivine Grzelak, Emma K. Allen, Tim Brahm, E. Bridie Clemens, Maria Auladell, Luca Hensen, Zhongfang Wang, Simone Nüssing, Xiaoxiao Jia, Patrick Günther, Adam K. Wheatley, Stephen J. Kent, Malet Aban, Yi-Mo Deng, Karen L. Laurie, Aeron C. Hurt, Stephanie Gras, Jamie Rossjohn, Jane Crowe, Jianqing Xu, David Jackson, Lorena E. Brown, Nicole La Gruta, Weisan Chen, Peter C. Doherty, Stephen J. Turner, Tom C. Kotsimbos, Paul G. Thomas, Allen C. Cheng, Katherine Kedzierska. Immune cellular networks underlying recovery from influenza virus infection in acute hospitalized patients. Nature Communications, 2021; 12 (1) DOI: 1038/s41467-021-23018-x

New research, published today in the journal Proceedings of the Royal Society B, reveals that reduced food intake in roundworms (Caenorhabditis elegans) has a detrimental effect on three generations of offspring — particularly when those descendants have access to unlimited food.

Lead researcher Dr Edward Ivimey-Cook, from UEA’s School of Biological Sciences, said: “We know that reduced food intake increases the lifespan in many animals and can potentially improve health in humans. However, little is known about the long-term effects of reduced food intake, including time-limited fasting, on distant descendants.

“We wanted to find out more about the potential long-term impact of fasting diets.”

The team investigated the effect of time-limited fasting on lifespan and reproduction in roundworms and across three generations of their descendants.

They studied more than 2,500 worms split across four generations. The first generation of worms were placed in one of four environments, including being able to eat as much as they liked, and being on a fasting diet.

Four generations of offspring from these parents were then placed onto either full-feeding or fasting diets.

The team then assessed the effects of different scenarios on the reproduction and longevity of future generations. These included what happens when great grandparents fast, but future generations are able to eat as much as they like, and cumulative fasting for four generations.

Dr Ivimey-Cook said: “We looked at what happens in roundworms. Unlike us, they’re transparent, about 1mm long and live in the soil.

“They don’t have bones, a heart, or a circulatory system. But they’re a classic model organism for studying the ageing process in biology because they do share many genes and molecular pathways that control development with humans.

“They are also really useful because they have a short life cycle of only two weeks, so we can study their development and that of generations of their offspring in a short amount of time. Doing a similar study across humans could take a century or more!

“We found that fasting did indeed increase their lifespan and it also improved offspring performance in terms of reproduction, when offspring themselves were fasting.

“However, we were surprised to find that fasting reduced offspring performance when the offspring had access to unlimited food.

“And this detrimental effect was evident in grand-offspring and great-grand-offspring.

“This shows that fasting can be costly for descendants and this effect may last for generations.

“There has been a lot of interest in the potential benefits of fasting in promoting healthy ageing in humans.

“A lot of the molecular pathways involved in the fasting response are evolutionarily conserved, which means the same pathways exist across a multitude of species including humans.

“So our study strongly prompts us to consider multigenerational effects of fasting in different organisms, including humans.

“This is really important because it means we need to carefully consider the long-term effects of fasting when trying to pursue healthy lifestyles — because the detrimental impact may only manifest itself in distant generations.”

The research was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the European Research Council (ERC).

Journal Reference:

1. Edward R. Ivimey-Cook, Kris Sales, Hanne Carlsson, Simone Immler, Tracey Chapman, Alexei A. Maklakov. Transgenerational fitness effects of lifespan extension by dietary restriction in Caenorhabditis elegans. Proceedings of the Royal Society B, 2021 [abstract]

Scientists at the University of North Carolina (UNC) School of Medicine have mapped out a serotonin-driven anxiety circuit that may explain this side effect and lead to treatments to eliminate it.

“The hope is that we’ll be able to identify a drug that inhibits this circuit and that people could take for just the first few weeks of SSRI use to get over that hump,” said senior investigator Thomas L. Kash, PhD, the John Andrews Distinguished Professor of Alcohol Studies in the UNC School of Medicine’s department of pharmacology. “More generally, this finding gives us a deeper understanding of the brain networks that drive anxiety and fear behavior in mammals.”

The new study, published in Nature, counters the popular view of serotonin as a neurotransmitter that promotes only good feelings. SSRIs, which are taken by about one in 10 people in the United States and about one in four women in their 40s and 50s, are thought to improve mood by boosting serotonin activity in the brain. There are brain circuits through which serotonin does seem to improve mood, and some studies have linked depression to abnormally low levels of serotonin. But the short-lived promotion of anxiety in many patients on SSRIs — even suicidal thinking, particularly in younger people — has long hinted that serotonin can have negative effects on mood, depending on the precise brain circuit where it acts.

In the Nature study, for which co-authors were UNC postdoctoral researcher Catherine A. Marcinkiewcz, PhD, and UNC graduate student Christopher M. Mazzone, the researchers used an array of sophisticated methods, including advanced optogenetic and chemogenetic tools, to trace a serotonin-activated pathway in the brains of mice, a pathway that drives anxious behavior.

The team first demonstrated that a mild shock to the paws of mice — a standard method for evoking fear and anxiety behaviors — activates serotonin-producing neurons in the dorsal raphe nucleus (DRN), a brainstem region known to be involved in mood and depression. These DRN serotonin neurons project to a brain region that is called the bed nucleus of the stria terminalis (BNST) and has been shown in previous studies to have a role in serotonin’s negative mood effects in rodents. Artificially increasing the activity of the DRN-to-BNST neurons enhanced anxiety-like behaviors in the mice.

UNC scientists found that the serotonin output from the DRN neurons activates their target neurons in the BNST through a specific subset of serotonin receptors, known as 2C receptors. These serotonin-activated BNST neurons then tamp down the activity of another family of BNST neurons, which, in turn, project to the ventral tegmental area (VTA) and lateral hypothalamus (LH) — key nodes in the brain’s reward, motivation and alertness networks.

The pathways from BNST to VTA and LH have been reported in previous studies to improve mood and relieve anxiety. Researchers confirmed that artificially driving the activity of these pathways has the effect of reducing foot-shock-induced fear and anxiety behaviors in the mice. By contrast, the silencing of these pathways by serotonin-activated BNST neurons effectively allows the anxiety level to rise.

Examining the impact of SSRIs, the scientists exposed 2C-receptor BNST neurons to fluoxetine (Prozac), which like other SSRIs gives a boost to serotonin levels wherever the neurotransmitter is at work. This turned out to increase the 2C-receptor neurons’ inhibitory effect on the neighboring VTA- and LH-projecting neurons, worsening fear and anxiety behavior in mice.

How can this effect be blocked? Kash and his team observed that the anxiety-mediating BNST neurons expressed the stress-signaling molecule corticotropin releasing factor (CRF). When they added a compound to block CRF activity, they witnessed that fearful behaviors — which had been triggered by fluoxetine — were greatly reduced.

One of the next steps is to confirm that this serotonin-sensitive DRN-to-BNST anxiety circuit exists in humans as well. “It’s logical that it would,” Kash said, “since we know SSRIs can induce anxiety in people, and the pathways in these brain regions tend to be very similar in mice and humans.”

Another next step will be to test drugs — ideally FDA-approved for various conditions — for their ability to alter this anxiety circuit and thereby block SSRIs’ anxiety-inducing effect. In principle, a CRF-blocker might work. For years, pharmaceutical companies have been trying to develop CRF blockers to treat depression, anxiety and addiction. In practice, Kash said, CRF blockers haven’t yet had success in clinical trials, so an FDA-approved one is probably still years away at least.

“Other researchers are working to develop better CRF-inhibiting compounds, so that’s one potential direction to take, but there are others,” Kash said. “We’re now looking at the various proteins expressed by these BNST neurons, and we’re hoping to identify a receptor that is already targeted by established drugs. One of them might be useful for people as they start taking SSRIs.”

Journal Reference:

1. Catherine A. Marcinkiewcz, Christopher M. Mazzone, Giuseppe D’Agostino, Lindsay R. Halladay, J. Andrew Hardaway, Jeffrey F. DiBerto, Montserrat Navarro, Nathan Burnham, Claudia Cristiano, Cayce E. Dorrier, Gregory J. Tipton, Charu Ramakrishnan, Tamas Kozicz, Karl Deisseroth, Todd E. Thiele, Zoe A. McElligott, Andrew Holmes, Lora K. Heisler, Thomas L. Kash. Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala. Nature, 2016; DOI: 10.1038/nature19318

Recurring seasonal flu epidemics and potential pandemics are among the most severe threats to public health. Current seasonal influenza vaccines induce strain-specific immunity and are less effective against mismatched strains. Broadly protective influenza vaccines are urgently needed.

Intranasal vaccines are a promising strategy for combatting infectious respiratory diseases, such as influenza. They are more effective than vaccines injected into a muscle because they can induce mucosal immune responses in respiratory tracts, preventing infection at the portal of virus entry. They can also stimulate systemic immune responses throughout the body.

Scientists can overcome vaccine safety concerns and the long production phase of virus-based influenza vaccines by constructing intranasal vaccines with recombinant proteins or peptides. However, these vaccines are poor at producing immune responses, so it’s necessary to have potent mucosal adjuvants, substances that enhance the body’s immune response to antigens (the molecular structures on pathogens). The absence of appropriate mucosal adjuvants currently hinders the development of such a vaccine.

In this study, the researchers developed an intranasal influenza vaccine using recombinant hemagglutinin (HA), a protein found on the surface of influenza viruses, as the antigen component of the vaccine. HA is integral to the ability of influenza virus to cause infection.

They also created a two-dimensional nanomaterial (polyethyleneimine-functionalized graphene oxide nanoparticles) and found that it displayed potent adjuvant (immunoenhancing) effects on influenza vaccines delivered intranasally. The findings are published in the journal Proceedings of the National Academy of Sciences.

“Conventional flu vaccines predominantly induce antibody responses,” said Dr. Baozhong Wang, senior author of the study, principal investigator of the National Institutes of Health grant supporting the study and a professor in the Institute for Biomedical Sciences. “However, recent research demonstrates that lung resident memory T cell responses are indispensable for optimal cross-protection against pulmonary influenza infection. The development of lung resident T cell responses requires vaccination by a respiratory route or influenza virus infection. Our research opens a new path for the development of needle-free and logistically simplified intranasal flu vaccines for cross-protection.”

“In our study, we reported for the first time that two-dimensional graphene oxide nanomaterials had a potent adjuvant effect in boosting the immune responses of intranasal hemagglutinin (HA) vaccines,” said Dr. Chunhong Dong, lead author of the study and a postdoctoral research Fellow in Dr. Baozhong Wang’s lab in the Institute for Biomedical Sciences.

“This study gives new insights into developing high performance intranasal vaccine systems with two-dimensional sheet-like nanoparticles,” Dong said. “The graphene oxide nanoparticles have extraordinary attributes for drug delivery or vaccine development, such as the ultra-large surface area for high-density antigen loading, and the vaccine showed superior immunoenhancing properties in vitro and in vivo. The nanoplatform could be easily adapted for constructing mucosal vaccines for different respiratory pathogens.”

The study, conducted in mice and cell culture, found the nanoparticles significantly enhanced immune responses at mucosal surfaces and throughout the body in mice. The robust immune responses conferred immune protection against influenza virus challenges by homologous (same) virus strains and heterologous (different) virus strains.

The results are also promising because needle-free, intranasal influenza vaccines possess superior logistical advantages over traditional injectable vaccines, such as easy administration with high acceptance for recipients and the avoidance of biohazardous waste.

Co-authors of the study include Dr. Chunhong Dong, Ye Wang, Gilbert Gonzalez, Yao Ma, Yufeng Song, Dr. Sang-Moo Kang and Dr. Baozhong Wang of the Institute for Biomedical Sciences at Georgia State and Shelly Wang and Dr. Richard W. Compans of Emory University School of Medicine.

The study was funded by the National Institutes of Health’s National Institute of Allergy and Infectious Diseases.

Journal Reference:

1. Chunhong Dong, Ye Wang, Gilbert X. Gonzalez, Yao Ma, Yufeng Song, Shelly Wang, Sang-Moo Kang, Richard W. Compans and Bao-Zhong Wang. Intranasal vaccination with influenza HA/GO-PEI nanoparticles provides immune protection against homo- and heterologous strains. PNAS, 2021 DOI: 10.1073/pnas.2024998118

Up to 20% of the world’s population suffers from the irritable bowel syndrome (IBS), which causes stomach pain or severe discomfort after eating. This affects their quality of life. Gluten-free and other diets can provide some relief, but why this works is a mystery, since the patients are not allergic to the foods in question, nor do they have known conditions such as coeliac disease.

“Very often these patients are not taken seriously by physicians, and the lack of an allergic response is used as an argument that this is all in the mind, and that they don’t have a problem with their gut physiology,” says Professor Guy Boeckxstaens, a gastroenterologist at KU Leuven and lead author of the new research. “With these new insights, we provide further evidence that we are dealing with a real disease.”

Histamine

His team’s laboratory and clinical studies reveal a mechanism that connects certain foods with activation of the cells that release histamine (called mast cells), and subsequent pain and discomfort. Earlier work by Professor Boeckxstaens and his colleagues showed that blocking histamine, an important component of the immune system, improves the condition of people with IBS.

In a healthy intestine, the immune system does not react to foods, so the first step was to find out what might cause this tolerance to break down. Since people with IBS often report that their symptoms began after a gastrointestinal infection, such as food poisoning, the researchers started with the idea that an infection while a particular food is present in the gut might sensitise the immune system to that food.

They infected mice with a stomach bug, and at the same time fed them ovalbumin, a protein found in egg white that is commonly used in experiments as a model food antigen. An antigen is any molecule that provokes an immune response. Once the infection cleared, the mice were given ovalbumin again, to see if their immune systems had become sensitised to it. The results were affirmative: the ovalbumin on its own provoked mast cell activation, histamine release, and digestive intolerance with increased abdominal pain. This was not the case in mice that had not been infected with the bug and received ovalbumin.

A spectrum of food-related immune diseases

The researchers were then able to unpick the series of events in the immune response that connected the ingestion of ovalbumin to activation of the mast cells. Significantly, this immune response only occurred in the part of the intestine infected by the disruptive bacteria. It did not produce more general symptoms of a food allergy.

Professor Boeckxstaens speculates that this points to a spectrum of food-related immune diseases. “At one end of the spectrum, the immune response to a food antigen is very local, as in IBS. At the other end of the spectrum is food allergy, comprising a generalised condition of severe mast cell activation, with an impact on breathing, blood pressure, and so on.”

The researchers then went on to see if people with IBS reacted in the same way. When food antigens associated with IBS (gluten, wheat, soy and cow milk) were injected into the intestine wall of 12 IBS patients, they produced localised immune reactions similar to that seen in the mice. No reaction was seen in healthy volunteers.

The relatively small number of people involved means this finding needs further confirmation, but it appears significant when considered alongside the earlier clinical trial showing improvement during treatment of IBS patients with anti-histaminics. “This is further proof that the mechanism we have unravelled has clinical relevance,” Professor Boeckxstaens says.

A larger clinical trial of the antihistamine treatment is currently under way. “But knowing the mechanism that leads to mast cell activation is crucial, and will lead to novel therapies for these patients,” he goes on. “Mast cells release many more compounds and mediators than just histamine, so if you can block the activation of these cells, I believe you will have a much more efficient therapy.”

Reference

KU Leuven. “Scientists reveal mechanism that causes irritable bowel syndrome.” ScienceDaily. ScienceDaily, 17 January 2021. <www.sciencedaily.com/releases/2021/01/210117132238.htm>.

“These results offer hope for patients with fragile X syndrome and their families,” said Elizabeth Berry-Kravis, MD, PhD, a paediatric neurologist at Rush University Medical Centre and principal investigator of the study. “The majority of clinical outcome measures were in favour of the drug. These measures included performance-based assessments, biomarkers, and parent and physician-rated scales, which in combination, suggest a meaningful impact on the global FXS disease process.”

The study was a phase two clinical trial to assess the safety and efficacy of a drug known as BPN14770 in 30 men with between the ages of 18 and 41 years who have fragile X syndrome. BPN1477 inhibits the activity of an enzyme known as phosphodiesterase-4D (PDE4D), which controls the availability in the brain of cyclic adenosine monophosphate (cAMP), a molecule that is critically involved in memory formation. By inhibiting PDE4D, the drug increases the levels of cAMP in the brain. “It’s exciting that we have a drug that potentially addresses a core biochemical deficit in FXS, a deficiency of cAMP, that has been documented in patients, and which I discovered during my paediatric neurology fellowship 30 years ago,” Berry-Kravis said.

Participants in the study received daily oral doses of BPN14770 twice a day or a placebo for 12 weeks. Parents, caregivers and physician raters were kept unaware of whether the participants received the treatment or the placebo.

The study evaluated the participants using a version of the National Institutes of Health (NIH) Toolbox Cognitive Battery (a cognitive measure) that, in work performed in collaboration with Dr. David Hessl at the UC Davis MIND Institute, was modified to be effective in assessing people with intellectual disabilities. In addition, the study included scales on which parents’ rated improvements from the drug.

“This is the first time that the NIH Toolbox has been able to be used to demonstrate a cognitive change in a trial in people with intellectual disabilities,” Berry-Kravis said. “In just three months, we saw improvement specifically in the verbal subtests of the NIH Toolbox, coupled with parent rating of improvements, particularly in language.”

Cognitive assessments using the NIH Toolbox revealed significant benefit in oral reading recognition, picture vocabulary and the cognition crystallized composite score. Parent/caregiver ratings revealed benefit that was judged to be clinically significant in language and daily functioning.

After 12 weeks of treatment in the study, patients crossed over and took placebo if they had been taking drug, and drug if they had been taking placebo for another 12 weeks. The benefit of BPN14770 was found to persist up to 12 weeks after the crossover from drug to placebo. BPN14770 was very well tolerated, with few adverse events.

In laboratory studies, BPN14770 promoted the maturation of connections between neurons, (which is impaired in patients with fragile X syndrome). BPN14770 is being developed by Tetra Therapeutics for the treatment of fragile X syndrome. The drug’s mechanism of action also may have potential to improve cognitive and memory function in Alzheimer’s disease and other dementias, learning/developmental disabilities and schizophrenia. At this time, however, the U.S. Food and Drug Administration only has approved BPN14770 for investigational use, and it will be important to do larger controlled studies in fragile X syndrome to confirm the cognitive benefit of the drug.

Reference: Rush University Medical Centre. “Treatment found to improve cognitive function in patients with fragile X syndrome: Results from phase two study show improved language and daily functioning among participants.” ScienceDaily. ScienceDaily, 29 April 2021. www.sciencedaily.com/releases/2021/04/210429142643.htm

The study is published in a special issue on air pollution in the Journal of the American Heart Association, an open access journal of the American Heart Association.

Other studies look at: the effects of diesel exhaust on the muscle sympathetic nerve; the impact of pollutants on high blood pressure; rates of hospital readmission for heart failure among those exposed to high levels of ambient air pollution; and risk of stroke and heart attack after long-term exposure to high levels of particulate matter. The studies include health outcomes of people who were exposed to pollutants in the United States, China and Europe.

High blood pressure during childhood and adolescence is a risk factor for hypertension and heart disease in adulthood. Studies on air pollution and blood pressure in adolescents and children, however, have produced inconsistent conclusions. This systematic review and meta-analysis pooled information from 14 studies focused on the association between air pollution and blood pressure in youth. The large analysis included data for more than 350,000 children and adolescents (mean ages 5.4 to 12.7 years of age).

“Our analysis is the first to closely examine previous research to assess both the quality and magnitude of the associations between air pollution and blood pressure values among children and adolescents,” said lead study author Yao Lu, M.D., Ph.D., professor of the Clinical Research Center at the Third Xiangya Hospital at Central South University in Changsha, China, and professor in the department of life science and medicine at King’s College London. “The findings provide evidence of a positive association between short- and long-term exposure to certain environmental air pollutants and blood pressure in children and adolescents.”

The analysis included 14 studies published through September 6, 2020, exploring the impact of long-term exposure (?30 days) and/or short-term exposure (<30 days) of ambient air pollution on blood pressure levels of adolescents and/or children in China and/or countries in Europe.

The studies were divided into groups based upon length of exposure to air pollution and by composition of air pollutants, specifically nitrogen dioxide and particulate matter with diameter ?10 μm or ?2.5 μm. (The majority of research linking heart disease with particulate matter focuses on particle matter mass, which is categorized by aerodynamic diameter – μm or PM.) Fine particles are defined as PM2.5 and larger; coarse particles are defined at PM10; and the concentrations of particulate matter are typically measured in their mass per volume of air (μg/m3).

The meta-analysis concluded:

• Short-term exposure to PM10 was significantly associated with elevated systolic blood pressure in youth (the top number on a blood pressure reading).
• Periods of long-term exposure to PM2.5, PM10 and nitrogen dioxide were also associated with elevated systolic blood pressure levels.
• Higher diastolic blood pressure levels (the bottom number on a blood pressure reading) were associated with long-term exposure to PM2.5 and PM10.

“To reduce the impact of environmental pollution on blood pressure in children and adolescents, efforts should be made to reduce their exposure to environmental pollutants,” said Lu. “Additionally, it is also very important to routinely measure blood pressure in children and adolescents, which can help us identify individuals with elevated blood pressure early.”

The results of the analysis are limited to the studies included, and they did not include data on possible interactions between different pollutants, therefore, the results are not generalizable to all populations. Additionally, the analysis included the most common and more widely studied pollutants vs. air pollutants confirmed to have heart health impact, of which there are fewer studies.

Reference: https://newsroom.heart.org/news/air-pollution-linked-to-high-blood-pressure-in-children-other-studies-address-air-quality-and-the-heart?preview=21700d0a86c1830864668eda0f74acb4

The findings, from Imperial College London and the University of Texas, may also reveal a potential way to make the antibiotic more powerful.

The antibiotic colistin has become a last resort treatment for infections caused by some of the world’s nastiest superbugs. However, despite being discovered over 70 years ago, the process by which this antibiotic kills bacteria has, until now, been something of a mystery.

Now, researchers have revealed that colistin punches holes in bacteria, causing them to pop like balloons. The work, funded by the Medical Research Council and Wellcome Trust, and published in the journal eLife, also identified a way of making the antibiotic more effective at killing bacteria.

Colistin was first described in 1947, and is one of the very few antibiotics that is active against many of the most deadly superbugs, including E. coli, which causes potentially lethal infections of the bloodstream, and Pseudomonas aeruginosa and Acinetobacter baumannii, which frequently infect the lungs of people receiving mechanical ventilation in intensive care units.

These superbugs have two ‘skins’, called membranes. Colistin punctures both membranes, killing the bacteria. However, whilst it was known that colistin damaged the outer membrane by targeting a chemical called lipopolysaccharide (LPS), it was unclear how the inner membrane was pierced.

Now, a team led by Dr Andrew Edwards from Imperial’s Department of Infectious Disease, has shown that colistin also targets LPS in the inner membrane, even though there’s very little of it present.

Dr Edwards said: “It sounds obvious that colistin would damage both membranes in the same way, but it was always assumed colistin damaged the two membranes in different ways. There’s so little LPS in the inner membrane that it just didn’t seem possible, and we were very sceptical at first. However, by changing the amount of LPS in the inner membrane in the laboratory, and also by chemically modifying it, we were able to show that colistin really does puncture both bacterial skins in the same way – and that this kills the superbug. ”

Next, the team decided to see if they could use this new information to find ways of making colistin more effective at killing bacteria.

They focussed on a bacterium called Pseudomonas aeruginosa, which also causes serious lung infections in people with cystic fibrosis. They found that a new experimental antibiotic, called murepavadin, caused a build up of LPS in the bacterium’s inner skin, making it much easier for colistin to puncture it and kill the bacteria.

The team say that as murepavadin is an experimental antibiotic, it can’t be used routinely in patients yet, but clinical trials are due to begin shortly. If these trials are successful, it may be possible to combine murepavadin with colistin to make a potent treatment for a vast range of bacterial infections.

Akshay Sabnis, lead author of the work also from the Department of Infectious Disease, said: “As the global crisis of antibiotic resistance continues to accelerate, colistin is becoming more and more important as the very last option to save the lives of patients infected with superbugs. By revealing how this old antibiotic works, we could come up with new ways to make it kill bacteria even more effectively, boosting our arsenal of weapons against the world’s superbugs.”

http://www3.imperial.ac.uk/college/news 

IMAGE: THE SUPERBUG PSEUDOMONAS AERUGINOSA, WHICH CAN CAUSE LUNG INFECTIONS IN PEOPLE ON VENTILATORS IN INTENSIVE CARE UNITS. view more 

CREDIT: IMPERIAL COLLEGE LONDON

Loneliness and social isolation have been major problems for many under lockdown, and for older people in particular. Loneliness raises risk of depression and other negative health outcomes. In a paper published in the journal Healthcare, researchers from Surrey investigated whether more frequent internet use in older people helped reduce this risk.

Researchers studied 3,491 individual participants drawn from the English Longitudinal Study of Ageing in Summer 2020, whilst social distancing measures were in place across the country. Participants were surveyed on the frequency and type of their internet usage – such as information searching or for communication purposes.

Those who reported using the internet frequently (once a day or more) had much lower levels of depression symptoms and reported higher quality of life compared to those who used the internet only once a week or less. Using the internet for communication was particularly linked to these beneficial effects, suggesting that going online to stay connected with friends and family helped combat the negative psychological effects of social distancing and lockdown in adults aged 55-75.

Conversely, the study found that people who mostly used the internet to search for health-related information reported higher levels of depression symptoms. This might be due to a greater degree of worry triggered by reading Covid-19 and other health-related internet sources.

Dr Simon Evans, Lecturer in Neuroscience at the University of Surrey, said: “As social restrictions continue during the Covid-19 pandemic, older people are at greater risk of loneliness and mental health issues. We found that older adults who used the internet more frequently under lockdown, particularly to communicate with others, had lower depression scores and an enhanced quality of life. As the Covid-19 situation evolves, more frequent internet use could benefit the mental health of older people by reducing loneliness and risk of depression, particularly if further lockdowns are imposed in the future.”

UW Medicine and University of Oxford doctors led this first-of-its-kind study, published today in JAMA Pediatrics. The investigation involved more than 100 researchers and pregnant women from 43 maternity hospitals in 18 low-, middle- and high-income nations; 220 of the women received care in the United States, 40 at UW Medicine. The research was conducted between April and August of 2020.

The study is unique because each woman affected by COVID-19 was compared with two uninfected pregnant women who gave birth during the same span in the same hospital.

Aside from an increased risk of death, women and their newborns were also more likely to experience preterm birth, preeclampsia and admission to the ICU and/or intubation. Of the mothers who tested positive for the disease, 11.5% of their babies also tested positive, the study found.

Although other studies have looked at COVID-19’s effects on pregnant women, this is among the first study to have a concurrent control group with which to compare outcomes, said Dr. Michael Gravett, one of the study’s lead authors.

“The No. 1 takeaway from the research is that pregnant women are no more likely to get COVID-19, but if they get it, they are more likely to become very ill and more likely to require ICU care, ventilation, or experience preterm birth and preeclampsia,” he said. Gravett is a professor of obstetrics and gynecology at the University of Washington School of Medicine. Co-investigator Dr. Lavone Simmons is a UW acting assistant professor of OB-GYN.

One caveat, Gravett noted, was that women whose COVID-19 was asymptomatic or mild were not found to be at increased risk for ICU care, preterm birth or preeclampsia. About 40% of the women in this study were asymptomatic. Pregnant women who were obese or had hypertension or diabetes were at the greatest risk for severe disease, the findings showed.

Babies of the women infected with COVID-19 were more likely to be born preterm; but their infections were usually mild, the study found. Breastfeeding seemed not to be related to transmitting the disease. Delivery by Caesarean section, however, might be associated with an increased risk of having an infected newborn, the study found.

Gravett suggested that these and parallel research findings compelled U.S. states’ decisions to open vaccine eligibility to pregnant women – who were initially considered a population at low risk for severe COVID-19.

“I would highly recommend that all pregnant women receive the COVID-19 vaccines,” based on this research, he said.

The study demonstrates the importance of collecting large-scale, multinational data quickly during a health crisis, Gravett said. Researchers were able to complete the investigation and report findings in only nine months, using infrastructure already in place from the INTERGROWTH-21st Project, which emerged in 2012 to study fetal growth and neonatal outcomes.