Immune-regulating brain cells known as microglia are known to play a role in the progression of Alzheimer’s disease (AD). A new study by investigators from Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, explores how the genetics of microglia contribute to neuroinflammation and, in turn, AD. The team revealed that a reduction of INPP5D, a gene found in microglia, results in neuroinflammation and increases the risk for AD. Their results, which have important implications for the design of microglia-centered therapeutics for Alzheimer’s disease and related disorders, are published in Nature Communications.

“We know that microglia play important roles in the healthy and diseased brain, but, in many cases the molecular mechanisms underlying this relationship are poorly understood,” said corresponding author Tracy Young-Pearse, PhD, from the Department of Neurology at Brigham and Women’s Hospital. “If we’re able to identify and understand the significance of specific genes that play a role in neuroinflammation, we can more readily develop effective, targeted therapeutics.”

Neuroinflammation is important to monitor in people with neurodegenerative diseases, but it can be difficult to detect, especially in the early stages of AD. The earlier neurologists can identify it, the earlier they can treat it. Microglia are clearly involved in the process of neuroinflammation, but there are many unanswered questions regarding the molecular pathways involved.

The team used a variety of experimental approaches to probe the relationship between levels of INPP5D and a specific type of brain inflammation, activation of the inflammasome. As part of their study, the team compared human brain tissue from patients with AD and a control group. They found lower levels of INPP5D in the tissues of patients with AD and when INPP5D was reduced, it activated inflammation. In parallel, they used living human brain cells derived from stem cells to study the intricate molecular interactions within microglia that mediate inflammatory processes with a reduction of INPP5D. These studies identified specific proteins that could be inhibited to block inflammasome activation in microglia.

Although the team’s work represents the most comprehensive analysis of INPP5D in the AD brain, it remains to be determined whether INPP5D should be targeted with therapeutics. The team notes that their findings suggest INPP5D activity in AD brains is complex and future studies are needed to understand if INPP5D can be targeted to prevent cognitive decline in patients with AD.

“Our results highlight an exciting promise for INPP5D, but some questions still remain,” said Young-Pearse. “Future studies examining the interaction between INPP5D activity and inflammasome regulation are essential to improve our understanding of microglia in AD and to help develop a comprehensive toolbox of therapeutics that can be deployed to treat each of the molecular roads that lead to AD.”

The University of Bristol team, led by Professor Bruce Drinkwater and Professor Anthony Croxford, developed approach was used to review a long steel pipe with multiple defects, including circular holes with different sizes, a crack-like defect and pits, through a designed inspection path to achieve 100% detection coverage for a defined reference defect.

In the study, published today in NDT and E International, they show how they were able to effectively examine large plate-like structures using a network of independent robots, each carrying sensors capable of both sending and receiving guided acoustic waves, working in pulse-echo mode.

This approach has the major advantage of minimizing communication between robots, requires no synchronization and raises the possibility of on-board processing to lower data transfer costs and hence reducing overall inspection expenses. The inspection was divided into a defect detection and a defect localization stage.

Lead author Dr Jie Zhang explained: “There are many robotic systems with integrated ultrasound sensors used for automated inspection of pipelines from their inside to allow the pipeline operator to perform required inspections without stopping the flow of product in the pipeline. However, available systems struggle to cope with varying pipe cross-sections or network complexity, inevitably leading to pipeline disruption during inspection. This makes them suitable for specific inspections of high value assets, such as oil and gas pipelines, but not generally applicable.

“As the cost of mobile robots has reduced over recent years, it is increasingly possible to deploy multiple robots for a large area inspection. We take the existence of small inspection robots as its starting point, and explore how they can be used for generic monitoring of a structure. This requires inspection strategies, methodologies and assessment procedures that can be integrated with the mobile robots for accurate defect detection and localization that is low cost and efficient.

“We investigate this problem by considering a network of robots, each with a single omnidirectional guided acoustic wave transducer. This configuration is considered as it is arguably the simplest, with good potential for integration in a low cost platform.”

The methods employed are generally applicable to other related scenarios and allow the impact of any detection or localization method decisions to be quickly quantified. The methods could be used across other materials, pipe geometries, noise levels or guided wave modes, allowing the full range of sensor performance parameters, defects sizes and types and operating modalities to be explored. Also the techniques can be used to assess the detection and localization performance for specified inspection parameters, for example, predict the minimum detectable defect under a specified probability of detection and probability of false alarm.

The team will now investigate collaboration opportunities with industries to advance current prototypes for actual pipe inspections. This work is funded by the UK’s Engineering and Physical Sciences Research Council (EPSRC) as a part of the Pipebots project.

Written by a panel of U.S. and international experts on the psychology of misinformation, the report outlines the processes that make people susceptible to misinformation and offers solutions to combat it.

People are more likely to believe misinformation if it comes from groups they belong to or if they judge the source as credible, according to the report “Using Psychological Science to Understand and Fight Health Misinformation: An APA Consensus Statement.” It defines misinformation as “any information that is demonstrably false or otherwise misleading, regardless of its source or intention.”

The report outlines the key features of misinformation that fool people into believing and spreading it. For instance, it found that people are more likely to believe false statements that appeal to emotions such as fear and outrage. They are also more likely to believe misinformation that paints groups that they view as “others” in a negative light. And people are more likely to believe information the more it is repeated, even when it contradicts their prior knowledge. These findings suggest that it is important to stop misinformation early, the report says.

The report also describes features of social media that help misinformation spread very quickly. “Rapid publication and peer-to-peer sharing allow ordinary users to distribute information quickly to large audiences, so misinformation can be policed only after the fact (if at all),” the report says. “‘Echo chambers’ bind and isolate online communities with similar views, which aids the spread of falsehoods and impedes the spread of factual corrections.”

As a result, “most online misinformation originates from a small minority of ‘superspreaders,’ but social media amplifies their reach and influence.”

There are two levels on which misinformation can be stopped, according to the report: systemic approaches, such as legislation and technology standards, and individual approaches focused on changing individual behaviors. The latter include:

• fact-checking, or debunking;
• prebunking, or pre-emptive debunking to prevent people from falling for misinformation in the first place;
• nudges, such as asking people to consider the accuracy of information before sharing it, or rewarding people to be as accurate as possible;
• and formal education or community outreach to raise people’s awareness about healthy online behavior and media use.

The report acknowledges that there is much more to learn and recommends more research funding and industry cooperation to understand behaviors related to misinformation and create tools to correct it. The panel members who wrote the report spent more than a year reviewing the scientific literature to develop their recommendations. The report was commissioned by the Centers for Disease Control and Prevention and funded as part of a $2 million grant to develop effective solutions to COVID-19 vaccine hesitancy.

While the panel’s recommendations focus on health misinformation, they can also be used for broader topics such as politics and climate change. For instance, these findings offer direct input to one of the main issues highlighted in APA’s Health Advisory on Social Media by addressing tactics that can be used to combat misinformation.

The report recommends eight steps for policymakers, scientists, media and the public to help curb the spread of misinformation and the risks it poses to health, well-being and civic life:

1. Avoid repeating misinformation without including a correction.
2. Collaborate with social media companies to understand and reduce the spread of harmful misinformation.
3. Use misinformation correction strategies with tools already proven to promote healthy behaviors.
4. Leverage trusted sources to counter misinformation and provide accurate health information.
5. Debunk misinformation often and repeatedly using evidence-based methods.
6. Prebunk misinformation to inoculate susceptible audiences by building skills and resilience from an early age.
7. Demand data access and transparency from social media companies for scientific research on misinformation.
8. Fund basic and translational research into the psychology of health misinformation, including ways to counter it.

“These psychological science findings help to explain how misinformation enters our thought processes,” the report states. “It is effortful and difficult for our brains to apply existing knowledge when encountering new information; when new claims are false but sufficiently reasonable, we can learn them as facts. Thus, everyone is susceptible to misinformation to some degree: we acquire it even when we know better.”

Despite the existence of vaccines against pneumococcal infections such as otitis media, sinusitis, and meningitis, the prevalence of pneumococcal pneumonia remains high. Currently, around 100 new serotypes of Streptococcus pneumoniae have been identified, and the increase in pneumococcal infections caused by serotypes not covered by the vaccine has become a concern. This situation underscores the need for a more versatile vaccine.

Building on their previous success in mucosal responses in 2019, in which they developed a mucosal vaccine that caninduce antigen-specific mucosal immune responses, mainly immunoglobulin A (IgA), on the target mucosal surface, a research team led by Professor Satoshi Uematsu and Associate Professor Kosuke Fujimoto from the Department of Immunology and Genomics at the Graduate School of Medicine, Osaka Metropolitan University, has this time set out to bridge the gap in pneumococcal pneumonia vaccination efficacy.

To successfully develop a novel pneumococcal vaccine, the research team combined its proprietary mucosal vaccine technology with pneumococcal surface proteins that can cover a wide range of serotypes. Experiments conducted on mice and macaques have demonstrated the vaccine’s efficacy in suppressing pneumococcal pneumonia in the target animal groups.

“This research has succeeded in developing a vaccine formulation that can potentially be used in humans, which will advance the development of this vaccine for clinical applications,” said Professor Fujimoto. “This next-generation vaccine technology is expected to contribute to the treatment of infectious diseases in the future.”