Eating disorders and especially obesity are one of the most common causes of a variety of diseases in industrialized societies worldwide, especially cardiovascular diseases with permanent disabilities or fatal outcomes such as heart attacks, diabetes, or strokes. The Robert Koch Institute reported in 2021 that 67 per cent of men and 53 percent of women in Germany are overweight. 23 per cent of adults are severely overweight (obese). Attempts to influence eating behaviour with medication have so far proved ineffective. A novel therapy that modulates the excitability of networks that control eating behaviour would be a decisive step towards controlling this widespread obesity.

The research team found an increased rate of obesity and the attendant type II diabetes in people with impaired synaptic LPA signalling. A group led by Professor Johannes Vogt (Faculty of Medicine, University of Cologne), Professor Robert Nitsch (Faculty of Medicine, University of Münster) und Professor Thomas Horvath (Yale School of Medicine, New Haven, USA) has now shown that control of the excitability of neurons in the cerebral cortex by LPA plays an essential role in the control of eating behaviour: AgRP neurons regulate the amount of lysophosphatidylcholine (LPC) in the blood. Through active transport, LPC reaches the brain, where it is converted by the enzyme autotaxin (ATX) into LPA, which is active at the synapse. Synaptic LPA signals stimulate specific networks in the brain, thus leading to increased food intake.

In the mouse model, after a period of fasting an increase in LPC in the blood led to an increase in stimulating LPA in the brain. These mice showed typical food-seeking behaviour. Both could be normalized by administrating autotaxin inhibitors. Obese mice, on the other hand, lost weight when these inhibitors were administered continuously. Johannes Vogt explained: ‘We saw a significant reduction in excessive food intake and obesity through gene mutation and pharmacological inhibition of ATX. Our fundamental findings on the LPA-controlled excitability of the brain, which we have worked on for years, therefore also play a central role for eating behaviour.’ Robert Nitsch sees the findings as an important step towards new drug development: ‘The data show that people with a disturbed synaptic LPA signalling pathway are more likely to be overweight and suffer from type II diabetes. This is a strong indication of a possible therapeutic success of ATX inhibitors, which we are currently developing together with the Hans Knöll Institute in Jena for use in humans.’

These findings on the excitation control of neuronal networks in eating behaviour through lysophospholipids and the new therapeutic possibilities they suggest could in future contribute not only to treating eating disorders, but also neurological and psychiatric illnesses.

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The finding is the first measurement of how much hydroxymethanesulfonate, or HMS, is in Fairbanks’ air.

The compound constituted 3% to 7% of the total amount of particles less than 2.5 micrometers, or PM 2.5, during pollution episodes. That amount is substantially higher than observed elsewhere, leading the research team to conclude that Fairbanks’ extreme low temperatures are a factor in the compound’s formation.

“People in the community really are not aware of this,” said Jingqiu Mao, principal investigator on the research. “We feel it’s important to inform the community about this new chemical compound in Fairbanks.”

“Very little is known about the health impact of hydroxymethanesulfonate,” he said. “This compound is new to us in the atmospheric chemistry and air quality communities. We didn’t know this compound could be so abundant.”

The research was published in May in Environmental Science & Technology and authored by James Campbell, a graduate student of Mao’s. The work included scientists from the University of Alaska Fairbanks Geophysical Institute, Georgia Institute of Technology, Johns Hopkins University and NASA’s Goddard Space Flight Center.

The research paper is the first produced under a three-year National Science Foundation grant.

Fairbanks has been under mandate by the U.S. Environmental Protection Agency to improve its wintertime air quality and has been working for years to do so. The community and state face penalties for noncompliance.

The new HMS finding is also significant because recent studies have revealed that hydroxymethanesulfonate can easily be mistaken for sulfate, potentially making prior air pollution measurements inaccurate. Studying HMS also enables a better understanding of other chemical reactions in ambient aerosols in Fairbanks’ winter months.

Knowing the correct makeup of the fine particulate matter pollution is key to implementing appropriate air quality control measures, Mao said.

“A lot of sources contribute to PM 2.5,” he said. “But when you start thinking about improving air quality, which part should be dealt with first? And what are the consequences of that?”

The research team studied Fairbanks’ air in two winters: January to March 2020 and December 2020 to February 2021. Data came from instruments placed near the UAF Community and Technical College in downtown Fairbanks and at a nearby state Department of Environmental Conservation site already measuring total PM2.5, sulfur dioxide and temperature.

Scientists have known that hydroxymethanesulfonate forms through the combination of sulfur dioxide and formaldehyde, which combine when they are attracted to liquid particles in the atmosphere.

Scientists don’t know, however, to what extent factors such as the acidity of the atmospheric droplets, temperature and humidity lead to HMS formation.

They also don’t know which source is most responsible for HMS formation in Fairbanks. Sulfur dioxide comes from combustion of fossil fuels, including heating oil and coal. Formaldehyde likely gets into the air from burning wood.

Studies have shown that wood smoke contributes 40% to 70% to the wintertime PM2.5 mass concentration in Fairbanks.

“Fairbanks is one of the few optimal places for HMS formation,” Mao said. “And that is not necessarily a good thing.”

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Materials provided by University of Alaska Fairbanks. Original written by Rod Boyce. Note: Content may be edited for style and length.

Now a new review study has found acetaminophen is safe in older adults, but non-steroidal anti-inflammatories (ibuprofen) may be more effective for spine-related pain. Non-steroidal anti-inflammatories should be used short-term in lower dose courses with gastrointestinal precaution while corticosteroids show the least evidence for treating nonspecific back pain.

Additionally, nerve pain medications (gabapentin and pregabalin) can be used in older persons, with caution to dose and kidney function. Newer antidepressants (duloxetine) more so than older ones (nortriptyline) can help with spine-related pain, with attention to possible sedation and dizziness. Some muscle relaxants (baclofen and tizanidine) can be used in older persons, again accounting for kidney and liver function. Opioids have limited use in common spine-related pain, but can be used with caution in cases that don’t respond to treatment.

“Most older people experience neck or low back pain at some point, bothersome enough to see their doctor. Our findings provide a helpful medication guide for physicians to use for spine pain in an older population that can have a complex medical history,” explained corresponding author Michael D. Perloff, MD, PhD, assistant professor of neurology at Boston University School of Medicine (BUSM) and a neurologist at Boston Medical Center.

The researchers performed a literature review to assess the evidence-basis for medications used for spine-related pain in older adults, with a focus on drug metabolism and adverse drug reactions. They then provided their recommendations based on safe and effective dosing.

Among their findings:

• Pain medicines gabapentin and pregabalin may cause dizziness or difficulty walking, but may have some benefit for neck and back nerve pain (such as sciatica) in older adults. They should be used in lower doses with smaller dose adjustments.
• Some muscle relaxants (carisoprodol, chlorzoxazone, cyclobenzaprine, metaxalone, methocarbamol, and orphenadrine) are avoided in older adults due to risk for sedation and falls. Others (tizanidine, baclofen, dantrolene) may be helpful for neck and back pain, with the most evidence for tizanidine and baclofen. These should be used in reduced doses, avoiding tizanidine with liver disease and reducing baclofen dosing with kidney disease.
• Older antidepressants are typically avoided in older adults due to their side effects, but nortriptyline and desipramine may be better tolerated for neck and back nerve pain at lower doses. Overall, newer antidepressants (namely duloxetine) have a better safety profile and good efficacy for spine-related nerve pain.
• Tramadol may be tolerated in older adults, but has risk for sedation, upset stomach, and constipation. It may be used in lower doses after alternative medications have failed and works well with co-administered acetaminophen. Opioids are avoided due to their side effects and mortality risk, but low dose opioid therapy may be helpful for severe refractory pain with close monitoring of patients clinically.

According to the researchers, complementary medicine, physical therapy, injections and surgery all have a place to help older persons with spine-related pain. “Medications used at the correct dose, for the correct diagnosis, adjusting for preexisting medical problems can result in better use of treatments for spine pain,” added first author Jonathan Fu, a 2022 MD graduate from BUSM.

These findings appear online in the journal Drugs & Aging.

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Engineers at Rice University have developed a method that allows humans to help robots “see” their environments and carry out tasks.

The strategy called Bayesian Learning IN the Dark — BLIND, for short — is a novel solution to the long-standing problem of motion planning for robots that work in environments where not everything is clearly visible all the time.

The peer-reviewed study led by computer scientists Lydia Kavraki and Vaibhav Unhelkar and co-lead authors Carlos Quintero-Peña and Constantinos Chamzas of Rice’s George R. Brown School of Engineering was presented at the Institute of Electrical and Electronics Engineers’ International Conference on Robotics and Automation in late May.

The algorithm developed primarily by Quintero-Peña and Chamzas, both graduate students working with Kavraki, keeps a human in the loop to “augment robot perception and, importantly, prevent the execution of unsafe motion,” according to the study.

To do so, they combined Bayesian inverse reinforcement learning (by which a system learns from continually updated information and experience) with established motion planning techniques to assist robots that have “high degrees of freedom” — that is, a lot of moving parts.

To test BLIND, the Rice lab directed a Fetch robot, an articulated arm with seven joints, to grab a small cylinder from a table and move it to another, but in doing so it had to move past a barrier.

“If you have more joints, instructions to the robot are complicated,” Quintero-Peña said. “If you’re directing a human, you can just say, ‘Lift up your hand.'”

But a robot’s programmers have to be specific about the movement of each joint at each point in its trajectory, especially when obstacles block the machine’s “view” of its target.

Rather than programming a trajectory up front, BLIND inserts a human mid-process to refine the choreographed options — or best guesses — suggested by the robot’s algorithm. “BLIND allows us to take information in the human’s head and compute our trajectories in this high-degree-of-freedom space,” Quintero-Peña said.

“We use a specific way of feedback called critique, basically a binary form of feedback where the human is given labels on pieces of the trajectory,” he said.

These labels appear as connected green dots that represent possible paths. As BLIND steps from dot to dot, the human approves or rejects each movement to refine the path, avoiding obstacles as efficiently as possible.

“It’s an easy interface for people to use, because we can say, ‘I like this’ or ‘I don’t like that,’ and the robot uses this information to plan,” Chamzas said. Once rewarded with an approved set of movements, the robot can carry out its task, he said.

“One of the most important things here is that human preferences are hard to describe with a mathematical formula,” Quintero-Peña said. “Our work simplifies human-robot relationships by incorporating human preferences. That’s how I think applications will get the most benefit from this work.”

“This work wonderfully exemplifies how a little, but targeted, human intervention can significantly enhance the capabilities of robots to execute complex tasks in environments where some parts are completely unknown to the robot but known to the human,” said Kavraki, a robotics pioneer whose resume includes advanced programming for NASA’s humanoid Robonaut aboard the International Space Station.

“It shows how methods for human-robot interaction, the topic of research of my colleague Professor Unhelkar, and automated planning pioneered for years at my laboratory can blend to deliver reliable solutions that also respect human preferences.”

Rice undergraduate alumna Zhanyi Sun and Unhelkar, an assistant professor of computer science, are co-authors of the paper. Kavraki is the Noah Harding Professor of Computer Science and a professor of bioengineering, electrical and computer engineering and mechanical engineering, and director of the Ken Kennedy Institute.

The National Science Foundation (2008720, 1718487) and an NSF Graduate Research Fellowship Program grant (1842494) supported the research.

Video: https://youtu.be/RbDDiApQhNo

Their findings were recently published in the International Society for Microbial Ecology Journal.

Humans rely on honey bees for food security. Because they will pollinate almost anything, honey bees are extremely useful for agriculture. But over the past few decades, the honey bee population has experienced dramatic declines caused by the effects of multiple stressors, the most pervasive of which is limited nutrition. Beekeepers in the United States reported losing 40.5 percent of their managed colonies between 2015 and 2016 alone, according to a national survey.

“The effects of poor nutrition are most damaging in the developing larvae of honey bees, who mature into workers unable to meet the needs of their colony,” said Irene Newton, a professor in the IU Bloomington College of Arts and Sciences’ Department of Biology, who led the study. “It is therefore essential that we better understand the nutritional landscape experienced by honey bee larvae.”

Newton said honey bees need to collect pollen and nectar from a variety of plants and flowers to help their colonies stay healthy throughout the year. But many bees in the U.S. lack this floral diversity.

“We’ve changed the way we use our land in the U.S.,” Newton said. “Now we have tons of monoculture crops like corn, which are wind pollinated and therefore no use to bees, covering acres and acres of land. Other crops that bees do pollinate are grown in monoculture as well, limiting the options for bees.

“If you limit yourself to only eating one thing, that’s not healthy for you. You have to have a broad diet that will help fulfill all of your nutritional needs. Bees are the same way.”

Honey bee larvae are fed by their sister bees. Their diet consists of foraged ingredients such as nectar and pollen, as well as royal jelly — a bee glandular secretion that is complex and nutrient rich. If larvae are destined to be queens, they will eat royal jelly their whole lives. If they are workers, their diets will shift to nectar and pollen after a few days.

In addition to being more nutritious than nectar and pollen, royal jelly has long been known to possess potent antimicrobial properties due to its acidity, viscosity and the presence of antimicrobial peptides. This means that most microbes exposed to royal jelly die, Newton said.

Except one.

According to their new study, Newton and her research team found that a specific microbe — Bombella apis — is the only larva-associated bacterium that’s actually able to thrive in royal jelly. They also found that B. apis makes royal jelly more nutritious by significantly increasing its amino acid content, which helps developing bees build resilience against nutritional stress.

“We have identified a nutritional symbiont of honey bees — a microbe that can help bolster the bees against nutrient scarcity and stress,” Newton said. “When we limited bee nutrition during development, we saw a drop in mass for the bees; bees were much smaller than their control counterparts.

“When B. apis was added to these same bees, although they had poor nutrition, they reached the same mass as control bees given full nutrition. The microbe was able to make up for the poor diet. This suggests that B. apis could be added to colonies as a probiotic to protect from nutritional stress.”

The results suggest that B. apis may have potential as a key supplement in future beekeepers’ efforts to counteract the negative influence of poor nutrition on honey bee health. B. apis can survive for over 24 hours in sugar water, so beekeepers who are already supplementing their colonies could potentially integrate a B. apis probiotic into their bees’ diets.

This research expands on over six years of previous studies by Newton and her colleagues, including findings that B. apis protects bees against fungal infections and is a significant part of the queen gut microbiome.

“We are excited to explore the other interactions that B. apis has in a colony, to better understand what it’s doing in different environments and the role it plays in association with honey bee queens,” Newton said.