Publisher Health

At a Biotechnology Council event a few years ago, Nicole Valenzuela’s ears perked up when she heard what a group of researchers in Iowa State University’s College of Veterinary Medicine had in the works: a method for creating a lab-grown, simplified mimic of dog intestines.
“I told them, ‘Oh! I want to do that but with turtles. Is it doable?” said Nicole Valenzuela, professor of ecology, evolution and organismal biology at Iowa State.
It is indeed doable, new research from a team led by Valenzuela shows. The three-dimensional clusters grown from adult stems cells are called organoids and are designed to assist in research. In a paper published Feb. 22 in Communications Biology, a peer-reviewed journal, Valenzuela and her colleagues describe their creation of organoids that mimic a liver from three species of turtles. It’s the first set of organoids developed for turtles and only the second for any reptile.
Studying turtle genetics with a liver organoid should speed up research to uncover the cause of turtle traits that could potentially have medical applications for humans — the ability of painted turtles to survive weeks without oxygen and withstand extreme cold, for instance.
“Some of their unique adaptations make painted turtles an interesting model for biomedicine. But they remain understudied because it’s difficult work to do. The idea here is to eliminate that bottleneck,” Valenzuela said.
Benefits of organoids
Valenzuela has been researching turtles for more than three decades, drawn to study these animals because of their temperature-dependent sex determination. In many turtles, colder eggs are more likely to produce males, while a warmer nest brings more females.

In studying the genetic causes of traits, biologists eventually need to validate their findings to confirm a gene is functioning as suspected. That requires manipulating those genes, which is a challenge with turtles because they reproduce seasonally and mature slowly, Valenzuela said.
“It’s easy when you’re working with fruit flies or flatworms, but doing transgenic experiments on turtles is pretty much impossible,” she said.
That’s part of why researchers are increasingly developing organoids, she said. The species- and organ-specific mimics expand the range for modern gene editing, allowing scientists to devote more attention to animals that are promising research targets but challenging to study.
“From a single chunk of tissue, you can have an unlimited source of experiment subjects and don’t have to sample animals constantly. Organoids are an important technology for reducing live animal research,” Valenzuela said.
Tweaking the recipe
Valenzuela’s team built their process on the methods used by the research group in the College of Veterinary Medicine, whose work on organoids included a canine intestinal model for testing drug absorption rates. The leads on the canine intestine project — Karin Allenspach and Jon Mochel, now at the University of Georgia — also were part of the turtle organoid project. Recent ISU doctoral graduate Christopher Zdyrski was the first author on the turtle organoid paper.

Organoids are made by culturing a tissue sample in a solution that stimulates production of stem cells, the special cells within a body responsible for repair and growth. Given the right fuel, turtle liver stem cells start making turtle liver cells. The microscopic ball of cells is hollow at first but less so as cells accumulate, Valenzuela said. A three-dimensional cluster is better than a flat layer of single cells at mimicking the complexity of actual tissue, even if not fully.
Valenzuela said her team chose to focus first on the liver because it plays a critical role in helping turtles survive extreme cold and oxygen deprivation. The liver produces proteins and enzymes to boost cellular defenses against freezing and provides the small amount of energy a turtle needs for anaerobic metabolism to survive without oxygen, using their shells and bones to manage the resulting lactic acid build-up.
Applying a process designed for dog intestines to a different organ in a different animal took some modification but not necessarily an overhaul, similar to swapping out ingredients in a recipe, she said.
“All of the discovery is in developing those protocols and in characterizing how similar the organoids are to the original liver tissue,” she said.
What’s next
Organoids generated by Valenzuela’s team came from samples collected in Iowa from juvenile spiny softshell and snapping turtles as well as juvenile, adult and embryonic painted turtles. Seeing success across multiple species and developmental stages suggests the techniques could be replicated broadly, she said.
Valenzuela’s group is already at work on creating organoids from turtle gonads, to further investigate the underlying causes of sex determination. They’re also seeking grant funding to study oxygen deprivation and resistance to cold using the novel turtle liver organoids.
But given the lack of genomic tools for studying reptiles — the only other known reptilian organoid is from snake venom glands, the researchers reported in their paper — Valenzuela is optimistic that her team’s work will be used by herpetologists to expand their research.
“That’s the hope, that other scientists adopt these protocols to study other reptiles,” she said.

A novel screening system developed at Kyoto University enables researchers to investigate sperm cell development and health at the molecular level. The new approach, published in Cell Genomics, promises breakthroughs in male contraception and infertility treatments.
The study, led by Professor Jun Suzuki of the Institute for Integrated Cell-Material Sciences (iCeMS), addresses a critical gap by directly targeting genes within testicular cells inside living organisms. Utilizing a genetic tool called CRISPR, which can be likened to genetic scissors, the researchers developed a method to investigate which genes contribute to healthy sperm production in living animals. Until now, this had mainly been done in cells cultivated in the laboratory. The researchers randomly disrupted genes by developing a method to introduce a collection of genetic tools in lentivirus into testicular cells in testes at high efficiency. Through this method, the researchers made it possible to analyze the effects of targeted genes on specific biochemical reactions in the sperm cells, such as the movement of lipids (fats) in cell membranes.
Using the method, the team focused on sperms with defective capacitation, a process through which sperms become capable of fertilizing an egg. They identified these sperms by measuring how much calcium they absorbed. By using this method in live animals, they were able to identify a specific gene, Rd3, as being crucial for maintaining sperm cell health, particularly during sperm cell development. Despite Rd3’s previous association with eye function, the team found it is also highly active in round sperm cells, an early stage in sperm production, and that it plays a significant role in regulating sperm health. This discovery was made possible by examining how Rd3 interacts with mitochondria, structures responsible for energy production within cells.
To further understand Rd3’s function, Suzuki and his colleagues developed Hub-Explorer, a computational tool that revealed Rd3’s impact on regulation of oxidative stress — a condition linked to cellular damage. Rd3’s role in regulating oxidative stress revealed its significance in maintaining sperm integrity during development.
“While women have many available birth control options, choices for men remain limited,” says Noguchi, a first author of this paper. “This new screening method holds promise by aiding the discovery of key molecules, potentially leading to new birth control options and infertility therapies for men.”
“These discoveries not only advance our understanding of sperm cell development but also demonstrate the potential to uncover mysteries in different biological processes,” adds Suzuki. “The method can also be applied to other tissues, potentially expediting the development of drugs for a wide range of diseases.”
Despite these advancements, challenges remain. The researchers observed a gradual decline in the number of cells with targeted genes, suggesting room for improvement. They are currently exploring alternative approaches to enhance the effectiveness of their technique, and they plan to apply it to investigate various biological processes and diseases in other areas of the body.

Researchers who work with tiny drug carriers known as lipid nanoparticles have developed a new type of material capable of reaching the lungs and the eyes, an important step toward genetic therapy for hereditary conditions like cystic fibrosis and inherited vision loss.
Findings of the study led by Gaurav Sahay and Yulia Eygeris of the Oregon State University College of Pharmacy and Renee Ryals of Oregon Health & Science University were published today in the Proceedings of the National Academy of Sciences.
Unlike other types of lipid nanoparticles that tend to accumulate in the liver, the ones in this study, based on the compound thiophene, are able to navigate their way to the tissues of the lungs and retina, where they deliver their therapeutic payload. The researchers refer to these new lipids as Thio-lipids.
The collaboration demonstrated, by using animal models, the possibility of using Thio-lipids in lipid nanoparticles to deliver messenger RNA, the technology underpinning COVID-19 vaccines, to combat genetic blindness and pulmonary disease.
“These nanoparticles filled with fatty lipids can encapsulate genetic medicines like mRNA and CRISPR-Cas9 gene editors, which can be used to treat and even cure rare genetic diseases,” said Eygeris, a senior research associate at OSU. “Chemical structures of the lipids determine how potent are the lipid nanoparticles and which organ they can reach from the bloodstream.”
Lipids are organic compounds containing fatty tails and are found in many natural oils and waxes, and nanoparticles are tiny pieces of material ranging in size from one- to 100-billionths of a meter. Messenger RNA delivers instructions to cells for making a particular protein.
With the coronavirus vaccines, the mRNA carried by the lipid nanoparticles instructs cells to make a harmless piece of the virus’ spike protein, which triggers an immune response from the body.

As a therapy for vision impairment resulting from inherited retinal degeneration, the mRNA would instruct cells in the retina — which don’t work right because of a genetic mutation — to manufacture the proteins needed for sight. Inherited retinal degeneration, commonly abbreviated to IRD, encompasses a group of disorders of varying severity and prevalence that affect one out of every few thousand people worldwide.
An example of a genetic pulmonary condition is cystic fibrosis, a progressive disorder that results in persistent lung infection and affects 30,000 people in the U.S., with about 1,000 new cases identified every year.
One faulty gene — the cystic fibrosis transmembrane conductance regulator, or CFTR — causes the disease, which is characterized by lung dehydration and mucus buildup that blocks the airway.
The thiophene-based lipid nanoparticle study, which involved mice and non-human primates, stems from a $3.2 million grant to Sahay and Ryals from the National Eye Institute. The grant’s purpose is addressing limitations associated with the current primary means of delivery for gene editing: a type of virus known as adeno-associated virus, or AAV.
“AAV has limited packaging capacity compared to lipid nanoparticles and it can prompt an immune system response,” said Sahay, a professor of pharmaceutical sciences. “It also doesn’t do fantastically well in continuing to express the enzymes the editing tool uses as molecular scissors to make cuts in the DNA to be edited.”
Sahay calls the Thio-lipid findings “highly encouraging” but says more studies are needed, including research on the lipids’ long-term impact on retinal health.
“But we think our results serve as a proof of concept and we will continue to explore Thio-lipids in potential treatments of pulmonary and retinal genetic diseases,” he said.
In addition to the National Eye Institute, funding and research support were provided by the Oregon National Primate Research Center and the Casey Eye Institute.

Space weather experts at the University of Surrey are urging regulators and space tourism innovators to work together to protect their passengers and crews from the risks of space weather radiation exposure.
The Earth’s atmosphere and magnetic field protect people on the ground from exposure to unpredictable surges of electrically charged particles coming from the sun. However, there can be dramatic increases in potential radiation exposure at higher altitudes, such as those envisaged for space tourist flights.
Space weather cannot yet be predicted and can lead to health risks such as damage to DNA, and it could lead to cancer. Despite this, space tourists currently receive little information and few warnings.
Chris Rees, lead author of a new paper on radiation risks to space tourism and a postgraduate researcher at Surrey Space Centre, said:
“Although space tourism is very niche, it will quickly grow as an industry. With increased flights, more people could be impacted by cosmic radiation exposure, especially during rapid changes in space weather. We’re recommending how regulators and industry should work together to keep people safe without unnecessarily holding back innovation.”
JR Catchpole, co-author of the paper and a space law expert at Foot Anstey LLP, said:
“International action is needed by regulators, but meanwhile, the early movers in the sector, like Virgin Galactic and Blue Origin, need to watch themselves and their passengers. The principles of informed consent mean stronger warnings and clearer information may be required.”
The paper, which is published in Space Policy, makes a series of recommendations:

Regulatory bodies should work closely with industry to ensure regulations are practical, effective and reflect technological advances International standards are needed to ensure consistent regulations Safety is crucial, which means clear information for space tourists and more monitoring of cosmic radiation during short space flights Regulation must encourage innovation within this young industry, not stifle it

Adults who reported drinking two liters (about 67 ounces) or more of sugar- or artificially sweetened drinks per week had a higher risk of an irregular heart rhythm known as atrial fibrillation compared with adults who drank fewer such beverages, according to new research published today in Circulation: Arrhythmia and Electrophysiology, a peer-reviewed journal of the American Heart Association.
The study also found that drinking one liter (about 34 ounces) or less per week of pure, unsweetened juice, such as orange or vegetable juice, was associated with a lower risk of atrial fibrillation (AFib). However, the study could not confirm whether the sweetened drinks caused AFib, yet the association remained after accounting for a person’s genetic susceptibility to the condition.
Consuming sweetened drinks has been linked to Type 2 diabetes and obesity in previous research. This large study of health data in the UK Biobank is among the first to assess a possible link between sugar- or artificially sweetened beverages and AFib. Atrial fibrillation is a condition in which the heart beats irregularly, increasing the risk of stroke by five-fold. More than 12 million people are expected to have AFib by 2030, according to the American Heart Association’s 2024 Heart Disease and Stroke Statistics.
“Our study’s findings cannot definitively conclude that one beverage poses more health risk than another due to the complexity of our diets and because some people may drink more than one type of beverage,” said lead study author Ningjian Wang, M.D., Ph.D., a researcher at the Shanghai Ninth People’s Hospital and Shanghai Jiao Tong University School of Medicine in Shanghai, China. “However, based on these findings, we recommend that people reduce or even avoid artificially sweetened and sugar-sweetened beverages whenever possible. Do not take it for granted that drinking low-sugar and low-calorie artificially sweetened beverages is healthy, it may pose potential health risks.”
Researchers reviewed data from dietary questionnaires and genetic data for more than 200,000 adults free of AFib at the time they enrolled in the UK Biobank, between 2006 and 2010. During the nearly 10-year follow-up period, there were 9,362 cases of AFib among the study participants.
The analysis found: Compared to people who did not consume any sweetened drinks, there was a 20% increased risk of atrial fibrillation among people who said they drank more than 2 liters per week (about 67 ounces or more, or roughly one 12-ounce drink 6 days a week) of artificially sweetened beverages; and a 10% increased risk among participants who reported drinking 2 liters per week or more of sugar-sweetened beverages. People who said they drank 1 liter (about 34 ounces) or less of pure fruit juice each week had an 8% lower risk of atrial fibrillation. Participants who consumed more artificially sweetened beverages were more likely to be female, younger, have a higher body mass index and a higher prevalence of Type 2 diabetes. Participants who consumed more sugar-sweetened beverages were more likely to be male, younger, have a higher body mass index, a higher prevalence of heart disease and lower socioeconomic status. Those who drank sugar-sweetened beverages and pure juice were more likely to have a higher intake of total sugar than those who drank artificially sweetened drinks. Smoking may have also affected risk, with smokers who drank more than two liters per week of sugar-sweetened beverages having a 31% higher risk of AFib, whereas no significant increase risk was noted for former smokers or people who never smoked.”These novel findings on the relationships among atrial fibrillation risk and sugar- and artificially sweetened beverages and pure juice may prompt the development of new prevention strategies by considering decreasing sweetened drinks to help improve heart health,” Wang said.

Researchers also evaluated whether a genetic susceptibility to AFib was a factor in the association with sweetened beverages. The analysis found the AFib risk was high with the consumption of more than 2 liters of artificially sweetened drinks per week regardless of genetic susceptibility.
“Although the mechanisms linking sweetened beverages and atrial fibrillation risk are still unclear, there are several possible explanations, including insulin resistance and the body’s response to different sweeteners,” Wang said. “Artificial sweeteners in food and beverages mainly include sucralose, aspartame, saccharin and acesulfame.”
A 2018 science advisory from the American Heart Association noted that there is a scarcity of large, long-term, randomized trials on the efficacy and safety of artificial sweeteners. The writing group advised against prolonged consumption of low-calorie sweetened beverages by children; however, they noted artificially sweetened drinks may be a useful replacement strategy to reduce consumption of sugar-sweetened beverages among adults who habitually drink a high number of sugar-sweetened drinks.
American Heart Association nutrition committee member Penny M. Kris-Etherton, Ph.D., R.D., FAHA, said these findings on artificially sweetened beverages are surprising “given that two liters of artificially sweetened beverages a week is equivalent to about one 12-ounce diet soda a day.”
Kris-Etherton, an emeritus professor of nutritional sciences at Penn State University, was a co-author of the association’s science advisory on artificial sweeteners.
“This is the first study to report an association between no- and low-calorie sweeteners and also sugar-sweetened beverages and increased risk of atrial fibrillation,” she said. “While there is robust evidence about the adverse effects of sugar-sweetened beverages and cardiovascular disease risk, there is less evidence about adverse health consequences of artificial sweeteners.

“We still need more research on these beverages to confirm these findings and to fully understand all the health consequences on heart disease and other health conditions. In the meantime, water is the best choice, and, based on this study, no- and low-calorie sweetened beverages should be limited or avoided.”
The American Heart Association’s 2016 dietary guidelines align with the U.S.D.A.’s 2020-2025 Dietary Guidelines for Americans in suggesting sugar-sweetened beverage consumption be minimized; they also note there is unclear evidence of the role of no- and low-calorie sweeteners on many health outcomes. The American Heart Association recommends limited intake of sugar-sweetened beverages, such as such as soft drinks, fruit drinks, sports drinks, energy drinks, sweetened teas and coffee drinks. Healthy beverage options noted are water and fat-free or low-fat milk, while unsweetened fresh, frozen or packaged fruit juice is recommended instead of fruit juice with added sugar. A half cup of pure juice (such as orange juice or grapefruit juice) is recognized as one fruit serving.
Study background and details: The UK Biobank is a large, biomedical database with health records for about 500,000 adults — enrolled from 2006 until 2010 — who lived in the U.K. and received health care through the U.K.’s National Health Service. Data was reviewed for 201,856 participants of the U.K. Biobank, ranging in age from 37 to 73 years old, and 45% were male. Participants were followed for an average of nearly 10 years. Blood samples were collected to measure genetic risk for AFib, and participants answered more than one 24-hour questionnaire about their diet on five repeated occasions between April 2009 and June 2012.The limitations of this study include that the findings were observational and cannot prove causation between consumption of certain types of beverages and AFib risk. In addition, the findings relied on participants to recall their own diets, so there may have been memory errors or bias. It is also unknown if the sugar- and artificially sweetened drinks contained caffeine.

When the pandemic started, people who felt unwell had to join long queues for lab-based PCR tests and then wait for two days to learn if they had the COVID-19 virus or not.
In addition to significant inconvenience, a major drawback was the substantial and expensive logistics needed for such laboratory tests, while testing delays increased the risk of disease spread.
Now a team of biomedical engineers at UNSW Sydney have developed a new technology offering test strips which are just as accurate as the lab-based PCR tests but offer rapid, on-the-spot disease detection. And according to research published today in Nature Communications, it’s not just public health that the technology may benefit.
Senior researcher Professor Ewa Goldys, with UNSW’s Graduate School of Biomedical Engineering, says the new technology is like having “PCR in your pocket,” and that it opens up possibilities for biomedical and environmental diagnostics in the food industry, agriculture, and biosafety management.
“Not only can we easily detect specific gene sequences in a sample, but, unlike PCR, we can do it at room temperature using a test strip that looks exactly like a well-known RAT Covid test — you already know what to do with it,” she says.
“So, no more queuing for that PCR test in the future. Also, the cost is very low — currently less than a few dollars per test.”
Study author Dr Fei Deng adds that the new test strips could expedite rapid response to emerging pathogens such as mosquito borne or lumpy skin diseases, reveal hotspots of antibiotic resistance or help look for threatened animal species.

“This could transform human and animal infection control as well as quarantine and bio-diversity conservation efforts,” he says.
“We think we created a new benchmark in biosensing — our gene-based tests will be able to be performed anywhere, anytime, by virtually anyone.”
How it works
Co-author Dr Yi Li says that to bring the new test strips up to PCR standards the team first made tiny DNA nano-circles containing a short sequence of the target DNA, such as the COVID virus. Each nano-circle is only about 2 nanometres in size, way too small to be seen by any microscope.
These DNA nano-circles and the tested sample were mixed with CRISPR/Cas proteins.
These proteins — renowned by their association with the Nobel Prize winning CRISPR/Cas gene editing technology — were programmed by the UNSW team to cut DNA of the nano-circles — but only when activated by DNA from the targeted pathogen.

“The interaction of a suitably programmed CRISPR/Cas protein with the gene target we are trying to detect causes the DNA nano-circles to break up, linearise and become ‘fake targets’,” Dr Li says.
This novel approach produces a molecular chain reaction.
“We unleash a huge cascade of fake targets which is easy to detect with the testing strips, even if only a few molecules of the original gene target are present. ”
The method was illustrated in samples of the COVID-19 virus and helicobacter bacteria that cause stomach ulcers.
Watching with interest
Prof. Goldys says the response from industry to the team’s innovation has been overwhelmingly positive.
“The industrial and clinical rollout of our technology to the Australian industry has already begun, with the intention to keep the manufacturing onshore. We will be building on the emerging industrial infrastructure for the RNA vaccine production.”
She says some of the applications the new biosensing method could be in biosecurity, where testing strips could detect potential invasive marine species; environmental science where DNA testing of the environmental samples could indicate the presence or absence of a particular threatened species; and an intriguing use of the biosensing strips to detect cancer cells.
“In our published study we were also able to detect cancer mutations in patients’ samples in a clinical setting,” Prof. Goldys says.
“We hope this will open a path towards universal monitoring of patients undergoing cancer therapies.”
The research is detailed in the journal Nature Communications and was carried out by researchers affiliated with UNSW and the Garvan Medical Research Institute.

How to optimise running? A new mathematical model1 has shown, with great precision, the impact that physiological and psychological parameters have on running performance and provides tips for optimised training. The model grew out of research conducted by a French-British team including two CNRS researchers2, the results of which will appear on March 5th 2024 in the journal Frontiers in Sports and Active Living.
This innovative model was developed thanks to extremely precise data3 from the performances of Matthew Hudson-Smith (400m), Femke Bol (400m), and Jakob Ingebrigtsen (1500m) at the 2022 European Athletics Championships in Munich, and for Gaia Sabbatini (1500m) at the 2021 European Athletics U23 Championships in Tallinn. It led to an optimal control problem for finishing time, effort, and energy expenditure. This is the first time that such a model has also considered the variability of motor control, i.e., the role of the brain in the process of producing movement. The simulations allow the researchers to have access to the physiological parameters of the runners — especially oxygen consumption (or VO2)4, and energy expenditure during the race — as well as compute their variations. Quantifying costs and benefits in the model provides immediate access to the best strategy for achieving the runner’s optimal performance.
The study details multiple criteria, such as the importance of a quick start in the first 50 metres (due to the need for fast oxygen kinetics), or reducing the decrease in velocity in a 400m race. The scientists also demonstrated that improving the aerobic metabolism (oxygen uptake) and the ability to maintain VO2 are crucial elements to 1500m race performance.
The development of this model represents considerable progress in studying variations in physiological parameters during championship races, for which in vivo measurements are not possible.
Notes:
1 For more details on the model, “Be a champion, 40 facts you didn’t know about sports and science,” Amandine Aftalion, Springer, to appear May 14th 2024.
2 From the Centre for Analysis and Social Mathematics (CNRS/EHESS), in collaboration with the Jacques-Louis Lions Laboratory (CNRS/Sorbonne Université/Université Paris Cité) and the Carnegie School of Sport at Leeds Beckett University.
3 Values measured every 100 milliseconds.
4 Rate at which oxygen is transformed into energy.

An inexpensive measure of obesity in children and adolescents that could replace body mass index (BMI) has been identified in a new study as waist circumference-to-height ratio. This measure detected excess fat mass and distinguished fat mass from muscle mass in children and adolescents more accurately than BMI. The study was conducted in collaboration between the University of Bristol in the UK, the University of Exeter in the UK, and the University of Eastern Finland, and the results were published in Pediatric Research.
The prevalence of childhood and adolescent obesity has reached an epidemic proportion and is affecting nearly 1 in 4 children in the current decade. Unfortunately, obesity in the young population has been associated with cardiovascular, metabolic, neurological, musculoskeletal diseases and premature death in adulthood. Accurately detecting overweight and obesity in children is critical to initiating timely interventions. For nearly a generation, weight-to-height ratio charts and BMI for age and sex have been used to diagnose children with obesity. However, these surrogate assessment tools are inaccurate in childhood and adolescence since they do not distinguish fat mass from muscle mass.For instance, two children with similar BMI might have different proportions of fat and muscle mass which makes obesity diagnosis difficult.
Expensive tools such as the dual-energy Xray absorptiometry (DEXA) scan accurately measures fat and muscle content of the body, but this device is not readily available in primary health care centres. Recently, the American Academy of Pediatrics (AAP) published a clinical guideline on childhood obesity and requested urgent research on inexpensive and accurate alternative measures of obesity.
Emerging studies in adults appear to suggest that waist circumference-to-height ratio predicts premature death better than BMI and could be a potential added tool to BMI measure in improving the diagnosis of obesity.
However, there has been no former evaluation of how much waist circumference-to-height ratio measurements agree with DEXA-measured fat mass and muscle mass during growth from childhood to young adulthood. In addition, the threshold of waist circumference-to-height ratio needed to detect excess fat in children is not clear, hence this study.
The current study is the largest and the longest follow-up DEXA-measured fat mass and muscle mass study in the world using the University of Bristol’s Children of the 90s data (also known as the Avon Longitudinal Study of Parents and Children). The study included 7,237 children (51% females) aged 9 years who were followed-up until age 24 years. Their BMI and waist circumference-to-height ratio were measured at ages 9, 11, 15, 17, and 24 years. When different devices measure a variable with an exact resemblance, it is described as perfect agreement of the devices with a score of 100%. For example, two DEXA scans from different manufacturers would measure fat mass with a near-perfect agreement of 99 to 100%.
Waist circumference-to-height ratio had a very high agreement of 81 — 89% with DEXA-measured total body fat mass and trunk fat mass, but a low agreement with muscle mass (24 — 39%). BMI had a moderate agreement with total fat mass and trunk fat mass (65 — 72%) and muscle mass (52 — 58%). Since BMI had a moderate agreement with DEXA-measured muscle mass, it is difficult to specify whether BMI measures excess fat or muscle mass. The optimal waist circumference-to-height ratio cut points that predicted the 95th percentile of total fat mass in males was 0.53 and 0.54 in females. This cut point detected 8 out of 10 males and 7 out of 10 females who truly had excess DEXA-measured fat. The cut point also identified 93 out of 100 males and 95 out of 100 females who truly do not have excess fat.
“This study provides novel information that would be useful in updating future childhood obesity guidelines and policy statements. The average waist circumference-to-height ratio in childhood, adolescence, and young adulthood is 0.45, it does not vary with age and among individuals like BMI. Waist circumference-to-height ratio might be preferable to BMI assessment in children and adolescent clinics as an inexpensive tool for detecting excess fat. Parents should not be discouraged by the BMI or weight of their children but can inexpensively confirm whether the weight is due to increase in excess fat by examining their kid’s waist circumference-to-height ratio,” says Andrew Agbaje, an award-winning physician and pediatric clinical epidemiologist at the University of Eastern Finland.
Dr Agbaje’s research group (urFIT-child) is supported by research grants from Jenny and Antti Wihuri Foundation, the Finnish Cultural Foundation Central Fund, the Finnish Cultural Foundation North Savo Regional Fund, the Orion Research Foundation, the Aarne Koskelo Foundation, the Antti and Tyyne Soininen Foundation, the Paulo Foundation, the Yrjö Jahnsson Foundation, the Paavo Nurmi Foundation, the Finnish Foundation for Cardiovascular Research, Ida Montin Foundation, Eino Räsänen Fund, Matti and Vappu Maukonen Fund, Foundation for Pediatric Research, and Alfred Kordelin Foundation.

Bacteria can be tricked into sending death signals to stop the growth of their slimy, protective homes that lead to deadly infections, a new study demonstrates.
The discovery by Washington State University researchers could someday be harnessed as an alternative to antibiotics for treating difficult infections. Reporting in the journal, Biofilm, the researchers used the messengers, which they named death extracellular vesicles (D-EVs), to reduce growth of the bacterial communities by up to 99.99% in laboratory experiments.
“Adding the death extracellular vesicles to the bacterial environment, we are kind of cheating the bacteria cells,” said Mawra Gamal Saad, first author on the paper and a graduate student in WSU’s Gene and Linda Voiland School of Chemical Engineering and Bioengineering. “The cells don’t know which type of EVs they are, but they take them up because they are used to taking them from their environment, and with that, the physiological signals inside the cells change from growth to death.”
Bacterial resistance is a growing problem around the world. In the U.S., at least 2 million infections and 23,000 deaths are attributable to antibiotic-resistant bacteria each year, according to the U.S. Centers for Disease Control. When doctors use antibiotics to treat a bacterial infection, some of the bacteria can hide within their tough-to-penetrate, slimy home called a biofilm. These subpopulations of resistor cells can survive treatment and are able to grow and multiply, resulting in chronic infections.
“They are resistant because they have a very advanced and well-organized adaptive system,” said Saad. “Once there is a change in the environment, they can adapt their intracellular pathways very quickly and change it to resist the antibiotics.”
In their new study, the researchers discovered that the extracellular vesicles are key to managing the growth of the protective biofilm. The vesicles, tiny bubbles from 30 to 50 nanometers or about 2,000 times smaller than a strand of hair, shuttle molecules from cells, entering and then re-programming neighboring cells and acting as a cell-to-cell communications system.
As part of this study, the researchers extracted the vesicles from one type of bacteria that causes pneumonia and other serious infections. They determined that the bacteria initially secrete vesicles, called growth EVs, with instructions to grow its biofilm, and then later, depending on available nutrients, oxygen availability and other factors, send EVs with new instructions to stop growing the biofilm.

The researchers were able to harness the vesicles with the instructions to stop growth and use them to fool the bacteria to kill off the biofilm at all stages of its growth. Even when the biofilms were healthy and rapidly growing, they followed the new instructions from the death EVs and died. The death EVs can easily penetrate the biofilm because they are natural products secreted by the bacteria, and they have the same cell wall structure, so the cells don’t recognize them as a foreign enemy.
“By cheating the bacteria with these death EVs, we can control their behavior without giving them the chance to develop resistance,” said Saad. “The behavior of the biofilm just changed from growth to death.”
WSU Professor and corresponding author Wen-Ji Dong, who has been studying the vesicles for several years initially thought that all of the bacterial-secreted vesicles would promote cell growth. The researchers were surprised when they found that older biofilms provided instructions on shutting themselves down.
“So now we’re paying attention to the extracellular vesicles secreted by older biofilms because they have therapeutic potential,” he said.
The researchers are applying for research funding from the National Institutes of Health to continue investigating exactly how the messengers work and how well the process works with other bacterial types or fungi. They are working with WSU’s Office of Commercialization and have applied for a provisional patent.

Although several studies have linked smoking during pregnancy with neurodevelopmental disorders, the results of behavioral experiments in mice prenatally exposed to nicotine have been inconsistent. In a recent study, scientists from Japan developed a deep learning-based framework to automatically observe and classify mice behavior in such experiments, producing more accurate and unbiased results. They show that prenatal exposure to nicotine could increase the risk of autism spectrum- and attention deficit/hyperactivity disorders in newborns.
The fact that smoking is a risk factor for several diseases, including cancer, stroke, and diabetes, has been known for approximately half a century. However, over the past few decades, scientists have brought to light many of the detrimental effects of smoking during pregnancy, linking this habit to high infant mortality, failed delivery, and low body weight at birth. In addition, recent studies suggest that prenatal nicotine exposure (PNE) may be related to neurodevelopmental disorders, such as attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).
For a long time now, scientists have used animal models (like rodents) to understand how PNE leads to neurodevelopmental disorders. By carefully analyzing the behavior of rodents, they can infer whether PNE is causing neurological changes and the brain regions affected by it; this can later be confirmed through histological analyses.
Unfortunately, thus far, studies on behavioral changes induced by PNE in mice have shown varied results, some of which are contradictory. Although there could be multiple reasons behind these discrepancies, human error and bias are prime suspects. In general, the assessment of complex animal behaviors, especially social interactions, relies on the efforts of human observers, which introduces a baseline level of subjectivity that is hard to dispel. But what if we can leverage artificial intelligence (AI) to produce more accurate and unbiased results from observations of PNE mice behavior?
In a recent study published in Cells on 1 February 2024, researchers from the Department of Molecular and Cellular Physiology at the Shinshu University School of Medicine, including graduate student Mengyun Zhou, Assistant Professor Takuma Mori, and Professor Katsuhiko Tabuchi, developed and trained a deep learning-based system to automatically analyze footage from behavioral experiments on mice. They used this tool to explore the behavioral changes induced by PNE in mice without observer biases, seeking to shed light on the link between nicotine and neurodevelopmental disorders.
The proposed AI-based framework relied on a combination of two well-established open-source toolkits, namely DeepLabCut and Simple Behavioral Analysis (SimBA). “AI tools can label the body parts of animals in a markerless video footage and precisely estimate their poses using supervised machine learning,” explains Prof. Tabuchi. “Since animal behaviors are defined as a specific arrangement of body parts over a short period of time, deep-learning toolkits like SimBA can use the pose estimations obtained with DeepLabCut to classify different types of animal behaviors.”
After reaching an optimal training protocol for their framework using manually labeled data, the researchers conducted several experiments using PNE and control mice, looking for indicators of ADHD- and ASD-like behaviors. First, they carried out cliff avoidance reaction tests, which are used to test impulsivity. In these tests, they placed the subject mouse on top of a slightly elevated platform and took note — both manually and with the AI system — of how long the mouse waited before jumping down the platform. The test results suggested that PNE mice are more impulsive, a behavioral feature of ADHD in humans.

They also tested the working memory of mice using a Y-shaped maze and counted the number of times each mouse spontaneously switched from one arm of the maze to another. “We observed a decrease in the spontaneous alteration in PNE mice, suggesting that their working memory was altered, which is another behavioral feature of ADHD,” comments Mengyun Zhou. “These results suggest prenatal exposure to nicotine may cause ADHD in mice, which is consistent with clinical reports in humans.”
Finally, the researchers conducted open-field and social-interaction experiments, which represented the main challenge for their AI-based system. In these experiments, the researchers observed either one or two mice behaving freely in a large enclosure and looked for indicators of anxiety and social behaviors, such as grooming and following. Interestingly, PNE mice exhibited social behavioral deficits and increased anxiety which are features of ASD. Subsequent histological analysis of hippocampal brain tissue confirmed decreased neurogenesis, a hallmark of ASD. Thus, it appears that smoking may not only increase the risk of ADHD, but also ASD.
Worth noting, the results obtained using the AI-based system were highly reliable, as Prof. Tabuchi highlights: “We validated the accuracy of our behavioral analysis framework by drawing a careful comparison between the results generated by the model and behavior assessments made by multiple human annotators, which is considered the gold standard.” These analyses cement the potential of the proposed approach and showcase its capabilities for many types of behavioral studies.
With any luck, further efforts will pave the way to a solid understanding of mechanisms behind neurodevelopmental disorders like ASD and ADHD, ultimately leading to better diagnostic tools and therapeutic methods.