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With the rise in gestational diabetes and metabolic disorders during pregnancy, metformin is also being prescribed more frequently. Although it is known that the oral antidiabetic agent can cross the placental barrier, the impacts on the brain development of the child are largely unknown. An interdisciplinary research team from the German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE) have now been able to demonstrate in a mouse model that although metformin has positive effects in pregnant animals, it does not in the offspring. The results were published in the specialist journal Molecular Metabolism.
Current figures show that around one in six pregnant women worldwide are affected by a special form of diabetes known as gestational diabetes. According to the Robert Koch Institute, 63,000 women in Germany were affected by the disease in 2021, and the trend is increasing. These numbers are alarming because excessively high blood sugar levels during pregnancy are associated with negative consequences for mother and child. This increases the risk of affected women developing type 2 diabetes later on and their children have a higher risk of developing metabolic disorders and being overweight.
Long-Term Effect of Metformin on Offspring is Unclear
For several years, the placenta-crossing oral antidiabetic agent metformin has been increasingly gaining importance as an alternative to insulin administration when lifestyle changes show no success during the treatment of gestational diabetes. However, there are currently only a few studies on the long-term effects of metformin on the health of offspring. It is known that metformin has an impact on the AMPK signaling pathway, which regulates the networking of nerve cells during brain development.
The interdisciplinary team of DIfE researchers led by Junior Research Group Leader Dr. Rachel Lippert therefore grappled with two central questions: Is metformin treatment only beneficial for the mother or also the child? And does metformin treatment lead to long-term negative physiological changes in the offspring, especially in connection with the development of neuronal circuits in the hypothalamus, a critical region in the regulation of energy homeostasis?
Mouse Models Shed some Light
To answer the key questions, the researchers used two mouse models to represent the main causes of gestational diabetes:
severe obesity of the mother before pregnancy and excessive weight gain during pregnancy. These metabolic states were achieved by means of different feeding patterns, with the mice receiving either a high-fat or control diet. The antidiabetic treatment of female mice and their offspring took place during the lactation period as this corresponds to the third trimester of a human pregnancy in terms of brain development.

Treatment involved insulin, metformin, or a placebo, whereby the dosage was based on standard human treatments. The research team collected data on the body weight of the mice, analyzed various metabolic parameters and hormones, and examined molecular signaling pathways in the hypothalamus.
Maternal Metabolic State is Crucial
“As a result of antidiabetic treatment in the early postnatal period, we were able to identify alterations in the weight gain and hormonal status of the offspring, which were critically dependent on the metabolic state of the mother,” explains Lippert. Furthermore, sex-specific changes in hypothalamic AMPK signaling in response to metformin exposure were also observed. Together with the metformin-induced shift in the examined hormone levels, the results indicate that the maternal metabolic state must be taken into account before starting the treatment of gestational diabetes.
Focusing on Prevention
According to Rachel Lippert, treatment of gestational diabetes in future could entail developing a medication that is available for all and does not cross the placenta. “Given the increasing prevalence, education about gestational diabetes and preventive measures are of vital importance. If we can find a way to manage lifestyle and diet more proactively, we are in a better position to exploit the potential of gestational diabetes treatment,” says Lippert.

A study of more than 3,000 middle-aged and older women living in England showed that those who believed they had encountered gender discrimination were more likely to report declines in wellbeing over time. Ruth Hackett of King’s College London, UK, and colleagues present these findings in the open-access journal PLOS ONE on March 20, 2024.
Prior research suggests that people who perceive that they have experienced gender discrimination are more likely to report poorer mental wellbeing. However, most studies have not examined wellbeing over time, or have focused on younger women.
To better understand this relationship among older women, Hackett and colleagues analyzed data from 3,081 women enrolled in the English Longitudinal Study of Ageing (ELSA), which follows a large group of people over 50 years of age.
In 2010 or 2011, each woman answered questions about how often they encountered different discriminatory situations — such as being harassed or being treated with less respect or courtesy — and whether they attributed that discrimination to their gender or another characteristic, such as race or age. At two points in time, each woman also answered standard questionnaires for evaluating mental wellbeing; once in 2010 or 2011 and again in 2016 or 2017.
9.2 percent of the women reported perceived gender discrimination, most commonly situations where they were treated with less respect or courtesy. Overall, those who perceived gender discrimination also reported more depressive symptoms, more loneliness, and lower quality of life and life satisfaction. Between the two time points, they were more likely to report declines in quality of life and life satisfaction, as well as increased loneliness. These results held true after statistically accounting for other wellbeing-related factors, such as age, wealth, and physical activity.
The findings suggest that perceived gender discrimination may be linked to declines in mental wellbeing for middle-aged and older women, prompting the researchers to call for more efforts to address gender discrimination. They also note the need for further research to clarify the mechanisms driving this link and to address the limitations of their study, such as its lack of non-white participants.
The authors add: “We found that middle-aged and older women who perceived sexism were more likely to be depressed and lonely than women who did not perceive sexism. These women also reported low levels of life satisfaction and poor quality of life. The study findings are particularly concerning as they indicate an enduring impact of gender-based discrimination on mental health and wellbeing six years later.”

Frequent musculoskeletal pain is linked with an increased risk of exiting work and retiring earlier, according to a new study from the University of Portsmouth.
The paper published this week in open-access journal PLOS ONE found the association between musculoskeletal pain and retiring earlier persisted even after accounting for working conditions, job satisfaction and sex.
Dr Nils Niederstrasser and colleagues used data on 1,156 individuals aged 50+ living in England who took part in the English Longitudinal Study of Ageing. Over the course of the 14-year data collection period, 1,073 of the individuals retired.
The researchers found that people with musculoskeletal pain complaints tended to retire earlier compared to pain-free participants. Participants suffering from musculoskeletal pain were also 1.25 times more likely to cease work sooner, whether or not they described themselves as retired.
Previous studies have shown higher rates of absenteeism, reduced working capacity and reduced income for people with chronic musculoskeletal pain, but few studies have specifically focused on the effects of chronic pain on the employment status of older populations.
Dr Niederstrasser, from the University’s Department of Psychology, said: “The older you get, the more prevalent pain becomes. This paper really highlights the scope of the problem, which found that pain — above and beyond all other variables — is predicting whether or not someone retires earlier.”
Other factors associated with earlier retirement age included higher work dissatisfaction and higher self-perceived social status. Frequent musculoskeletal pain remained a significant predictor of earlier retirement and risk of finishing work at earlier ages even when taking into account the influence of job satisfaction, depressive symptoms, self-perceived social status, sex, and working conditions.
The authors conclude that pain experiences can lead to poor work outcomes and point out that further research should establish the mechanisms and decision making involved in leaving the workforce for people with frequent musculoskeletal pain.
Dr Niederstrasser added: “It is remarkable that pain predicts earlier retirement and work cessation to a similar extent or even more strongly than other variables, such as job satisfaction or specific job demands. It shows just how much impact pain can have on all aspects of people’s lives.
“For people to remain in the workforce in good health, pain needs to be addressed much earlier on. If people retire earlier because they can’t work anymore, but they don’t necessarily have the pension built up or the income to support themselves, we’re heading towards a crisis. We already have problems with older people living in poverty, and this is only going to get worse.”

Measuring between 3 to 3.5 meters, 16 million years old: Paleontologists from the University of Zurich have announced the discovery of a new species of freshwater dolphin in the Peruvian Amazon region. Surprisingly, its closest living relatives can be found in the river dolphins of South Asia.
River dolphins are among the rarest modern cetaceans, with most extant species critically endangered. Despite their similar appearance, however, these animals are not directly related, but represent the late survivors of different cetacean groups that once inhabited our planet.
An international research team led by the University of Zurich (UZH) has now revealed the largest river dolphin ever found, measuring between 3 and 3.5 meters. The new species, named Pebanista yacuruna after a mythical aquatic people believed to inhabit the Amazon basin, was found in Peruvian Amazonia and is dated to be 16 million years old.
Changing landscape drove giant dolphin to extinction
The new dolphin species belongs to the Platanistoidea, a group of dolphins that were common in the world’s oceans between 24 and 16 million years ago. The researchers believe that their originally marine ancestors invaded the prey-rich freshwater ecosystems of proto-Amazonia and adapted to this new environment.
“Sixteen million years ago, the Peruvian Amazonia looked very different from what it is today,” says lead author Aldo Benites-Palomino from the Department of Paleontology at UZH. “Much of the Amazonian plain was covered by a large system of lakes and swamps called Pebas.” This landscape included aquatic, semi-aquatic and terrestrial ecosystems (swamps, floodplains, etc.) and stretched across what is today Colombia, Ecuador, Bolivia, Peru and Brazil.
When the Pebas system began to give way to modern Amazonia about 10 million years ago, new habitats caused Pebanista’s prey to disappear, driving the giant dolphin to extinction. This opened an ecological niche that was exploited by relatives of today’s Amazon river dolphins (Inia), which were also facing extinction in the oceans due to the rise of new cetaceans, such as modern oceanic dolphins.

Findings shed light on the evolutionary history of freshwater dolphins
“We discovered that its size is not the only remarkable aspect,” says Aldo Benites-Palomino. “With this fossil record unearthed in the Amazon, we expected to find close relatives of the living Amazon River dolphin — but instead the closest cousins of Pebanista are the South Asian river dolphins (genus Platanista).”
Pebanista and Platanista both share highly developed facial crests, which are specialized bony structures associated with echolocation — the ability to “see” by emitting high-frequency sounds and listening or their echoes, which they rely on heavily for hunting.
“For river dolphins, echolocation, or biosonar, is even more critical as the waters they inhabit are extremely muddy, which impedes their vision,” explains Gabriel Aguirre-Fernández, a UZH researcher who also participated in this study. The elongated snout with many teeth suggests that Pebanista fed on fish, as other species of river dolphins do today.
“After two decades of work in South America we had found several giant forms from the region, but this is the first dolphin of its kind,” adds Marcelo R. Sánchez-Villagra, director of the Department of Paleontology at UZH. “We were especially intrigued by its peculiar biogeographical deep-time history.”
Finding Fossils in the Amazon
The Amazon rainforest is one of the harshest regions for paleontological fieldwork. Fossils are only accessible during the dry season, when river levels are low enough to expose the ancient fossil-bearing rocks. If these fossils are not collected in time, the rising water levels during the rainy season will sweep them away and they will be lost forever.
The holotype — a single physical specimen on which the description and name of a new species is based — of Pebanista was found in 2018, when the lead author of the study was still an undergraduate student. The expedition, led by Peruvian paleontologist Rodolfo Salas-Gismondi, former postdoctoral fellow at the Department of Paleontology at UZH, traversed more than 300 kilometers of the Napo River.
Dozens of fossils were discovered and collected, but the biggest surprise waited at the end of the expedition, after almost three weeks of exploration: the discovery of the large dolphin skull, catalogued as MUSM 4017, which has been permanently deposited in the Museo de Historia Natural in Lima.

Using data from both mice and humans, a Johns Hopkins Medicine research team has found that a cell surface protein that senses odors and chemicals may be responsible for — and help explain — sex differences in mammalian blood pressure. The unusual connection between such protein receptors and sex differences in blood pressure, reported in the March 20 issue of Science Advances, may lead to a better understanding of long known differences in blood pressure between females and males.
Blood pressure in premenopausal human and mouse females is typically 10 points lower in both diastolic and systolic pressure than in males. Some studies suggest the difference may be caused by sex hormones, but the biological basis for the variation is not entirely clear.
“Despite the well-known differences in blood pressure between females and males, most clinical guidelines have the same thresholds for treatment,” says Jennifer Pluznick, Ph.D., associate professor of physiology at the Johns Hopkins University School of Medicine. “Taking a closer look at the fundamental, scientific basis for sex differences in blood pressure may eventually help clinicians think about blood pressure treatment in new ways.”
Pluznick is a basic scientist who has found unique roles for so-called olfactory receptors in various organs of the body. The tiny proteins on the surface of cells essentially sniff out nearby odors or other chemicals.
The Johns Hopkins team began their studies looking for the locations in the body where a specific olfactory receptor — Olfr558 — is found. Olfr558 is one of three olfactory receptors (out of about 350 total) that are well-conserved by evolution in many mammals, including humans and mice. The human version of the receptor is called OR51E1.
Previously, the Johns Hopkins team found Olfr558 in the kidney, and other studies have located the receptor in other organs, aside from the cells responsible for scent detection in the nose.
For this study, the researchers found the receptor in blood vessel cells in the kidney and in juxtaglomerular granular cells, a type of kidney cell that secretes the hormone renin, which plays a key role in regulating blood pressure.

“This was our first indication that we should take a closer look at the impact of Olfr558 on blood pressure,” says Pluznick.
Next, the team, led by Pluznick and research associate Jiaojiao Xu, Ph.D., measured blood pressure in young female and male mice during active and resting timeframes. Male mice with normal levels of the Olfr558 receptor typically had diastolic and systolic blood pressure 10 points higher than female mice.
However, when the researchers looked at young female and male mice genetically engineered to lack the gene for the Olfr558 receptor, they found that blood pressure increased in female mice but decreased in male mice, such that the sex difference in blood pressure disappeared.
Preliminary data from the Johns Hopkins team point to blood vessel stiffness and renin hormone levels in the blood as potential reasons for the lack of blood pressure variation in mice without the receptor.
The research team also analyzed genomic information on human tissue data stored in the U.K. Biobank, focusing on people with a rare variation in the human version of the olfactory receptor OR51E1. Their analysis showed that females and males younger than 50 with the variant do not show the typical sex-linked differences in blood pressure.
The research team cautioned that their work has not identified a direct molecular signaling pathway that would pin down the link between the olfactory receptor and blood pressure variation. Those studies have yet to be done.

Pluznick’s team will try, in future experiments, to pinpoint the precise cell types that govern the receptor-blood pressure link.
“We hope that improving our understanding of the basic biology of this new link will provide insights on blood pressure regulation for both sexes,” says Pluznick.
Support for this research was provided by the National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases [R56DK107726], the National Institute on Aging [R21AG081683], the American Heart Association Established Investigator Award, the NIHR Cardiovascular Biomedical Centre at Barts and the Queen Mary University of London.
In addition to Pluznick and Xu, researchers who contributed to this study are Rira Choi, Kunal Gupta and Lakshmi Santhanam from Johns Hopkins and Helen Warren from the Queen Mary University of London.

The studies, pulled because of copied data, illustrate the sluggishness of scientific publishers to address serious errors, experts said.Scientists in a prominent cancer lab at Columbia University have now had four studies retracted and a stern note added to a fifth accusing it of “severe abuse of the scientific publishing system,” the latest fallout from research misconduct allegations recently leveled against several leading cancer scientists.A scientific sleuth in Britain last year uncovered discrepancies in data published by the Columbia lab, including the reuse of photos and other images across different papers. The New York Times reported last month that a medical journal in 2022 had quietly taken down a stomach cancer study by the researchers after an internal inquiry by the journal found ethics violations.Despite that study’s removal, the researchers — Dr. Sam Yoon, chief of a cancer surgery division at Columbia University’s medical center, and Changhwan Yoon, a more junior biologist there — continued publishing studies with suspicious data. Since 2008, the two scientists have collaborated with other researchers on 26 articles that the sleuth, Sholto David, publicly flagged for misrepresenting experiments’ results.One of those articles was retracted last month after The Times asked publishers about the allegations. In recent weeks, medical journals have retracted three additional studies, which described new strategies for treating cancers of the stomach, head and neck. Other labs had cited the articles in roughly 90 papers.A major scientific publisher also appended a blunt note to the article that it had originally taken down without explanation in 2022. “This reuse (and in part, misrepresentation) of data without appropriate attribution represents a severe abuse of the scientific publishing system,” it said.Still, those measures addressed only a small fraction of the lab’s suspect papers. Experts said the episode illustrated not only the extent of unreliable research by top labs, but also the tendency of scientific publishers to respond slowly, if at all, to significant problems once they are detected. As a result, other labs keep relying on questionable work as they pour federal research money into studies, allowing errors to accumulate in the scientific record.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

Published48 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, PA MediaBy Chas GeigerPolitical reporterA call for the government to back a move to outlaw the abortion after 24 weeks of foetuses diagnosed with Down’s syndrome has been rejected. Currently, pregnancies involving foetuses with Down’s syndrome can be terminated up to the point of birth.Conservative MP Sir Liam Fox is leading a cross-party campaign to bring the time limit into line with foetuses without serious disabilities. Rishi Sunak said votes on abortion had always been a “matter of conscience”.Leading charity the Down’s Syndrome Association (DSA), which champions the rights of people with Down’s syndrome, has called for a review of the law in light of the advances in medical science and testing options now available.”People must have the relevant information to enable them to make an informed choice and the law must reflect the medical science available,” it says. During Prime Minister’s Questions, Sir Liam described it as “an anomaly in the law” that, while the time limit for most UK abortions was 24 weeks into pregnancy, it was “up to full term” where Down’s Syndrome was diagnosed. The former cabinet minister said he would be putting forward an amendment to the Criminal Justice Bill, currently going through Parliament, “to equalise the time limit in line with our disability and equality legislation”. Woman with Down’s syndrome loses abortion law appealDown’s syndrome legislation ‘gives people a voice’Line of Duty star takes on Hollywood with his own script”Surely we can not accept in the 21st century that people with Down’s syndrome are second-class citizens in our country? Will the prime minister support the change?” he asked. Mr Sunak replied it had “been longstanding convention that it would be for Parliament to decide whether to make any changes to the law on abortion and these issues have always been treated as an individual matter of conscience” – indicating that any Commons vote should be a “free” one, independent of party affiliation. In November 2022, a woman with Down’s syndrome lost a legal challenge to the existing law – the 1967 Abortion Act as amended by the 1990 Human Fertilisation and Embryology Act – when judges at the Court of Appeal decided it did not interfere with the rights of living disabled people.Heidi Crowter argued that the rules discriminated against people with Down’s syndrome and “doesn’t respect my life”. She later said she would take her case to the European Court of Human Rights. Down’s syndrome results from being born with an extra chromosome, usually by chance because of a change in the sperm or egg before birth. There are estimated to be around 47,000 people with Down’s syndrome in the UK. According to the DSA, people who have Down’s syndrome will have some level of learning disability, but also a range of abilities. “Some people will be more independent and do things like get a job. Other people might need more regular care,” it says. As the law stands in England, Wales and Scotland, doctors can authorise an abortion if “there is a substantial risk that if the child were born it would suffer from such physical or mental abnormalities as to be seriously handicapped”, meaning that if a foetus is found to have Down’s syndrome, the pregnancy can be terminated after 24 weeks.Sir Liam, who worked as a GP before entering Parliament, has a long-standing interest in Down’s syndrome issues. In 2022, a private member’s bill he introduced passed into law, the Down Syndrome Act. It recognised people with Down’s syndrome as a specific minority group and made it a statutory duty that their specific social care needs were met.More on this storyWoman with Down’s syndrome loses abortion law appealPublished25 November 2022Down’s syndrome legislation ‘gives people a voice’Published2 April 2022’See the person behind the extra chromosome’Published23 September 2021

Published1 hour agoShareclose panelShare pageCopy linkAbout sharingImage source, PA MediaBy Sam HancockBBC NewsThe hospital where Catherine, Princess of Wales, underwent abdominal surgery has said “any breach” of patient information would be investigated. It follows reports that staff tried to access her private medical information.The London Clinic – frequently used by royals – said it had “no place” for those intentionally breaching the trust of patients or colleagues.Earlier, the Information Commissioners’ Office said it had received a “breach report” and was making inquiries.Al Russell, chief executive of the London Clinic, said in a statement that all his employees were “acutely aware” of their “individual, professional, ethical and legal duties with regards to patient confidentiality”.”We take enormous pride in the outstanding care and discretion we aim to deliver for all our patients that put their trust in us every day,” he continued.”We have systems in place to monitor management of patient information and, in the case of any breach, all appropriate investigatory, regulatory and disciplinary steps will be taken.”On Tuesday, the Daily Mirror reported that “at least one member of staff was said to have been caught trying to access” Catherine’s medical notes.The paper said an internal investigation had been launched at the private hospital, which has treated both the princess and King Charles III in recent months.Mr Russell’s statement made no direct reference to the claims about the Princess of Wales.Image source, PA MediaThe UK’s privacy and data protection watchdog has already confirmed receipt of a so-called breach report.In a statement, the Information Commissioners’ Office (ICO) said it was “assessing the information provided”.The Data Protection Act 2018 makes it a criminal offence in the UK to knowingly or recklessly obtain, disclose or retain personal data without the consent of the data controller.This specific part of the law was most commonly used to prosecute those who had accessed healthcare and financial records without a legitimate reason, according to the Crown Prosecution Service (CPS).When asked about the alleged breaches at the London Clinic, Downing Street said there were clearly “strict rules on patient data that must be followed”.”I think we all want to get behind the Princess of Wales, and indeed the Prince of Wales, and we obviously wish her the speediest of recoveries,” the prime minister’s official spokesman added. Catherine had abdominal surgery in January, spending almost two weeks at the London Clinic, and has stepped back from public duties while she recovers.Kensington Palace previously said she would take time away from public-facing engagements until after Easter.But the princess’s absence has led to weeks of online speculation and conspiracy theories about her health.At the end of February, her husband William unexpectedly withdrew from a memorial service for his godfather – with a “personal matter” being blamed. Despite assurances from Catherine’s spokesperson that “the timelines of the princess’s recovery” had been made clear, curiosity around her whereabouts grew – particularly on social media. This came to a head in early March when an image of Catherine and her three children was posted on the official X account of the Prince and Princess of Wales, to mark Mother’s Day. It was found to have been edited, leading to picture services around the world withdrawing it. The princess subsequently apologised “for any confusion”, saying she “occasionally” experimented with editing photographs.On Monday, a blurry video of Catherine and William leaving a farm shop was published by the Sun newspaper but instead of quelling suspicion, the footage has seemed to fuel it. Social media users suggested the woman in the video was in fact a body double, but there was no evidence to suggest this was the case. Kensington Palace has not denied the royal couple’s outing, a trip clearly intended to be private.Sign up to the BBC News Royal Watch newsletter for insider stories and expert analysis each weekMore on this storyHow Kate body-double conspiracy theory spread on social mediaPublished22 hours agoWhy William and Kate video won’t stop online rumoursPublished23 hours agoCan royals move on from Kate photo media storm?Published12 MarchWhat alterations might have been made to Kate’s photo?Published11 March

Researchers at Fred Hutchinson Cancer Center have found that a specific subtype of a microbe commonly found in the mouth is able to travel to the gut and grow within colorectal cancer tumors. This microbe is also a culprit for driving cancer progression and leads to poorer patient outcomes after cancer treatment.
The findings, published March 20 in the journal Nature, could help improve therapeutic approaches and early screening methods for colorectal cancer, which is the second most common cause of cancer deaths in adults in the U.S. according to the American Cancer Society.
Examining colorectal cancer tumors removed from 200 patients, the Fred Hutch team measured levels of Fusobacterium nucleatum, a bacterium known to infect tumors. In about 50% of the cases, they found that only a specific subtype of the bacterium was elevated in the tumor tissue compared to healthy tissue.
The researchers also found this microbe in higher numbers within stool samples of colorectal cancer patients compared with stool samples from healthy people.
“We’ve consistently seen that patients with colorectal tumors containing Fusobacterium nucleatum have poor survival and poorer prognosis compared with patients without the microbe,” explained Susan Bullman, Ph.D., Fred Hutch cancer microbiome researcher and co-corresponding study author. “Now we’re finding that a specific subtype of this microbe is responsible for tumor growth. It suggests therapeutics and screening that target this subgroup within the microbiota would help people who are at a higher risk for more aggressive colorectal cancer.”
In the study, Bullman and co-corresponding author Christopher D. Johnston, Ph.D., Fred Hutch molecular microbiologist, along with the study’s first author Martha Zepeda-Rivera, Ph.D., a Washington Research Foundation Fellow and Staff Scientist in the Johnston Lab, wanted to discover how the microbe moves from its typical environment of the mouth to a distant site in the lower gut and how it contributes to cancer growth.
First they found a surprise that could be important for future treatments. The predominant group of Fusobacterium nucleatum in colorectal cancer tumors, thought to be a single subspecies, is actually composed of two distinct lineages known as “clades.”
“This discovery was similar to stumbling upon the Rosetta Stone in terms of genetics,” Johnston explained. “We have bacterial strains that are so phylogenetically close that we thought of them as the same thing, but now we see an enormous difference between their relative abundance in tumors versus the oral cavity.”

By separating out the genetic differences between these clades, the researchers found that the tumor-infiltrating Fna C2 type had acquired distinct genetic traits suggesting it could travel from the mouth through the stomach, withstand stomach acid and then grow in the lower gastrointestinal tract. The analysis revealed 195 genetic differences between the clades.
Then, comparing tumor tissue with healthy tissue from patients with colorectal cancer, the researchers found that only the subtype Fna C2 is significantly enriched in colorectal tumor tissue and is responsible for colorectal cancer growth.
Further molecular analyses of two patient cohorts, including over 200 colorectal tumors, revealed the presence of this Fna C2 lineage in approximately 50% of cases.
The researchers also found in hundreds of stool samples from people with and without colorectal cancer that Fna C2 levels were consistently higher in colorectal cancer.
“We have pinpointed the exact bacterial lineage that is associated with colorectal cancer, and that knowledge is critical for developing effective preventive and treatment methods,” Johnston said.
He and Bullman believe their study presents significant opportunities for developing microbial cellular therapies, which use modified versions of bacterial strains to deliver treatments directly into tumors.

Short-term exposure to higher heat may increase inflammation and interfere with normal immune system functions in the body, which may, in turn, increase susceptibility to infections and accelerate the progression of cardiovascular disease, according to preliminary research to be presented at the American Heart Association’s Epidemiology and Prevention — Lifestyle and Cardiometabolic Scientific Sessions 2024, March 18- 21, in Chicago.
Inflammation is a normal part of the body’s defenses against injury or infection, however, an inflammatory response that is longstanding — lasting weeks to months — or that occurs in healthy tissues is damaging and plays a key role in the build-up of plaque in the arteries. This may lead to atherosclerosis. Heat waves are known to promote inflammation, however, studies examining air temperature and biomarkers of inflammation have had mixed results.
“Most research only considers temperature as the exposure of interest, which may not be adequate to capture a person’s response to heat,” said lead study author Daniel W. Riggs, Ph.D., an assistant professor of medicine in the Christina Lee Brown Envirome Institute at the University of Louisville in Louisville, Kentucky. “In our study, we used alternative measurements of heat in relation to multiple markers of inflammation and immune response in the body to investigate the short-term effects of heat exposure and produce a more complete picture of its health impact.”
Participants visited study sites in Louisville during the summer months for a blood test, and researchers analyzed the blood for multiple markers of immune system function. The researchers then examined associations between the markers of immune system function and heat levels, including temperature, net effective temperature (which factors in relative humidity, air temperature and windspeed) and the Universal Thermal Climate Index (UTCI) on that day. UTCI is a thermo-physiological model developed by the International Society of Biometeorology Commission that factors in temperature, humidity, wind speed and ultraviolet radiation levels, which was used to evaluate participant’s physical comfort.
The analysis found: For every 5-degree increase in UTCI (in this study, the equivalent of going from a day with no thermal stress to a day with moderate thermal stress, Riggs said), there was an increase in the levels of key markers of inflammation: monocytes (4.2%), eosinophils (9.5%), natural killer T-cells (9.9%) and tumor necrosis factor-alpha (7.0%) in the blood. These immune molecules indicate activation of the body’s innate immune system, which spurs a fast and non-specific inflammatory response throughout the body to protect against pathogens and injury. A decrease in B-cells (-6.8%), indicating the body’s adaptive immune system that remembers specific viruses and germs and creates antibodies to fight them, was lowered. A lesser impact on the immune system was found when heat was measured by average 24-hour temperature or by net effective temperature, which incorporates humidity and wind but not sunshine.”Our study participants only had minor exposure to high temperatures on the day of their blood test, however, even minor exposure may contribute to changes in immune markers,” Riggs said. “With rising global temperatures, the association between heat exposure and a temporarily weakened response from the immune system is a concern because temperature and humidity are known to be important environmental drivers of infectious, airborne disease transmission. Thus, during the hottest days of summer people may be at higher risk of heat exposure, they may also be more vulnerable to disease or inflammation.”
Adults older than age 60 and adults with existing cardiovascular disease are particularly at risk for heat-related cardiovascular events and deaths, Riggs explained. During heat waves, people can reduce their exposure by staying indoors when temperatures are highest and the sun is strongest; seeking shade; wearing light, breathable clothing; and drinking plenty of water.
“It’s important for physicians to communicate with patients about the risk of adverse health effects from heat exposure. For example, cardiologists could conduct customized consultations and assessments to increase patient awareness about their susceptibility to the effects of high temperatures. Also, changes to treatment regimens may be important to consider to address other risks. For example, some medications could make people more susceptible to heat-related illness or some may not be as effective when the body is exposed to high temperatures,” Riggs said.
Study details and background: Participants included 624 adults. The average age of participants was 49.5 years; 59% of participants were women; and 77% self-identified as white race. Data was collected in Louisville, Kentucky, from May through September of 2018 and 2019. The average 24-hour temperature on clinic visit days during the study time period was 24.5 degrees Celsius /76 degrees Fahrenheit. Researchers examined participants’ blood levels of cytokines (signaling molecules that may lead to inflammation); natural killer cells and tumor necrosis factor-alpha; monocytes (white blood cells); and B cells (white blood cells that produce antibodies to fight specific infections). Heat data, collected on the same day that participants’ blood was drawn, included 24-hour averages of temperature, net effective temperature and UTCI. Researchers analyzed the associations between increasing heat metrics and changes in immune system measures. The results were adjusted for several individual factors, including the participants’ age, current tobacco use and years of education.The study’s main limitation is that it includes participants’ blood test for one single point in time. Additionally, the researchers did not know how long individuals were exposed to outdoor heat stress before their blood was drawn. Future research will include a study design to observe changes over a period of time and possibly to examine the ability of green spaces like parks to reduce the harmful effects of high temperatures on inflammation in the body.