A secondary analysis of a trial of 2.4mg semaglutide (Wegovy) found nearly half of the teenage participants with obesity returned to normal weight or fell below the obesity threshold. The trial, results of which were published in Obesity, added semaglutide to dietary advice and a daily goal of 60 minutes of moderate- to high-intensity physical activity.
During the 68-week STEP TEENS trial, 44.9% of participants (aged 12–18 with obesity) returned to either normal weight or went down to the overweight category while on treatment compared with only 12.1% of those on placebo. At the end of the trial, 25% of the treatment group dropped to normal weight compared to just 2% for placebo.
“These results underscore the high degree of clinical effectiveness of semaglutide in adolescents with obesity,” said first author Aaron S. Kelly, PhD, in a statement. “In a practical sense, we see that semaglutide reduced weight to a level below what is defined as clinical obesity in nearly 50% of the teens in our trial, which is historically unprecedented with treatments other than bariatric surgery.”
An ‘important piece to the puzzle’ of the obesity problem
“A question I get a lot is, ‘Is this going to solve the obesity problem? Should we just give it to everybody’?” said Kelly, who is at the University of Minesota. “No and no. It’s not going to solve the obesity problem, but it’s an important piece to the puzzle in helping to solve it, especially for those who already have obesity.”
The trial’s initial results saw a an average BMI reduction 16.1% with semaglutide compared with a 0.6% increase with placebo at week 68. On average, participants on semaglutide lost 15.3 kg, while those on placebo gained 2.4 kg.
“The degree of body weight reduction is unprecedented,” lead study author Daniel Weghuber, MD, of Paracelsus Medical University, told MedPage Today at the ObesityWeek meeting, when the results were presented. “After years of frustration, all of a sudden patients were actually losing weight. They’d never seen that before.”
These results led to the approval for ages 12 and older by the FDA in December 2022, after being approved for adults in June 2021. The study also found a slightly superior but non-significant effect in females than males, despite not being set up to measure sex differences. The same was true for ages 12–14 vs 15–18.
Our body’s own melanin has long held potential as an inspiration for ultra-protective sunscreens, but has been too unstable to properly study. In Nature Chemistry, researchers report a major advance in understanding the fundamental structure of melanin and one of its subunits that turns light into heat, protecting the body from sun damage.
Melanin is the body’s natural pigment that is its first and best natural defence against the damaging effect of ultraviolet radiation. Cosmetics companies have long tried to harness the protective powers of natural and synthetic melanin for use in chemical sunscreens and other personal care products. For example, melanin could, in theory, be used to produce a radiation barrier that augments skin care products by matching a more diverse range of natural skin tones. But melanin is so notoriously unstable and difficult to study that, thus far, scientists have not been able to see what it looks like at the molecular level, resulting in a slow, trial-and-error approach to its potential use in personal care products.
“As we gain a better understanding of the structure of melanin, we should be able to predictably make alternatives that perform better than what is currently available,” said Jean-Philip Lumb, one of the lead authors of the paper. The study found that the melanin component converted light into heat from all wavelengths, spanning the ultraviolet to the infrared, offering a broad spectrum of protection. The molecule was also remarkably small, which the researchers say has practical benefits because the number of atoms needed to provide this level of sun protection is fewer than anything reported up to now. “We’ve taken a major step forward in understanding a new mechanism for how melanin can serve as a sunscreen,” Lumb said.
Researchers at Karolinska Institutet have found further links between Epstein–Barr virus and multiple sclerosis. A study published in Science Advances shows that some individuals have antibodies against the virus that mistakenly attack a protein in the brain and spinal cord.
Many years ago, the Epstein–Barr virus (EBV), which infects most people early in life and then usually lies dormant was linked to multiple sclerosis (MS) but the reason remained a mystery. Increasing evidence, including two papers published in Science and Nature last year, suggests that EBV infection precedes MS and that antibodies against the virus may be involved. However, the molecular mechanisms seem to vary between patients and remain largely unknown.
“MS is an incredibly complex disease, but our study provides an important piece in the puzzle and could explain why some people develop the disease,” says Olivia Thomas, postdoctoral researcher at the Department of Clinical Neuroscience, Karolinska Institutet and shared first author of the paper. “We have discovered that certain antibodies against the Epstein-Barr virus, which would normally fight the infection, can mistakenly target the brain and spinal cord and cause damage.”
The researchers analysed blood samples from more than 700 patients with MS and 700 healthy controls. They found that antibodies that bind to a certain protein in the Epstein-Barr virus, EBNA1, can also bind to a similar protein in the brain and spinal cord called CRYAB, whose role is to prevent protein aggregation during conditions of cellular stress such as inflammation. These misdirected, cross-reactive antibodies may damage the nervous system and cause severe symptoms in MS patients, including problems with balance, mobility and fatigue. The antibodies were present in about 23 percent of MS patients and 7% of control individuals.
“This shows that, whilst these antibody responses are not required for disease development, they may be involved in disease in up to a quarter of MS patients,” says Olivia Thomas. “This also demonstrates the high variation between patients, highlighting the need for personalised therapies. Current therapies are effective at reducing relapses in MS but unfortunately, none can prevent disease progression.”
“We are now expanding our research to investigate how T cells fight EBV infection and how these immune cells may damage the nervous system in multiple sclerosis and contribute to disease progression,” says joint first author of the paper Mattias Bronge, affiliated researcher at the Department of Clinical Neuroscience, Karolinska Institutet.
A registry-based study on cannabis users in Denmark spanning 39 years found that young males were more than twice as likely to develop schizophrenia as young females. The researchers, who published their findings in Psychological Medicine, estimated that about 15% of schizophrenia in this population group is due to cannabis use.
Previous research suggests an increase in schizophrenia population attributable risk fraction (PARF) for cannabis use disorder (CUD). However, sex and age variations in CUD and schizophrenia suggest the importance of examining differences in PARFs in sex and age subgroups.
Moreover, cannabis potency measured by the percentage of delta-9-tetrahydrocannabinol (THC) (main psychoactive component of cannabis) has increased dramatically, eg from 13% in 2006 to 30% in 2016 in Denmark. CUD has also increased markedly – past-year CUD rose significantly from 4.9% in 2014 to 5.9% in 2018 among US 18–25-year-olds.
A growing body of evidence suggests that the relationship between CUD and schizophrenia may differ by sex. Male sex and early heavy or frequent cannabis use are associated with earlier onset of psychosis.
The researchers conducted a nationwide Danish register-based cohort study including all individuals aged 16–49 at some point during 1972–2021, identifying CUD and schizophrenia status.
The researchers examined 6 907 859 individuals, with 45 327 cases of incident schizophrenia during follow-up. Males had slightly higher risk for schizophrenia with CUD (142%) than females (102%). But among 16–20-year-olds, the risk for males (284%) was more than twice that for females (81%). They also found that during the 39-year study period, the annual average increase in PARF for CUD in schizophrenia incidence was 4.8% among males and 3.2% among females. In 2021, among males, this risk fraction was 15%; among females, it was around 4%.
Conclusions
The researchers concluded that “Young males might be particularly susceptible to the effects of cannabis on schizophrenia. At a population level, assuming causality, one-fifth of cases of schizophrenia among young males might be prevented by averting CUD. Results highlight the importance of early detection and treatment of CUD and policy decisions regarding cannabis use and access, particularly for 16–25-year-olds.”
So-called ‘super-recognisers’ are people with a much greater ability to recognise faces in a variety of contexts, but their ability has not been empirically tested. A new study in PNAS shows that super-recognisers do in fact possess greatly superior facial recognition compared to normal peers.
While police departments have known of their abilities for quite some time, it was just over a decade ago, when super-recognisers were described in the literature as having exceptional facial processing abilities. With the increasing use of CCTV in police investigations and the potential for human error, there have been questions raised as to whether super-recognisers could do a better job – or indeed, whether they have empirically superior abilities. A means for actually identifying and defining a super-recogniser as opposed to someone who merely seems to better at recalling faces is therefore needed.
The performance of people with normal facial recognition abilities is not very impressive. While performance is good when people are familiar with the person pictured, studies report an error as high as 35% with unfamiliar faces. Even when people are asked to compare a live person standing in front of them with a photo, a recent study found they still got more than 20% of their answers wrong.
For this study, researchers enrolled 73 super-recogniser and 45 control participants. They compared the two groups on performance on three challenging tests of face identity processing recommended for super-recogniser identification; as well as performance for perpetrator identification using four CCTV sequences depicting five perpetrators and police line-ups created for criminal investigation purposes. They found that the face identity processing tests used here are valid in measuring such abilities and identifying super-recognisers. In addition, they determined that super-recognisers excel at perpetrator identification relative to control participants, with more correct perpetrator identifications, the better their performance across lab tests.
Among a variety of diets a low-calorie ‘green’ Mediterranean diet caused the biggest reduction in aortic stiffness among overweight or dyslipidaemic individuals in a post hoc analysis of a randomised trial. The findings were discussed in Journal of the American College of Cardiology.
As its name suggests, the green Mediterranean diet is rich in plant polyphenols and lower in red or processed meat and simple carbohydrates than a typical low-calorie Mediterranean diet.
Controlling for other variables, the green Mediterranean diet reduced proximal aortic stenosis (PAS) by 15%, better than a typical hypocaloric Mediterranean diet (7.3% reduction) or following standard healthy diet guidelines (4.8% reduction).
The study used the unique environment of a remote Israeli nuclear research facility, where the makeup of the staff meals could be closely controlled and monitored. This also created the limitation of having a predominantly male population for the study group.
More than simple weight loss, the green Mediterranean diet may have greater influence on PAS, which as a measure of “the aortic stiffness from the ascending to the proximal descending thoracic aorta, is a distinct marker of vascular aging and a sensitive early predictor of cardiovascular morbidity and mortality risk,” the researchers noted. “Beyond aging, and similarly to atherosclerosis, PAS is sensitive to obesity-related metabolic conditions, specifically metabolic syndrome.”
Breast cancer cells. Image by National Cancer Institute
In what could be a long-missing piece in the puzzle of breast cancer, researchers have identified the molecular sparkplug that ignites cases of the disease currently unexplained by the classical model of breast-cancer development. The team reported their work inNature.
“We have identified what we believe is the original molecular trigger that initiates a cascade culminating in breast tumour development in a subset of breast cancers that are driven by oestrogen,” said study senior investigator Peter Park, Harvard Medical School professor.
The researchers said as many as one-third of breast cancer cases may arise through the newly identified mechanism.
The study also shows that the sex hormone oestrogen is the culprit behind this molecular dysfunction because it directly alters a cell’s DNA.
Most, though not all, breast cancers are fuelled by hormonal fluctuations. The prevailing view of oestrogen’s role in breast cancer is that it acts as a catalyst for cancer growth because it stimulates the division and proliferation of breast tissue, a process that carries the risk for cancer-causing mutations. The new work, however, shows that oestrogen causes mischief in a far more direct manner.
“Our work demonstrates that oestrogen can directly induce genomic rearrangements that lead to cancer, so its role in breast cancer development is both that of a catalyst and a cause,” said study first author Jake Lee.
While the findings does not have immediate therapy applications, it could lead to tests that can track treatment response and could help doctors detect the return of tumours in patients with a history of certain breast cancers.
Birth of a cancer cell
When DNA breaks in the process of cell division, the breaks usually get swiftly mended by the molecular machinery that guards the integrity of the genome. However, every now and then, the repair of broken DNA gets botched, causing chromosomes to get misplaced or scrambled inside a cell.
Many human cancers arise in this manner during cell division, when chromosomes get rearranged and awaken dormant cancer genes that can trigger tumour growth.
One such chromosomal scramble can occur when a chromosome breaks, and a second copy of the broken chromosome is made before the break gets fixed.
Then, in what ends up being a botched repair attempt, the broken end of one chromosome is fused to the broken end of its sister copy rather than to its original partner. The resulting new structure is a misshapen, malfunctioning chromosome.
During the next cell division, the misshapen chromosome is stretched between the two emerging daughter cells and the chromosome “bridge” breaks, leaving behind shattered fragments that contain cancer genes to multiply and get activated.
It has been known since the 1930s that certain human cancers, including some breast cancers, arise when a cell’s chromosomes get rearranged in this way. Cancer experts can often identify this particular aberration in tumour samples by using genomic sequencing. Yet, a portion of breast cancer cases do not harbour this mutational pattern, raising the question: What is causing these tumours?
These ‘cold’ intrigued study authors Park and Lee, who searched for answers by analysing the genomes of 780 breast cancers obtained from patients diagnosed with the disease. They expected to find the classical chromosomal disarray in most of the tumour samples, but many of the tumour cells bore no trace of this classic molecular pattern.
Instead of the classic misshapen and improperly patched-up single chromosome, they saw that two chromosomes had fused, suspiciously near ‘hot spots’ where cancer genes are located.
Just as in McClintock’s model, these rearranged chromosomes had formed bridges, except in this case, the bridge contained two different chromosomes. This distinctive pattern was present in one-third (244) of the tumours in their analysis.
Lee and Park realised they had stumbled upon a new mechanism by which a ‘disfigured’ chromosome is generated and then fractured to fuel the mysterious breast cancer cases.
A new role for oestrogen in breast cancer?
When the researchers zoomed onto the hot spots of cancer-gene activation, they noticed that these areas were curiously close to oestrogen-binding areas on the DNA.
Oestrogen receptors are known to bind to certain regions of the genome when a cell is stimulated by oestrogen. The researchers found that these oestrogen-binding sites were frequently next to the zones where the early DNA breaks took place.
This offered a strong clue that oestrogen might be somehow involved in the genomic reshuffling that gave rise to cancer-gene activation.
Lee and Park followed up on that clue by exposing breast cancer cells to oestrogen and then used CRISPR gene editing to make cuts to the cells’ DNA.
As the cells mended their broken DNA, they initiated a repair chain that resulted in the same genomic rearrangement Lee and Park had discovered in their genomic analyses.
Oestrogen is already known to fuel breast cancer growth by promoting the proliferation of breast cells. However, the new observations cast this hormone in a different light. They show oestrogen is a more central character in cancer genesis because it directly alters how cells repair their DNA.
The findings suggest that oestrogen-suppressing drugs such as tamoxifen work in a more direct manner than simply reducing breast cell proliferation.
“In light of our results, we propose that these drugs may also prevent oestrogen from initiating cancer-causing genomic rearrangements in the cells, in addition to suppressing mammary cell proliferation,” Lee said.
The study could lead to improved breast cancer testing. For instance, detecting the genomic fingerprint of the chromosome rearrangement could alert oncologists that a patient’s disease is coming back, Lee said.
A similar approach to track disease relapse and treatment response is already widely used in cancers that harbour critical chromosomal translocations, including certain types of leukaemia.
More broadly, the work underscores the value of DNA sequencing and careful data analysis in deepening the biology of cancer development, the researchers said.
“It all started with a single observation. We noticed that the complex pattern of mutations that we see in genome sequencing data cannot be explained by the textbook model,” Park said. “But now that we’ve put the jigsaw puzzle together, the patterns all make sense in light of the new model. This is immensely gratifying.”
With growing legalisation and recreational use of cannabis comes a change in attitudes. Research has shown that dispensaries often recommend cannabis for the easing of pregnancy symptoms, especially morning sickness.
Growing evidence links cannabinoid consumption during pregnancy with poor child outcomes, though the exact effects on the developing foetus remain unclear. In a study published in Frontiers in Pediatrics, researchers in the US have now examined how timing of cannabis exposure during pregnancy impacts foetal development.
“We show that even when marijuana use occurred only in the first trimester of pregnancy, birth weight was significant reduced, by more than 150g on average,” said senior author Dr Beth Bailey, professor and director of population health research at Central Michigan University. “If that use continued into the second trimester, newborn head circumference was significantly decreased as well.”
Continued exposure results in largest deficiencies
“These findings are important as newborn size is one of the strongest predictors of later child health and development,” added study first author Dr Phoebe Dodge.
Recent work, including the research by Dodge et al., has shown significant effects of cannabis use on newborn size. “Size deficits were largest among newborns exposed to marijuana throughout gestation,” Bailey explained. The babies born after continued in-utero exposure were nearly 200g lighter, and their head circumference was nearly 1cm less than that of babies who had not been exposed. Pregnancy cannabis use did not significantly predict newborn length in this study.
The effects the scientists observed have also shed light on patterns of use. Their study showed that occasional use, such as for first trimester morning sickness, may reduce fetal growth in the same way as continued use throughout pregnancy. The same is true for other use in early stages, including cases when someone uses cannabis not knowing they are pregnant.
Quitting before pregnancy is best recommendation
The authors pointed out that in their study they did not have information about how much or how often participants used cannabis. Their results were based on whether people did or did not use it at certain times in pregnancy. Therefore, the study could not establish if there was a connection between heavy use and more pronounced outcomes in newborn growth.
More studies are needed to determine whether timing or amount of use is most important when it comes to effects on newborn size, they wrote.
“The best recommendation is that women should be advised to quit marijuana use prior to becoming pregnant,” Dodge said. However, quitting as soon as possible after getting pregnant is the second-best option to avoid long term adverse health and developmental outcomes. “There are some benefits of quitting among those who begin pregnancy using marijuana,” she continued.
Researchers report in Nature Ecology and Evolution that human DNA traces can be found nearly everywhere, short of isolated islands and remote mountaintops. That ubiquity is both a scientific boon and an ethical dilemma, say the University of Florida researchers who sequenced this ‘errant’ DNA. The DNA was of such high quality that the scientists could identify mutations associated with disease and determine the genetic ancestry of nearby populations. They could even match genetic information to individual participants who had volunteered to have their errant DNA recovered.
David Duffy, the UF professor of wildlife disease genomics who led the project, says that ethically handled environmental DNA samples could benefit fields from medicine and environmental science to archaeology and criminal forensics. For example, researchers could track cancer mutations from wastewater or spot undiscovered archaeological sites by checking for hidden human DNA. Or detectives could identify suspects from the DNA floating in the air of a crime scene.
But this level of personal information must be handled extremely carefully. Now, scientists and regulators must grapple with the ethical dilemmas inherent in accidentally — or intentionally — sweeping up human genetic information, not from blood samples but from a scoop of sand, a vial of water or a person’s breath.
The paper by Duffy’s group outlines the relative ease of collecting human DNA nearly everywhere they looked.
“We’ve been consistently surprised throughout this project at how much human DNA we find and the quality of that DNA,” Duffy said. “In most cases the quality is almost equivalent to if you took a sample from a person.”
Because of the ability to potentially identify individuals, the researchers say that ethical guardrails are necessary for this kind of research. The study was conducted with approval from the institutional review board of UF, which ensures that ethical guidelines are adhered to during research studies.
“It’s standard in science to make these sequences publicly available. But that also means if you don’t screen out human information, anyone can come along and harvest this information,” Duffy said. “That raises issues around consent. Do you need to get consent to take those samples? Or institute some controls to remove human information?”
Duffy’s team at UF’s Whitney Laboratory for Marine Bioscience and Sea Turtle Hospital has successfully used environmental DNA, or eDNA, to study endangered sea turtles and the viral cancers they are susceptible to. They’ve plucked useful DNA out of turtle tracks in the sand, greatly accelerating their research program.
The scientists knew that human eDNA would end up in their turtle samples and probably many other places they looked. With modern genetic sequencing technology, it’s now straightforward to sequence the DNA of every organism in an environmental sample. The questions were how much human DNA there would be and whether it was intact enough to harbor useful information.
The team found quality human DNA in the ocean and rivers surrounding the Whitney Lab, both near town and far from human settlement, as well as in sand from isolated beaches. In a test facilitated by the National Park Service, the researchers traveled to part of a remote island never visited by people. It was free of human DNA, as expected. But they were able to retrieve DNA from voluntary participants’ footprints in the sand and could sequence parts of their genomes, with permission from the anonymous participants.
Duffy also tested the technique in his native Ireland. Tracing along a river that winds through town on its way to the ocean, Duffy found human DNA everywhere but the remote mountain stream where the river starts, far from civilization.
The scientists also collected room air samples from a veterinary hospital. They recovered DNA matching the staff, the animal patient and common animal viruses.
Now that it’s clear human eDNA can be readily sampled, Duffy says it’s time for policymakers and scientific communities to take issues around consent and privacy seriously and balance them against the possible benefits of studying this errant DNA.
“Any time we make a technological advance, there are beneficial things that the technology can be used for and concerning things that the technology can be used for. It’s no different here,” Duffy said. “These are issues we are trying to raise early so policy makers and society have time to develop regulations.”
The US National Institutes of Health is funding a new clinical trial of an oral anti-radiation treatment. So-called dirty bombs are nuclear weapons that release a cloud of radioactive isotopes, and are thought to be an attractive option for terrorists because they are far easier to build than true nuclear explosives.
In such a situation, as well as a nuclear accident, the danger is not so much from direct radiation in the form of X-rays, gamma rays and alpha and beta particles, but from radioactive materials which are absorbed into the body via contaminated air, food or water. Certain radioisotopes from radioactive fallout are readily absorbed by the body, and cause damage to DNA and cellular structures. Current treatment contain chemicals that bind to these radioisotopes, preventing them from being taken up by the body and instead rapidly excreted.
The Food and Drug Administration has approved two products for removing internal radioactive contamination. These drugs, both based on diethylenetriamine pentaacetate (DTPA), are administered intravenously by a healthcare provider and can remove three radioactive elements: plutonium, americium, and curium.
In contrast, HOPO 14-1 is an oral capsule, which would be easier than an intravenous drug to stockpile and to deploy and administer during an emergency. Preclinical research has shown that HOPO 14-1 can effectively remove many radioactive contaminants, including uranium and neptunium in addition to plutonium, americium and curium. These studies also have found that HOPO 14-1 is up to 100 times more effective than DTPA at binding and removing these radioactive elements.
The trial will seek 42 healthy volunteers aged 18 to 65, who will of course not be exposed to radioactive fallout. They will be assigned into seven groups of six. Each participant in the first group will receive a 100-milligram (mg) dose of HOPO 14-1. The subsequent groups will receive increasingly higher doses of the study drug up to 7500 mg in the final group, if lower doses are deemed safe. Participants will undergo intensive safety monitoring and will be followed for 14 days to measure the absorption, distribution and elimination of the study drug. Results are expected in 2024.
