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Published2 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Shaun Whitmore/BBCBy Alex Dunlop and Charlie JonesBBC East Lip fillers have grown increasingly popular but the industry is “like the wild west”, experts warn, with many patients left in pain and embarrassed by their appearance.As Harriet Green left a salon after getting an injection to add volume to her lips, she was reassured the excess swelling would go down.But three months later her lips were still so bloated she could not close her mouth properly.The 22-year-old from Acle in Norfolk needed three corrective procedures – costing a total of more than £700 – to get them back to normal.”My lips were so uncomfortable. I couldn’t put them together because I had two really hard lumps,” she says.Image source, Harriet GreenHarriet, who works as a customer services call handler, had never had a cosmetic procedure before getting the treatment in December.After seeing influencers promoting jaw fillers, anti-wrinkle injections and lip fillers on Instagram and TikTok, she decided to get her lips enhanced, hoping it would fix “a small insecurity” she felt about them.”With the standards of our generation and social media these days, I just thought I wanted it done. There is this massive pressure and so much talk about it. It just seems like the normal thing to do,” she says.But Harriet now realises the industry is “a minefield” and photos on social media “don’t always show you the reality”.”It’s really scary. You don’t always see the final result after a few months. When I smile I feel just as insecure now as I did before, if not more,” she added. ‘It’s becoming more and more of a problem’Image source, Shaun Whitmore/BBCThe initial treatment cost £165 but Harriet has now paid more than £700 to get her lips corrected by Dr Saba Raja, a GP who runs her own aesthetics clinic in Norwich. Dr Raja is increasingly having to correct treatments which have gone wrong, she says, describing the experience as “really distressing”.”Every month I’m getting enquires from young girls who have gone to a non-medical practitioner for lip or tear trough fillers under the eye and had complications.”They often try to contact the practitioner but due to lack of training they are unable to deal with the complications. It is becoming more and more of a problem.”Dr Raja describes the industry as “like the wild west”, with people injecting patients “out of the back of their cars” and in kitchens.”Anti-wrinkle injections (Botox) are prescription-only but the injector can be anybody who has been on a day course. Dermal filler (for the lips and face) is not even a prescription-only medication, you can buy it off any website,” she says.”A lot of non-medical practitioners are buying cheap filler online, with no idea where it has come from. We really need strict regulations and minimum training standards.”Image source, Shaun Whitmore/BBCThe British College of Aesthetic Medicine’s annual survey found that 82% of its 400 members treated patients with complications caused by another provider last year.Nearly 2,000 of the reported complications, which is 59%, came from treatments performed by beauticians, it found. Dermal fillers caused the most complications, with three reported for every 1,000 treatments last year, compared to 1.5 in 1,000 treatments in 2021. “This confirms how dangerous dermal fillers can be in the wrong hands,” the report adds.’Permanent blindness is a risk’Image source, Dr Tamara GriffithsDr Tamara Griffiths of the British Association of Dermatologists believes dermal fillers are a particular problem because “anyone can inject them” and they are “higher risk” than other cosmetic procedures.”Permanent blindness is one of the potential risks. It is rare but there have been cases cited in the UK,” she says.Vascular occlusion is another potential complication, where a blood vessel blockage prevents blood from moving through pathways in your body. Dermatologists have been concerned about the “very unregulated and potentially very dangerous sector” for more than a decade, she adds.”There is a cohort of increasingly fly-by-night people who inject, who are there on Instagram one day and gone the next, who are frankly fraudulent in claiming their qualifications.”People who want a cosmetic procedure must do their own research and see someone who is reputable, on the voluntary register and belongs to a professional body, she adds.Earlier this year the government rejected a call by MPs to bring forward a mandatory licensing scheme to regulate non-surgical cosmetic procedures in England.Ministers also rejected recommendations to make dermal fillers available on a prescription-only basis, in line with Botox.The Department of Health and Social Care says it is still working on the scheme which will make it an offence to carry out specified non-surgical procedures without a licence and it will carry out a consultation this summer.”Anyone considering a cosmetic procedure should reflect fully on the possible impact of the procedure on both their physical and mental health and, if they decide to go ahead, take the time to find a reputable, insured and qualified practitioner,” a spokesperson said.For Harriet, the scheme will come too late but after three procedures she is finally happy with her lips and trying to rebuild her confidence. She hopes by sharing her experience she can encourage other women to make more informed choices.”If you’re going to get lip filler, or anything, do your research before and don’t just go by social media pictures because it doesn’t mean anything,” she adds.Find BBC News: East of England on Facebook, Instagram and Twitter. If you have a story suggestion email eastofenglandnews@bbc.co.ukMore on this story’My lip filler treatment went badly wrong’18 December 2019I got lip fillers when I was 1610 December 2021Kylie Jenner: I’ve had lip fillers7 May 2015Lauren Goodger has lip fillers removed15 June 2016’Irresponsible’ ad for lip fillers banned27 February 2019I’ve fixed my botched lip filler19 December 2018

Published2 hours agoShareclose panelShare pageCopy linkAbout sharingBy Naomi GrimleyGlobal Health CorrespondentKnocking on doors to check on people’s health and catch problems before they escalate is common practice across Brazil. But could that approach work in the UK?Comfort and Nahima are on their regular beat around Churchill Gardens, a council estate in the Pimlico neighbourhood of London.Dressed in blue fleeces with logos, they steadily climb the concrete staircases of each block on the estate. Comfort, a retired nurse, is off to see 88-year-old Stanley Smithson. He says “loneliness is a very frightening aspect of old age” which he had not anticipated until one of his daughters moved to New Zealand. He jokes Comfort’s visits are exactly that – a comfort. “She’s keeping an eye on me. I notice she’s discreetly taking notes because she’s making her own observations,” he said.”And then – before I know it – I’m being asked to go into the surgery for a blood test or something.”Comfort and Nahima are two out of four door-knockers on this small patch, visiting residents as part of a proactive community healthcare pilot. They can help with anything from housing issues which impact health, such as overcrowding, or pick up the early signs of diabetes by chatting informally to residents about their lifestyle. It is an approach to healthcare which has been successful in the poorer parts of Brazil.Comfort can give practical assistance too – she once helped Stanley get handrails fixed in his bathroom after he had a hip operation. She points out the job is supposed to have a broad remit. “We’re not just talking about health. We go beyond health. We can liaise with housing and we’ll talk about anything and everything,” she said.Above all, she has time to listen which she says GPs do not always have given the strict time limit on appointments. Nahima is also going house to house and is not deterred by sometimes having the odd door slammed in her face. She says it is a job that requires patience but she has already seen a concrete way her role can make a difference to community health after she solved the puzzle of why the estate had low take-up of cervical screening tests. “We had a number of women who, because they come from different ethnic populations, thought that a smear test would cost them money,” she said. “When we started there were quite low numbers coming for smear tests but since then they have shot up.”These community health workers are partly funded by the local authority and partly by the NHS so they can co-ordinate between the local GP surgery and other social services. The National Institute for Health Research helped crunch the data from the pilot. Households which had been visited regularly were 47% more likely to have received immunisations and 82% more likely to have taken up cancer screening, compared to other areas. The idea to import this model to the UK came from Dr Matthew Harris, a public health expert at Imperial College London who worked as a GP in Brazil for four years. There, community health workers have been credited with achieving a drop of 34% in cardiovascular deaths. “In Brazil they have scaled this role to such degree that they have 270,000 community health workers across the whole country, each of which looks after 150 households, visiting them at least once a month,” Dr Harris said. “They’ve seen extraordinary outcomes in terms of population health in the last two or three decades. We think we’ve got a lot to learn from that.”At the local surgery in Pimlico, Dr Connie Junghans-Minton is convinced the pilot is having an effect as there are now fewer requests for appointments which do not really need the doctor, such as requests for housing letters. She says she likes the fact that the community healthcare workers are her eyes and ears on the estate. “They have discovered real medical problems in the community which wouldn’t have come to our attention otherwise,” she said. “In the olden days it used to be the village GP who knew everyone, but we don’t have that anymore and we can’t go back to that. This initiative feels to me like it could be a natural way forward.” Already, other areas of the country are copying the project – similar schemes have already been implemented in Calderdale, West Yorkshire, and Warrington, Cheshire, by local primary care networks. Parts of Norfolk and Cornwall are also interested in following suit. It would cost £300m to roll it out in the poorest areas of England, according to Imperial College London, but advocates point out it could save lots of money down the line. More on this storyMillions wait more than a fortnight to see a GP21 April’The phone rings all day – the pressure is huge’4 January

Microbes play important roles in ecosystems, and these roles are changing with global warming. Scientists also now know that most types of microbes are infected by viruses, but they know relatively little about how these viral infections could change how microbes react to warming. In this study, scientists describe many different ways that increasing temperatures could affect viruses and their microbial hosts. These changes could ultimately affect the responses of whole ecosystems to warming. The work exposes several important gaps in researchers’ current knowledge about the connections between viruses, warming, and ecosystem functioning. Filling these gaps is crucial for understanding and predicting the effects of climate change on ecosystems.
This study creates a roadmap for understanding the many different ways that viruses could modify the effects of warming on communities of microbes. Viruses likely have strong effects on processes with microbes and the ways ecosystems function. Incorporating these previously ignored effects into ecosystem models will help scientists improve their predictions of how ecosystems could respond to climate change.
Microorganisms play integral roles in ecosystems by controlling the flow of energy and matter through processes like photosynthesis (carbon uptake), respiration (carbon release), and decomposition (carbon recycling). Climate change is currently altering how ecosystems function by changing how organisms operate within microbial food webs. Scientists know that viruses can have strong impacts on microbial processes, but they have less knowledge of how these impacts will change with future warming.
In this study, scientists from Duke University, the University of Tennessee Knoxville, the Netherlands Institute of Ecology, and Oak Ridge National Laboratory reviewed the potential impacts of warming on viruses and how these might alter scientific understanding of ecosystem responses to climate change. Warming likely affects several different stages of the viral infection cycle, as well as virus-host dynamics. However, there are still many gaps in our understanding about these effects. Because viruses are ubiquitous across all habitats and have strong effects on microbial functioning, filling these gaps is critical to understanding how warming will affect the flow of energy and matter within ecosystems. The researchers’ preliminary models show that viruses could potentially tip the scales on natural carbon balances, causing some ecosystems to switch from being net carbon sources (releasing more carbon than they store) to being net carbon sinks (absorbing carbon). This study shows how incorporating viruses into predictive models can lead to new and unexpected effects on ecosystems in response to climate change.
This work was supported by the Department of Energy Office of Science, Biological and Environmental Research program.

Researchers from the University of California, Irvine have developed a DNA enzyme — or DNAzyme — that can distinguish between two RNA strands inside a cell and cut the disease-associated strand while leaving the healthy strand intact. This breakthrough “gene silencing” technology could revolutionize the development of DNAzymes for treating cancer, infectious diseases and neurological disorders.
DNAzymes are nucleic acid enzymes that cut other molecules. Through chemistry, UCI’s team developed the Dz 46 enzyme, which specifically targets the allele-specific RNA mutation in the KRAS gene, the master regulator of cell growth and division, found in 25 percent of all human cancers. A description of how the team achieved this enzyme evolution was recently published in the online journal Nature Communications.
“Generating DNAzymes that can effectively function in the natural conditions of cell systems has been more challenging than expected,” said corresponding author John Chaput, UCI professor of pharmaceutical sciences. “Our results suggest that chemical evolution could pave the way for development of novel therapies for a wide range of diseases.”
Gene silencing has been available for more than 20 years and some FDA-approved drugs incorporate various versions of the technology, but none can distinguish a single point mutation in an RNA strand. The benefit of the Dz 46 enzyme is that it can identify and cut a specific gene mutation, offering patients an innovative, precision medicine treatment.
The DNAzyme resembles the Greek letter omega and acts as a catalyst by accelerating chemical reactions. The “arms” on the left and right bind to the target region of the RNA. The loop binds to magnesium, and folds and cuts the RNA at a very specific site. But generating DNAzymes with robust multiple turnover activity under physiological conditions required some ingenuity, because DNAzymes are normally very dependent on concentrations of magnesium not found inside a human cell.
“We solved that problem by re-engineering the DNAzyme using chemistry to reduce its dependency on magnesium and did so in such a way that we could maintain high catalytic turnover activity,” Chaput said. “Ours is one of the very first, if not the first, example of achieving that. The next steps are to advance Dz 46 to a point that it’s ready for pre-clinical trials.”
Team members Kim Thien Nguyen, project scientist, and Turnee N. Malik, postdoctoral scholar, both from the Department of Pharmaceutical Sciences, also participated in this study.
The researchers and UCI have filed provisional patent applications on the chemical composition and cleavage preference of Dz 46. Chaput is a consultant for drug development company 1E Therapeutics, which supported this work.

When you need a bit of motivation, it often has to come from within. New research suggests cancer-fighting immune cells have found a way to do just that.
Scientists at University of California San Diego have discovered a property of T cells that could inspire new anti-tumor therapeutics. Through a previously undescribed form of cell auto-signaling, T cells were shown to activate themselves in peripheral tissues, fueling their ability to attack tumors.
The study, published May 8, 2023 in Immunity, was led by study first author and postdoctoral fellow Yunlong Zhao, PhD, and co-senior authors Enfu Hui, PhD, professor in the School of Biological Sciences at UC San Diego and Jack D. Bui, MD, PhD, professor of pathology at UC San Diego School of Medicine.
T cells are a type of white blood cell that protect against infection and help fight cancer. In the lymph organs, T cells are trained by antigen-presenting cells, which, as their name suggests, present an antigen (a piece of tumor or pathogen) to T cells, stimulating an immune response.
A key part of this process is the binding of B7, a protein on the surface of antigen-presenting cells, with CD28, a receptor on T cells. This B7:CD28 interaction is a major driver of the T cell immune response. Once trained, T cells leave the lymph organs and travel through the body to find and attack their targets.
More recent work has since revealed that T cells can actually produce their own B7 or take the B7 protein from the antigen-presenting cells and bring it along with them, but exactly why they do this has remained unclear. This also led the researchers to wonder whether T cells, now equipped with both a receptor and its ligand, might be able to activate themselves.

Through a series of experiments, the researchers found that T cells could indeed self-activate by puckering their cell membrane inwards to allow the B7 protein and the CD28 receptor to bind each other.
“People often assume the cell membrane is flat, but it actually looks more like a coastline with lots of coves and bays,” said Hui. “We found that local membrane curvatures are actually a rich dimension of T cell auto-signaling, which is paradigm-shifting in a field that assumed this only happened across cells.”
The researchers then confirmed that this auto-stimulation was indeed effective in boosting T cell function and slowing tumor growth in a mouse model of cancer.
“When a T cell exits a lymph organ and enters a tumor environment, it’s like leaving home and going for a long trek in the woods,” said Bui. “The same way a hiker brings snacks to sustain them through the trip, the T cells bring their own signal to keep them going. Now the exciting question is, how much farther will they go if we can provide more food?”
Refueling the T cells could be achieved by either providing more sources of B7 in the lymph organs or in the tumor itself. Another option, the authors say, would be to develop a cell therapy in which engineered T cells with enhanced auto-signaling capabilities were delivered directly to a patient.
The researchers also suggest this system could be used as a cancer biomarker, in that patients whose tumors contain many T cells with B7 may be doing better at fighting the disease.
On the other hand, in patients with autoimmune diseases such as lupus or multiple sclerosis, physicians could prescribe endocytosis inhibitors to prevent the cell from forming concavities, effectively blocking the B7:CD28 interaction to reduce overactive T cell function.
“We’ve found a way that T cells are able to live outside of their normal homes and survive in the foreign environment of a tumor, and we can now develop clinical strategies for increasing or decreasing these pathways to treat disease,” said Hui.
Co-authors include: Yunlong Zhao, Christine Caron, Ya-Yuan Chan, Calvin K. Lee, Xiaozheng Xu, Jibin Zhang and Takeya Masubuchi at UC San Diego, as well as Chuan Wu at the National Cancer Institute.

Scientists at the National Institutes of Health have identified new genetic risk factors for two types of non-Alzheimer’s dementia. These findings were published in Cell Genomics and detail how researchers identified large-scale DNA changes, known as structural variants, by analyzing thousands of DNA samples. The team discovered several structural variants that could be risk factors Lewy body dementia (LBD) and frontotemporal dementia (FTD). The project was a collaborative effort between scientists at the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute on Aging (NIA) at NIH.
Structural variants have been implicated in a variety of neurological disorders. Unlike more commonly studied mutations, which often affect one or a few DNA building blocks called nucleotides, structural variants represent at least 50 but often hundreds, or even thousands, of nucleotides at once, making them more challenging to study.
“If you imagine that our entire genetic code is a book, a structural variant would be a paragraph, page, or even an entire chapter that has been removed, duplicated, or inserted in the wrong place,” said Sonja W. Scholz, M.D., Ph.D., investigator in the neurogenetics branch of NINDS and senior author of this study.
By combining cutting-edge computer algorithms capable of mapping structural variations across the whole genome with machine learning, the research team analyzed whole-genome data from thousands of patient samples and several thousand unaffected controls.
A previously unknown variant in the gene TCPN1 was found in samples from patients with LBD, a disease, that like Parkinson’s disease, is associated with abnormal deposits of the protein alpha-synuclein in the brain. This variant, in which more than 300 nucleotides are deleted from the gene, is associated with a higher risk for developing LBD. While this finding is new for LBD, TCPN1 is a known risk factor for Alzheimer’s disease, which could mean that this structural variant plays a role in the broader dementia population.
“From a genetics standpoint, this is a very exciting finding,” said Dr. Scholz. “It provides a point of reference for cell biology and animal model studies and possibly down the road, a target for intervention.”
By looking at a group of 50 genes implicated in inherited neurodegenerative diseases, the investigators were able to identify additional rare structural variants, including several that are known to cause disease. The analyses also identified two well-established risk factors for FTD changes in the C9orf72 and MAPT genes. These proof-of-concept findings bolstered the strength of the study’s new findings by demonstrating that the algorithms were properly working.
Because reference maps for currently-available structural variants are limited, the researchers generated a catalog based on the data obtained in these analyses. The analysis code and all the raw data are now available to the scientific community for use in their studies. An interactive app also allows investigators to study their genes of interest and ask which variants are present in controls vs. LBD or FTD cases. The authors assert these resources may make complex genetic data more accessible to non-bioinformatics experts, which will accelerate the pace of discovery.
“Research to unravel the intricate genetic architecture of neurodegenerative diseases is resulting in significant advances in scientific understanding,” said Bryan J. Traynor, M.D., Ph.D., senior investigator at NIA. “With each discovery, we shed light on the mechanisms behind neuronal cell death or dysfunction, paving the way for precision medicine to combat these debilitating and fatal disorders.”
Researchers expect that the dataset will continue to grow as additional data are analyzed.
This work was supported in part by the Intramural Research Program at NINDS and NIA.

These health impacts affected communities in states with high oil and gas production, as well as states with limited or no gas activity, underlining the need for comprehensive regulatory action to protect Americans from the pollutants generated by this sector.
Despite global efforts to transition from fossil fuels to clean energy, oil and gas (O&G) production is nearing record levels in the United States, posing concern among health experts about what this O&G growth means for air quality and human health. While there is extensive research on the climate effects of O&G-produced methane — a key contributor to air pollution — few studies have measured the health effects of the air pollution that O&G activity generates.
A new study led by Boston University School of Public Health (BUSPH), the University of North Carolina Institute for the Environment (UNC-IE), PSE Healthy Energy, and Environmental Defense Fund fills this gap.
Published in the journal Environmental Research: Health, the study found that air pollution from the oil and gas sector in the United States has substantial adverse impacts on air quality, human health, and health costs.
The findings show that the pollutants nitrogen oxide (NO2), fine particulate matter (PM2.5) and ozone (O3) from U.S. oil and gas production contributed to 7,500 excess deaths, 410,000 asthma attacks, and 2,200 new cases of childhood asthma across the U.S. in 2016. Factoring in related respiratory and cardiovascular-related hospitalizations, adverse pregnancy outcomes, and other health challenges, oil and gas production was responsible for $77 billion in annual health costs. Comparatively, this total is three times the estimated climate impact costs of methane emissions from oil and gas operations.
These impacts were largely concentrated in areas with significant oil and gas production, such as southwest Pennsylvania, Texas, and Eastern Colorado. But the health effects also extended into densely populated cities with little or no gas activity, such as Chicago, New York City, Baltimore, Washington DC, and Orlando.

The study results suggest that O&G emissions reduction policies, such as the forthcoming EPA methane regulations, may produce immediate and significant air quality benefits to human health along with significant climate benefits. The researchers urge policymakers to consider these “co-benefits” in future emissions reduction strategies. They also stress that strategies that focus on end-of-pipe pollution controls during combustion — such as in power plants, vehicles, buildings, and industry — are only addressing part of the problem.
“These substantial impacts from oil and gas production show that there are serious consequences across the full life cycle of oil and gas, from ‘well to wheels,’ ‘well to power plant,’ and ‘well to furnace,'” says study corresponding author Jonathan Buonocore, assistant professor of environmental health at BUSPH. “The health impacts are not just from the combustion of oil and gas. In order for energy, air quality, and decarbonization policies to successfully protect health, they need to incorporate health impacts across this full life cycle.”
The five states with the highest impacts from O&G pollution were Texas, Pennsylvania, Ohio, Oklahoma, and Louisiana were those with significant oil and gas activity. However, Illinois and New York — states that produce very little O&G — still landed in the 6th and 8th spots.
“The fact that air pollution and health impacts cross state boundaries indicates a strong need for regional to nationwide coordination,” says study senior author Saravanan Arunachalam, research professor at UNC-IE. “States that have the highest emissions are not necessarily always the ones with the highest health risk due to these emissions, although Texas ranks first in both.”
A novelty of this modeling framework is the inclusion of health impacts of NO2, and the use of an advanced model that better captures the chemistry of emissions from the oil & gas sector. Among the three pollutants, NO2 was the highest contributor to the overall health impacts, producing 37 percent of these effects, followed by ozone at 35 percent, and PM2.5 at 28 percent. The vast majority of these effects pertained to mortality. NO2 contributes to the formation of PM2.5 and ozone, so strategies to reduce O&G-produced NO2 could be effective in reducing health impacts. State regulations addressing precursor NO2 emissions from the oil and gas sector could help mitigate childhood asthma cases for communities living in proximity to the emission sources, and provide secondary ozone and PM2.5 health benefits in downwind areas.
“Curbing oil and gas emissions is one of the fastest, most cost-effective ways to reduce methane and other air pollutants, which improves air quality, protects public health and slows climate change,” says study co-author Ananya Roy, senior health scientist at EDF. “It’s critical that the U.S. Environmental Protection Agency strengthen and finalize its proposed oil and gas methane rules as quickly as possible. These proposed rules should build from leading state approaches in Colorado and New Mexico and go further to end pollution from the practice of routine flaring.”
The authors say future studies should focus on learning more about health impacts across the full life cycle of O&G production, as well as the benefits of additional O&G pollution control strategies.
“There are technologies and strategies to reduce methane leaks, emissions from compressor stations, or emissions from other sources, such as ponds and dehydrators,” Buonocore says. “Each of these strategies will have different effects on the levels of different pollutants that get emitted.”
There is also more work to be done to quantify the health impacts of emissions that the study did not examine, such as benzene and formaldehyde, Arunachalam notes. “Exposure to these pollutants which have been detected near oil and gas wells can cause cancer and several other adverse health impacts, and quantifying them will demonstrate even higher public health benefits of controlling emissions from this sector.”

What cell types are found in which human tissue, and where? Which genes are active in the individual cells, and which proteins are found there? Answers to these questions and more are to be provided by a specialised atlas — in particular how the different tissues form during embryonic development and what causes diseases. In creating this atlas, researchers aim to map not only tissue directly isolated from humans, but also structures called organoids. These are three-dimensional clumps of tissue that are cultivated in the laboratory and develop in a way similar to human organs, but on a small scale.
“The advantage of organoids is that we can intervene in their development and test active substances on them, which allows us to learn more about healthy tissue as well as diseases,” explains Barbara Treutlein, Professor of Quantitative Developmental Biology at the Department of Biosystems Science and Engineering at ETH Zurich in Basel.
To help produce such an atlas, Treutlein, together with researchers from the Universities of Zurich and Basel, has now developed an approach to gather and compile a great deal of information about organoids and their development. The research team applied this approach to the organoids of the human retina, which they derived from stem cells.
Many proteins visible simultaneously
At the heart of the methods the scientists used for their approach was the 4i technology: iterative indirect immunofluorescence imaging. This new imaging technique can visualise several dozen proteins in a thin tissue section at high resolution using fluorescence microscopy. The 4i technology was developed a few years ago by Lucas Pelkmans, a professor at the University of Zurich and coauthor of the study that has just been published in the scientific journal Nature Biotechnology. It is in this study that the researchers applied this method to organoids for the first time.
Typically, researchers use fluorescence microscopy to highlight three proteins in a tissue, each with a different fluorescent dye. For technical reasons, it is not possible to stain more than five proteins at a time. In 4i technology, three dyes are used, but these are washed from the tissue sample after measurements have been taken, and three new proteins are stained. This step was performed 18 times, by a robot, and the process took a total of 18 days. Lastly, a computer merges the individual images into a single microscopy image on which 53 different proteins are visible. They provide information on the function of the individual cell types that make up the retina; for example, rods, cones, and ganglion cells.

The researchers have supplemented this visual information of retinal proteins with information on which genes are read in the individual cells.
High spatial and temporal resolution
The scientists performed all these analyses on organoids that were of different ages and thus at different stages of development. In this way, they were able to create a time series of images and genetic information that describes the entire 39-week development of retinal organoids. “We can use this time series to show how the organoid tissue slowly builds up, where which cell types proliferate and when, and where the synapses are located. The processes are comparable to those of retinal formation during embryonic development,” says Gray Camp, a professor at the University of Basel and a senior author of this study.
The researchers published their image information and more findings on retinal development on a publicly accessible website: EyeSee4is.
Further tissue types planned
So far, the scientists have been studying how a healthy retina develops, but in the future, they hope to deliberately disrupt development in retinal organoids with drugs or genetic modifications. “This will give us new insights into diseases such as retinitis pigmentosa, a hereditary condition that causes the retina’s light-sensitive receptors to gradually degenerate and ultimately leads to blindness,” Camp says. The researchers want to find out when this process begins and how it can be stopped.
Treutlein and her colleagues are also working on applying the new detailed mapping approach to other tissue types, such as different sections of the human brain and to various tumour tissues. Step by step, this will create an atlas that provides information on the development of human organoids and tissues.

After a stroke, physical activity can be pivotal to successful recovery. People who spend four hours a week exercising after their stroke achieve better functional recovery within six months than those who do not, a University of Gothenburg study shows.
The study, now published in the scientific journal JAMA Network Open, is based on data concerning 1,500 stroke patients in 35 Swedish hospitals. The participants were grouped according to their poststroke patterns of physical activity.
The results show that increased or maintained physical activity, with four hours’ exercise weekly, doubled the patients’ chances of recovering well by six months after a stroke. Men and people with normal cognition kept up an active life relatively more often, with better recovery as a result.
Positive programming from exercise
The researchers have previously succeeded in demonstrating a clear inverse association between physical activity and the severity of stroke symptoms at the actual onset of the condition. These new findings highlight the importance of maintaining a healthy, active lifestyle after a stroke.
The first and corresponding author of the study, Dongni Buvarp, is a researcher in clinical neuroscience at Sahlgrenska Academy, University of Gothenburg. Besides her research internship, she is a resident doctor at an initial stage of specialist training at Sahlgrenska University Hospital.
“Physical activity reprograms both the brain and the body favorably after a stroke. Exercise improves the body’s recovery at the cellular level, boosts muscle strength and well-being, and reduces the risk of falls, depression, and cardiovascular disease. Regardless of how severe the stroke has been, those affected can derive benefits from exercising more,” she says.
Knowledge and support vital
“Being physically active is hugely important, especially after a stroke. That’s a message that health professionals, stroke victims and their loved ones should all know. Women and people with impaired cognition seem to become less active after stroke. The study results indicate that these groups need more support to get going with physical activity,” Buvarp says.
One weakness of the study is that, with a few exceptions, the researchers were unable to study the participants’ degree of activity before the stroke. The patients included were treated in Sweden in the period from 2014 to 2019.

Depression due to psychological stress affects millions of people worldwide. However, most of the existing anti-depressant drugs are slow, prone to development of resistance, and have severe side effects, demanding the need for more effective treatment options.
Delta opioid receptors (DOPs) are known to play a key role in the development of depression and similar diseases. Previous studies have revealed that DOP agonists (substances that bind DOPs instead of the regular compound and cause the same effect) have improved efficacy and lower side effects than most existing anti-depressant drugs. Recent studies have identified KNT-127 as a potent DOP agonist with significant anti-depressant activity, quick action, and minimal side effects. However, the underlying mechanism of action is not well understood.
To this end, Prof. Akiyoshi Saitoh, Mr. Toshinori Yoshioka, Jr. Associate Prof. Daisuke Yamada, and Prof. Eri Segi-Nishida, at the Tokyo University of Science, along with Prof.Hiroshi Nagase from the University of Tsukuba, set out to assess the therapeutic and preventive effects of KNT-127 in a mouse model with depression. The findings of this study were made available online on 30 March, 2023, and published in the journal Neuropharmacology on 4 April, 2023.
Explaining the motivation behind their study, Prof. Saitoh explains, “We previously discovered that delta-opioid receptor (DOP) agonists may quick action and have a low risk of side effects compared to existing drugs. Thus, we have been working on their clinical development as a new treatment strategy for depression. In this study, we attempted to elucidate the mechanism of antidepressant-like effects of KNT-127, a selective DOP agonist, in a mouse model of depression.”
The hypothalamic-pituitary-adrenal axis, hippocampal neurogenesis, and neuroinflammation are regarded as the major factors in the processes leading to the development of depression. Thus, understanding the effect of KNT-127 on the above parameters was crucial towards decoding its underlying working principle.
To this end, Prof. Saitoh and team created the depression mouse model called chronic vicarious social defeat stress (cVSDS) mice, by exposing five-week-old male mice to extreme psychological stress for 10 minutes per day, repeated for 10 days. Next, KNT-127 was given to the mice both during (10 days) and after (28 days later) the stress period, to assess its efficacy.
They observed that prolonged administration of KNT-127 during (anti-stress effect) and after stress (anti-depressant effect) period, significantly improved social interaction and levels of serum corticosterone (a hormone secreted under stress in mice) in cVSDS mice. Moreover, KNT-127 administration during stress, suppressed stress-induced newborn neuronal death in the hippocampus, rather than increasing neurogenesis, or the formation of new neurons. In contrast, when administered after stress, KNT-127 did not affect newborn neuron survival rate at all. Furthermore, unlike conventional antidepressants, KNT-127 did not affect neurogenesis even under stress-free conditions.
Psychological stress increases the number of microglia and activated microglia in the brains of cVSDS mice. Interestingly, under both models of delivery, KNT-127 suppressed microglial activation and hence reduced inflammation in the hippocampus.
In a nutshell, during and post stress period, KNT-127 prevents neuronal inflammation and reduces newborn neuronal death without affecting neuron formation to exert anti-stress and anti-depressant-like effects, respectively. However, further research is warranted for better insights regarding DOP agonists and the mechanism underlying their anti-depressant effects.
The anti-stress effect of KNT-127 may offer added benefits for patients during treatment. Prof. Saitoh elaborates, “Patients with depression often have to face situations where they cannot avoid stressful environments, even during treatment. Therefore, we believe that the additional anti-stress effect during the treatment period has important clinical significance.”
Prof. Saitoh concludes by sharing their vision for the future, “We expect that the successful clinical development of DOP agonists will greatly broaden the options for the treatment of depression in the future.”