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Published13 hours agoShareclose panelShare pageCopy linkAbout sharingBy Catherine Burns and Vicki LoaderBBC Health TeamThe system for allocating most liver transplants on the NHS is causing younger patients to wait longer for surgery, figures show. There is a shortage of liver donors, so a computer algorithm decides who to prioritise on the waiting list.Younger people are currently waiting 156 days longer on average for a transplant than patients over 60.But NHS Blood and Transplant (NHS BT) says difficult decisions have to be made and the system is saving lives. Listen to BBC’s 5 Minutes On: Bottom of the Donor List – “My life’s on hold”There are about 700 people on the liver transplant waiting list in the UK – although that number fluctuates as new patients are added and some have their surgery.Others do not receive a transplant in time, with 69 people dying last year before they could get a liver.In 2018, a new computer algorithm was launched to cut deaths on the waiting list. It prioritises patients who are most likely to die soon, which in practice, tends to be older people. It does that by looking at 21 recipient parameters, such as age, disease type and severity, and seven donor ones.Then it gives a score. The higher the score, the more likely you are to get a liver soon.Younger patients have always had longer waits for liver transplants.Before the algorithm came in, 26 to 39-year-olds would expect to be on the list for an average of 172 days – which was about 40 days longer than for patients over 60. Now the gap has widened to 156 days. ‘Really quite dark’Sarah Meredith has not put her phone on silent since she went on the transplant list in July 2021 and has spent those two years waiting for the call telling her she has been matched to a donor liver.She has even moved from Devon to Cambridge so she can get to the hospital as soon as possible. But the call has never come. The 31-year-old needs a new liver because of a rare complication caused by cystic fibrosis. Sarah gets emotional as she describes being in pain every single day. “What concerns me the most is having my family watch me slowly die,” she told BBC News.At the same time, she is trying to cope with the mental strain of waiting for so long, saying that “it’s incredibly hard to keep yourself going”. “Some days it’s really quite dark,” Sarah adds.Sarah thinks her age, and the fact that she has a rare combination of conditions, are working against her. ‘This is something they haven’t asked for’Liver transplant surgeon Prof Nigel Heaton says he struggles to support his younger patients when he believes they could be waiting for years. They tend to be born with liver disease or to have developed it early in life.He says: “It’s not something they’ve done through drinking, drugs, or lifestyle. This is something that they haven’t asked for. “I think it’s our duty to try and do the best we can for them, and to restore them to a normal life.”He explains: “They’re not going to die immediately, but you can see they’re deteriorating on the waiting lists. “This jeopardises their chances of a successful transplant. and some will die without getting successful transplantation.”Instead, he wants the system to be tweaked, so they have the same opportunity as other age groups.Difficult decisionsOlive McGowan, the chief nurse for NHS Blood and Transplant, acknowledges that it is incredibly stressful for young patients on the waiting list. She points out that difficult decisions have to be made because there there are not enough livers to go around.She says: “What we must do is prevent patients from dying on the liver transplant waiting list. So we maximise this very precious gift and transplant those who are most in need.”Krishna Menon, president of the British Transplantation Society, says the algorithm is constantly monitored and can be changed. But he says “any adjustment to favour one particular group will inevitably disadvantage another group”.All sides agree about one key fact – it would not be necessary to pick between different groups of patients if more people donated their livers. Ms McGowan says: “The most important thing is to make your organ donation decision on the Organ Donor Register. “That important step is vital to save somebody’s life.”How to become a donorShona McFadyen, 30, also has painful memories being on the waiting list for almost four years, and says it was “mentally battering”.Like Sarah, she feels that the current system is unfair.She says: “Young people deserve as much of a chance as older people. “Something’s not quite right with people like me waiting nearly four years for a transplant.”We met her training for a swimming race, powering up and down the pool. She wants to encourage more people to consider organ donation, saying: “It has essentially given me a second chance at life. “I’m going to do everything in my power to make my donor family proud. I want that donor to live on in me.” More on this storyLiver kept alive outside of body for three daysPublished31 May 2022Woman waits nearly two years for liver transplantPublished20 AprilWarm organ storage ‘offers real hope’Published16 January 2019Related Internet LinksNHS Blood and TransplantNHS organ donor registerThe BBC is not responsible for the content of external sites.

Scientists at City of Hope, one of the largest cancer research and treatment organizations in the United States, have identified how low levels of the TET2 gene fuel the rapid growth of acute myeloid leukemia in animal models. Cell Stem Cell recently published the study.
A team led by Jianjun Chen, Ph.D., the Simms/Mann Family Foundation Chair in Systems Biology at Beckman Research Institute of City of Hope, found that TET2 deficiency sets off a cascade of biochemical changes that enhance the bone marrow cancer’s ability to spread. These changes include: Driving the movement of malignant stem cells from the bloodstream to the bone marrow region where they originated. This home microenvironment, called a niche, protects the cells’ survival and ability to divide and self-replicate. Increasing the expression of a protein called TSPAN13 that signals leukemia stem cells to travel back to the bone marrow niche Leading to the buildup of a methylated form of the RNA base cytosine that enhances TSPAN13 messenger RNA’s stability, resulting in the increased expression of TSPAN13 protein Activating a signaling pathway called the TSPAN13/CXCR4 axis that increases malignant stem cells’ return (i.e., homing) to the bone marrow niche and self-replication, thereby leading to the rapid development of leukemia.By expanding understanding of the multiple ways that TET2 influences the development of acute myeloid leukemia, the discovery points to new potential therapeutic targets for treating the disease.
“This study provides novel insights into the cellular and molecular mechanisms underlying the development of acute myeloid leukemia,” Chen said. “Our findings highlight the therapeutic potential of reactivating TET2 signaling in patients with TET2 mutations or transcriptional suppression. Equally exciting, this strategy could be applied to other types of cancer that feature TET2 deficiency.”
Acute myeloid leukemia is distinguished by the rapid division and spread of immature leukemia stem cells. More than half of patients relapse, and the five-year survival rate is only 30%. Figuring out how to destroy these cells is crucial to effectively treating the disease.
TET2 deficiency cooperates with leukemia-related oncoproteins resulting from chromosomal abnormalities or gene mutations to drive the development of leukemia and enhance malignant stem cells’ ability to divide and spread. Until now, however, the cellular and molecular mechanisms underlying these processes have remained murky.
In analyzing data from the Cancer Genome Atlas, Chen and his colleagues found that lower expression or mutation of TET2 was associated with a poor prognosis and shorter overall survival rates for patients. Compared to healthy control subjects, TET2 expression was significantly suppressed in acute myeloid leukemia patients. This led the team to investigate the clinical relevance of TET2 in the development of the disease.
The research was partly supported by grants from the National Institutes of Health (R01 CA214965, R01 CA243386, R01 CA236399, R01 CA271497, R01 DK124116 and R01 CA280389), the Simms/Mann Family Foundation, Leukemia Research Foundation New Investigator Research Grant, The Margaret E. Early Medical Research Trust, and the American Association for the Study of Liver Diseases Foundation (PNC22-261362 and T32 CA186895).

Some women with early-stage, low-risk breast cancer may not need radiotherapy after breast conserving surgery according to new research led by McMaster University, BC Cancer, Hamilton Heath Sciences, and the University of British Columbia.
The research, published in The New England Journal of Medicine on Aug. 17, shows women 55 or older with a specific subtype of Stage 1 breast cancer can be effectively treated with just surgery and endocrine therapy.
The findings, which were initially presented in June 2022 at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, have since been peer-reviewed and are now being published in full detail.
Women with early breast cancer who have breast conserving surgery typically receive radiation to the breast daily for several weeks to reduce the risk of cancer returning in the breast. However, radiation can be costly, inconvenient for the patient and associated with both short-term side effects — such as tiredness and skin irritation — and long-term side effects — such as breast pain and thickening of the breast tissue, which can affect how the breast looks and a woman’s quality of life.
The subtype of breast cancer that researchers focused on — luminal A — represents up to 60 per cent of all breast cancers diagnosed annually and is associated with a lower risk of recurrence. With this new approach, a significant proportion of women can be spared of radiation after breast conserving surgery. Eliminating the need for this group to receive radiation will allow women to avoid the side effects of therapy and can add capacity back into the public health care system, permitting increased access for those who require radiation therapy more urgently.
“This is a major advance in our treatment approach for breast cancer. With a better understanding of the molecular biology of breast cancer we can now identify women who do not need radiation,” said Tim Whelan, lead author of the study, a professor in the Department of Oncology at McMaster University and the Canada Research Chair in Breast Cancer Research. Whelan is also a radiation oncologist at Hamilton Health Sciences.
The study was coordinated by the Ontario Clinical Oncology Group at Hamilton Heath Sciences, and followed 500 women from across Canada who were 55 years of age or older, had undergone breast conserving surgery, and their tumours were smaller than two centimetres without cancer in the lymph nodes under the arm. The growth rate of a woman’s tumour was assessed with a simple, low-cost and made-in-B.C. version of a molecular test called Ki67, which provided a quantitative measure that the participant’s cancer was low-risk. In the trial, the luminal A sub-type was determined by a low reading on the Ki67 test plus the tumour having both the estrogen and progesterone receptors. If determined to be low risk, women were enrolled in the trial where they received standard endocrine therapy but not radiation. Radiation therapy is standard practice, so participants were monitored through regular clinical exams and annual mammograms. When planning the study, the investigators predicted that the risk of developing recurrence in the breast would be very low at five years.

Pre-clinical trials by University of Queensland researchers have found an injection of a specific blood factor can replicate the benefits of exercise in the brain.
Dr Odette Leiter and Dr Tara Walker from UQ’s Queensland Brain Institute led a team which discovered platelets, the tiny blood cells critical for blood clotting, secrete a protein that rejuvenates neurons in aged mice in a similar way to physical exercise.
“We know exercise increases production of new neurons in the hippocampus, the part of the brain important for learning and memory, but the mechanism hasn’t been clear,” Dr Leiter said.
“Our previous research has shown platelets are involved, but this study shows platelets are actually required for this effect in the aged mice.”
The researchers focused on exerkines, the biological compounds released into the bloodstream during exercise, which are believed to stimulate the exercise-induced response in the brain.
“We discovered that the exerkine CXCL4/Platelet factor 4 or PF4, which is released from platelets after exercise, results in regenerative and cognitive improvements when injected into aged mice,” Dr Leiter said.
Dr Walker said the findings have significant implications for the development of drug interventions.

Osaka Metropolitan University scientists have developed an AI model that accurately estimates a patient’s age, using chest radiographs of healthy individuals collected from multiple facilities. Furthermore, they found a positive relationship between differences in the AI-estimated and chronological ages and a variety of chronic diseases, such as hypertension, hyperuricemia, and chronic obstructive pulmonary disease. In the future, it is expected that AI biomarkers will be developed to predict life expectancy, estimate the severity of chronic diseases, and forecast surgery-related risks.
What if “looking your age” refers not to your face, but to your chest? Osaka Metropolitan University scientists have developed an advanced artificial intelligence (AI) model that utilizes chest radiographs to accurately estimate a patient’s chronological age. More importantly, when there is a disparity, it can signal a correlation with chronic disease. These findings mark a leap in medical imaging, paving the way for improved early disease detection and intervention. The results are set to be published in The Lancet Healthy Longevity.
The research team, led by graduate student Yasuhito Mitsuyama and Dr. Daiju Ueda from the Department of Diagnostic and Interventional Radiology at the Graduate School of Medicine, Osaka Metropolitan University, first constructed a deep learning-based AI model to estimate age from chest radiographs of healthy individuals. They then applied the model to radiographs of patients with known diseases to analyze the relationship between AI-estimated age and each disease. Given that AI trained on a single dataset is prone to overfitting, the researchers collected data from multiple institutions.
For the development, training, internal and external testing of the AI model for age estimation, a total of 67,099 chest radiographs were obtained between 2008 and 2021 from 36,051 healthy individuals who underwent health check-ups at three facilities. The developed model showed a correlation coefficient of 0.95 between the AI-estimated age and chronological age. Generally, a correlation coefficient of 0.9 or higher is considered to be very strong.
To validate the usefulness of AI-estimated age using chest radiographs as a biomarker, an additional 34,197 chest radiographs were compiled from 34,197 patients with known diseases from two other institutions. The results revealed that the difference between AI-estimated age and the patient’s chronological age was positively correlated with a variety of chronic diseases, such as hypertension, hyperuricemia, and chronic obstructive pulmonary disease. In other words, the higher the AI-estimated age compared to the chronological age, the more likely individuals were to have these diseases.
“Chronological age is one of the most critical factors in medicine,” stated Mr. Mitsuyama. “Our results suggest that chest radiography-based apparent age may accurately reflect health conditions beyond chronological age. We aim to further develop this research and apply it to estimate the severity of chronic diseases, to predict life expectancy, and to forecast possible surgical complications.”

A single injection of a novel CRISPR gene-editing treatment safely and efficiently removes SIV — a virus related to the AIDS-causing agent HIV — from the genomes of non-human primates, scientists at the Lewis Katz School of Medicine at Temple University now report. The groundbreaking work complements previous experiments as the basis for the first-ever clinical trial of an HIV gene-editing technology in human patients, which was authorized by the Food and Drug Administration (FDA) in 2022.
The preclinical study, published online in the journal Gene Therapy, tested EBT-001, an SIV-specific CRISPR-Cas9 gene-editing therapy, in rhesus macaques. The study shows that EBT-001 effectively excises SIV from reservoirs — cells and tissues where viruses like SIV and HIV integrate into host DNA and hide for years — without any detectable off-target effects in animals. The work is a significant advance in the generation of a cure for HIV/AIDS in humans.
“Our study supports safety and demonstrates evidence of in vivo SIV editing of a CRISPR gene-editing technology aimed at the permanent inactivation of virus in a broad range of tissues in a large, preclinical animal model, using a one-time injection of the treatment,” said Kamel Khalili, PhD, Laura H. Carnell Professor and Chair of the Department of Microbiology, Immunology, and Inflammation, Director of the Center for Neurovirology and Gene Editing, Director of the Comprehensive NeuroAIDS Center at the Lewis Katz School of Medicine, and senior investigator on the new study.
“The outcome of the preclinical model set the stage for the ongoing clinical trial of EBT-101, which is sponsored and managed by Excision Biotherapeutics, Inc.,” he explained.
EBT-101 is a unique gene-editing treatment that has the potential to shape the future of HIV therapeutics. Its development is the result of a collaborative effort between researchers at the Lewis Katz School of Medicine and scientists at Excision BioTherapeutics, Inc.
Before clinical trials of EBT-101 could be undertaken in humans, the researchers first collected data on safety from studies in non-human primates. This necessitated the use of a version of EBT-101 adapted to treat SIV infection, which mimics HIV infection in humans but is specific to non-human primates. For the preclinical trial, Dr. Khalili and colleagues packaged the SIV-specific CRISPR-Cas9 gene-editing construct, called EBT-001, into an adeno-associated virus 9 (AAV9) carrier, which could be injected intravenously into SIV-infected animals.
Tricia H. Burdo, PhD, Professor and Vice Chair in the Department of Microbiology, Immunology, and Inflammation and the Center for Neurovirology and Gene Editing at the Lewis Katz School of Medicine and an expert in non-human primate HIV-1 models, led the animal studies. Her team randomized 10 animals into control and treatment groups, with three animals left untreated and the remainder receiving a single injection of EBT-001 at one of three different dose levels. Two additional animals were utilized in a separate study using a higher dose. Necropsy and tissue analyses were carried out at three or six months after the start of treatment. Data was collected on biodistribution, which involved histopathological investigation of sites of viral latency, including lymph node and spleen tissue, as well as other tissues, and on safety, which included off-target analyses at the different dose levels.

Reasoning skills are crucial skills in learning, academic performance, and everyday problem-solving. According to a recent study conducted at the University of Eastern Finland, improved overall diet quality and reduced consumption of red meat, as well as increased time spent in reading and organised sports enhanced reasoning skills among children over the first two school years.
“Children with healthier eating habits showed greater cognitive development than other children. Specifically, better overall diet quality, lower red meat consumption, and higher low-fat dairy product intake were linked to better reasoning skills,” says Doctoral Researcher Sehrish Naveed of the University of Eastern Finland.
Children who spent more time in reading and organised sports showed better reasoning skills than their peers. On the other hand, excessive time spent on a computer and unsupervised leisure-time physical activity were associated with poorer reasoning skills. Screen time, active school transportation, recess physical activity, and physical activity intensity were not associated with reasoning skills.
Over half of the children participated in a two-year family-based and individualised diet and physical activity intervention. However, the intervention did not impact reasoning skills, with the children in the intervention and control groups exhibiting similar cognitive development.
“In the lives of growing children, diet and physical activity intervention is just one factor influencing lifestyle and reasoning skills. Based on our study, investing in a healthy diet and encouraging children to read are beneficial for the development of reasoning skills among children. Additionally, engaging in organised sports appears to support reasoning skills,” Dr Eero Haapala points out.
Published in the  Scandinavian Journal of Medicine & Science in Sports, the results of this study are based on data from the Physical Activity and Nutrition in Children (PANIC) study. This sub-study examined the effects of a two-year diet and physical activity intervention on cognition among 397 Finnish elementary school children. The associations of dietary factors, physical activity, and sedentary behaviour with cognition over two years were also studied. The analyses considered parental education and income as well as children’s body fat percentage and maturity level.

A new study from Lund University in Sweden raises questions about the efficacy of bariatric operations involving gastric bypass. The results show that the biggest metabolic changes happened directly after surgery. Just a year after the operation, the concentration of metabolites and fats had returned to almost the same levels as before the procedure.
Previous research has shown that the majority of those who undergo surgery regain weight within five years of a gastric bypass operation. It has still not been established what happens to the metabolism of those who have had a bariatric procedure. In a new study published in the journal Obesity, the researchers studied the metabolism of overweight individuals before and after they had a gastric bypass operation. The study shows that the biggest changes happened straight after the procedure. One year later, the concentration of metabolites and fats among all the participants were nearing the same levels as before the operation.
“Just following up on the weight of people can be a blunt instrument for studying the effects of the procedure. Our study provides a greater understanding of what happens to the metabolism in connection with a gastric bypass operation,” says Peter Spégel, associate professor of molecular metabolism at Lund University, who led the study.
Rapid changes
The study was based on data from 148 people with and without type 2 diabetes who underwent a gastric bypass operation in Sweden. Blood samples were collected from participants just before the procedure and on at least two occasions after the operation. Their body mass index (BMI) was measured before the operation and on three occasions afterwards.
The researchers conducted detailed analyses of fats and metabolites in the blood. Just one year after the operation, some of the participants were back at exactly the same levels as before the surgery, whereas the reversion was not as marked for others.
“We could see the changes while the participants still had a low BMI after the operation. By studying metabolism, we can obtain a clear indication that unhealthy changes are on the way. We hope that the knowledge can be used in follow-up so that preventive measures can be put in place,” says Nils Wierup, professor of neuroendocrine cell biology at Lund University and one of the main authors of the article.

New animal research suggests that little-studied brain cells known as astrocytes are major players in controlling sleep need and may someday help humans go without sleep for longer without negative consequences such as mental fatigue and impaired physical health.
Published in the Journal of Neuroscience, the study found that activating these cells kept mice awake for hours when they would normally be resting, without making them any sleepier.
“Extended wakefulness normally increases sleep time and intensity, but what we saw in this study was that despite hours of added wakefulness these mice did not differ from well-rested controls in terms of how long and how intensely they slept,” said senior author Marcos Frank, a neuroscientist and professor at the Washington State University Elson S. Floyd College of Medicine. “This opens up the possibility that we might someday have interventions that could target astrocytes to mitigate the negative consequences of prolonged wakefulness.”
Frank envisioned that might include medications that could be used to improve the productivity, safety and health of shift workers and others who work long or odd hours, such as first responders and military personnel. Sleep loss and mistimed sleep have been shown to impact a variety of key processes, including attention, cognition, learning, memory, metabolism and immune function.
Astrocytes are types of non-neuronal cells that interact with neurons, brain cells that transmit easily measured electrical signals from the brain to other parts of the body. Previously thought of as merely the “glue” that holds the brain together, astrocytes have recently been shown to play an active role in various behaviors and processes through a much more subtle and difficult-to-measure process known as calcium signaling. This includes a previous WSU study that showed that suppressing astrocyte calcium signaling throughout the brain resulted in mice building up less sleep need after sleep deprivation.
In this study, the researchers looked specifically at astrocytes in the basal forebrain, a brain region known to play a critical role in determining time spent asleep and awake as well as sleep need. Using chemogenetics — a method to control and study signaling pathways within brain cells — they activated these astrocytes and found that this resulted in mice staying awake for 6 hours or more during their normal sleep period. What’s more, the researchers did not see subsequent changes in sleep time or sleep intensity in response to the added wakefulness, as would be expected.
“Our findings suggest that our need for sleep isn’t just a function of prior wake time but is also driven by these long-ignored non-neuronal cells,” said first author Ashley Ingiosi, an assistant professor of neuroscience at Ohio State University who conducted the study while working as a postdoctoral research associate in Frank’s lab at WSU. “We can now start to pinpoint how astrocytes interact with neurons to trigger this response and how they drive the expression and regulation of sleep in different parts of the brain.”
Next, the researchers plan to conduct behavioral tests in mice to determine how activating basal forebrain astrocytes to induce wakefulness might impact other processes besides sleep need, such as attention, cognition, learning, memory, metabolism and immune function. To get at least some indication of the potential impact on attention and cognition, they looked at EEG markers of those two processes in this study and found them to be similar to those seen in well-rested controls.
Funding support for the study came from the National Institutes of Health.

Neuroscientists today report the first results from experimental tests designed to explore the idea that “forgetting” might not be a bad thing, and that it may represent a form of learning — and outline results that support their core idea.
Last year the neuroscientists behind the new theory suggested that changes in our ability to access specific memories are based on environmental feedback and predictability. And that rather than being a bug, forgetting may be a functional feature of the brain, allowing it to interact dynamically with a dynamic environment.
In a changing world like the one we and many other organisms live in, forgetting some memories would be beneficial, they reasoned, as this can lead to more flexible behaviour and better decision-making. If memories were gained in circumstances that are not wholly relevant to the current environment, forgetting them could be a positive change that improves our wellbeing.
Today, in the journal Cell Reports, they present the first in a series of new experimental studies where the effect of natural, “every day” forgetting was investigated with respect to how normal forgetting processes affect particular memories in the brain.
The team studied a form of forgetting called retroactive interference, where different experiences occurring closely in time can cause the forgetting of recently formed memories. In their study, mice were asked to associate a specific object with a particular context or room, and then recognise that an object that was displaced from its original context. However, mice forget these associations when competing experiences are allowed to ‘interfere’ with the first memory.
To study the result of this form of forgetting on memory itself, the neuroscientists genetically labelled a contextual “engram” (a group of brain cells that store a specific memory) in the brains of these mice, and followed the activation and functioning of these cells after forgetting had happened. Crucially, using a technique called optogenetics they found that stimulation of the engram cells with light retrieved the apparently lost memories in more than one behavioural situation. Furthermore, when the mice were given new experiences that related to the forgotten memories, the ‘lost’ engrams could be naturally rejuvenated.
Dr Tomás Ryan, Associate Professor in the School of Biochemistry and Immunology and the Trinity College Institute of Neuroscience at Trinity College Dublin, is lead author of the just-published journal article.