Publisher Health

Mammals can’t typically regenerate organs as efficiently as other vertebrates, such as fish and lizards. Now, Salk scientists have found a way to partially reset liver cells to more youthful states — allowing them to heal damaged tissue at a faster rate than previously observed. The results, published in Cell Reports onApril 26, 2022, reveal that the use of reprogramming molecules can improve cell growth, leading to better liver tissue regeneration in mice.
“We are excited to make strides at repairing cells of damaged livers because, someday, approaches like this could be extended to replacing the whole organ itself,” says corresponding author Juan Carlos Izpisua Belmonte, a professor in Salk’s Gene Expression Laboratory and holder of the Roger Guillemin Chair. “Our findings could lead to the development of new therapies for infection, cancer and genetic liver diseases as well as metabolic diseases like nonalcoholic steatohepatitis (NASH).”
The authors previously showed how four cellular reprogramming molecules — Oct-3/4, Sox2, Klf4 and c-Myc, also called “Yamanaka factors” — can slow down the aging process as well as improve muscle tissue regeneration capacity in mice. In their latest study, the authors used Yamanaka factors to see if they could increase liver size and improve liver function while extending the health span of the mice. The process involves partially converting mature liver cells back to “younger” states, which promotes cell growth.
“Unlike most of our other organs, the liver is more effective at repairing damaged tissue,” says co-first author Mako Yamamoto, a staff researcher in the Izpisua Belmonte lab. “To find out if mammalian tissue regeneration could be enhanced, we tested the efficacy of Yamanaka factors in a mouse liver model.”
The issue many researchers in the field face is how to control the expression of factors needed for improving cell function and rejuvenation as some of these molecules can cause rampant cell growth, such as occurs in cancer. To circumvent this, Izpisua Belmonte’s team used a short-term Yamanaka factor protocol, where the mice had their treatment administered for only one day. The team then tracked the activity of the partially reprogrammed liver cells by taking periodic samples and closely monitoring how cells divided over several generations. Even after nine months — roughly a third of the animal’s life span — none of the mice had tumors.
“Yamanaka factors are truly a double-edged sword,” says co-first author Tomoaki Hishida, a former postdoctoral fellow in the Izpisua Belmonte lab and current associate professor at Wakayama Medical University in Japan. “On the one hand, they have the potential to enhance liver regeneration in damaged tissue, but the downside is that they can cause tumors. We were excited to find that our short-term induction protocol has the good effects without the bad — improved regeneration and no cancer.”
The scientists made a second discovery while studying this reprogramming mechanism in a lab dish: A gene called Top2a is involved in liver cell reprogramming and is highly active one day after short-term Yamanaka factor treatment. Top2a encodes Topoisomerase 2a, an enzyme that helps break up and rejoin DNA strands. When the researchers blocked the gene, which lowered Topoisomerase 2a levels, they saw a 40-fold reduction in cellular reprogramming rates, leading to far fewer young cells. The exact role that Top2a plays in this process remains a future area of research.
“There is still much work to be done before we can fully understand the molecular basis underlying cellular rejuvenation programming approaches,” says Izpisua Belmonte. “This is a necessary requirement for developing effective and universal medical treatments and reversing the effects of human disease.”
Izpisua Belmonte is currently Institute Director of Altos Labs Inc., in addition to being a professor at the Salk Institute.
This work was supported by a Uehara Memorial Foundation research fellowship UCAM and Fundacion Dr. Pedro Guillen.
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Viruses are among the most protean entities in nature, ceaselessly mutating and acquiring new characteristics. These tiny entities follow a simple and relentless imperative: infect as many host organisms as possible. Occasionally, a virus’ genomic alterations enable it to leap from one species to another, in a process known as spillover.
In new research appearing in the journal mBio, Masmudur Rahman and his Arizona State University colleagues join international researchers to investigate one such spillover event, when the myxoma virus (MYXV) made a species leap from European rabbits to Iberian hares.
The study describes M159, a virus protein called a “host range factor” that arose very recently through a fortuitous gene pickup in the myxoma virus. The resultant hybrid strain, known as MYXV-Tol, has enabled the virus to expand its existing host range, traversing the species barrier and causing lethal disease in Iberian hares.
Researchers would like to better understand these genomic transitions, as spillover events have profound implications for both human and animal health. One such recent event, caused by mutations in a novel, SARS-like virus of unknown origin, is responsible for the global pandemic of COVID-19 disease, which has killed over five million people globally.
Understanding the subtle alterations enabling viruses to make species jumps may help better prepare for outbreaks of new diseases, limit their transmission, and perhaps allow researchers to outwit viral mechanisms that set the stage for spillover events. Human-engineered therapies against pathogens (including viruses) are part of a never-ending arms race between infectious agents and their host organisms.
In addition to its importance for the study of host- pathogen coevolution, myxoma virus has been investigated for its remarkable ability to target and kill human cancer cells, while leaving their normal healthy cell counterparts unharmed. It is one of the most promising viruses available in the new field of virotherapy, which uses cancer fighting or oncolytic viruses, including myxoma.

A potential game-changer in the tuberculosis epidemic was how the tuberculosis community viewed rapid molecular tests for tuberculosis and tuberculosis drug resistance. This was 12 years ago, with the launch of Xpert MTB/RIF, which gives results in less than two hours, simultaneously diagnosing tuberculosis and testing if the bacteria have rifampicin resistance, a type of drug-resistant tuberculosis. Multidrug-resistant tuberculosis is caused by resistance to at least both rifampicin and isoniazid, the two most effective first-line drugs used to treat tuberculosis.
Yet, diagnostic tests only have an impact on health if they are put to use in a correct and timely manner. To ensure diagnostics are accessible and utilized, we need to understand the views of recipients and providers who have used these tests, and a new qualitative evidence synthesis review published by the Cochrane Infectious Diseases Group (CIDG) pulls together all relevant research to date on Xpert MTB/RIF and similar tests. The authors also wanted to understand the implications of the review findings on effective implementation and health equity.
Rapid molecular tests have been shown to be accurate in diagnosing tuberculosis and rifampicin resistance and are recommended by the World Health Organization as the initial test in people with presumptive tuberculosis, replacing sputum microscopy, a test from the 19th century. These tests have many benefits, including the fact that they do not require well-equipped laboratories and skilled personnel, and can be carried out in community health settings, nearer to where people live. This is particularly relevant in low- and middle-income countries, settings with a high burden of tuberculosis.
Examining the evidence from 32 included studies, the review author team identified aspects of these tests that users valued most and challenges to realizing those values. People with tuberculosis valued an accurate diagnosis (knowing what is wrong with me), avoiding delays, and keeping diagnostic-associated cost low. Similarly, healthcare providers valued test accuracy and confidence in results (which helps in starting treatment), rapid results, and keeping cost to people seeking a diagnosis low. In addition, providers valued diversity of sample types (for example, gastric aspirate specimens and stool in children) and ability to detect drug resistance early. Laboratory professionals appreciated the improved ease of use compared to microscopy and increased staff satisfaction.
Reported challenges included reluctance to test for tuberculosis owing to stigma or cost concerns; health system inefficiencies such as poor quality of specimens, difficulty in transporting specimens, lack of sufficient staff or equipment, increased workload for providers, inefficiencies in integrating the test into clinic routines and clinicians relying too much on the test result at expense of their own experience with diagnosing tuberculosis; as well as implementation processes hampered by insufficient data about real-life situations, lack of inclusion of all relevant stakeholders (local decision-makers, providers or people seeking a diagnosis), and conflicts of interest between donors and people implementing the tests.
“The findings reveal a fundamental paradox between supporting technological innovations but not in parallel investing in health system infrastructure strengthening. The view that these low-complexity diagnostics are a solution to overcome deficiencies in laboratory infrastructure and lack of skilled professional is misleading. Implementation of new diagnostic technologies, like those considered in this review, will need to tackle the challenges identified in this review including weak infrastructure and systems, and insufficient data on ground level realities prior and during implementation, as well as problems of conflicts of interest in order to ensure quality care and equitable use of resources.” stated Nora Engel, lead author of the review.
The review authors called for future research to examine the implications of repurposing diagnostic infrastructure and equipment for COVID-19 and the issue of competition for diagnostic resources more generally.
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Oh my aching back.
It’s a common complaint, and one that health officials say causes more disability around the world than any other condition.
A new device, however, the exosuit, shows promise in assisting with back and shoulder injury prevention. Still, not one of the devices manufactured to date is “just right” says Vesna Novak, PhD, an electrical engineering and computer science professor at the University of Cincinnati.
Novak’s research team studies exosuits, a wearable mobile machine that allows for limb movement with increased strength and endurance.
“Nothing has been perfected so we are trying to figure out what works and what doesn’t so we can zero in,” Novak says of the team’s latest research published in the journal Applied Ergonomics. The demand for exosuits is highest among industries where employees do a lot of heavy, repetitive lifting such as in warehouse work, construction work and the airline industry. Exosuits are a less expensive, less cumbersome version of an exoskeleton, which is primarily used in the medical field.
“Back support exosuits can support workers in physically demanding jobs by reducing muscle load, which could reduce risk of work-related musculoskeletal disorders,” she says.
For this study, funded by the National Science Foundation, Novak says they looked at the commercially available Auxivo LiftSuit 1.1 and found both pros and cons.
“Its main weakness is that it’s kind of rigid and uncomfortable, so it’s good for short-term but not medium-term wear,” says the study’s lead author Maja Gorsic, a postdoctoral researcher under Novak’s tutelage.
Although study participants found the tasks mildly to moderately easier to perform with the exosuit than without it, “the LiftSuit does not appear to be flexible enough: as it is very stiff around the low back and hips, squatting motions are uncomfortable for wearers,” says Gorsic.
Thus, Novak says, wearers are more likely to lift with their back, leaning their hips back into the exosuit which defeats the purpose. The team compared/contrasted this device with their prior study of the HeroWear Apex suit, which did not appear to have these same issues, but was lacking in other areas.
“Both of the suits had limitations and the Auxivo LiftSuit manufacturer is already making an improved suit based on our feedback,” says Novak.
Calling on academic researchers to do the heavy lifting where exosuit testing is concerned is common practice, says Novak.
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Genetic risk factors and diet quality are independently associated with type 2 diabetes; a healthy diet is linked to lower diabetes risk across all levels of genetic risk. That’s the conclusion of a study of more than 35,000 US adults publishing April 26 in PLOS Medicine by Jordi Merino of Massachusetts General Hospital, US, and colleagues.
Both genetic and lifestyle factors are known to contribute to individual susceptibility to type 2 diabetes. Previous studies have shown that adherence to a healthy lifestyle is associated with reduced risk of type 2 diabetes across genetic profiles, but whether genetic profiles, in part, interact with lifestyle factors was unclear. In the new study, researchers analyzed data from three extensive cohort studies, including 35,759 U.S. health professionals followed for 902,386 person-years of follow-up.
The team found that, irrespective of genetic risk, a low diet quality, as compared to high diet quality, was associated with a 30% increased risk of type 2 diabetes (Pinteraction=0.69). The relative risk of type 2 diabetes was 1.29 (95% CI 1.25-1.32, P

Globally, the prevalence of type 2 diabetes mellitus (T2DM) is increasing. A study publishing April 26 in the open access journal PLOS Medicine by Marisa Miraldo at Imperial College Business School, London, United Kingdom, and colleagues suggests that living near fast food restaurants increases the risk of developing Type 2 diabetes.
Food environments have an impact on diet and obesity-two risk factors for T2DM. However, the relationship between food environments and diet in low- and middle-income countries is poorly understood. To examine the associations between the density and proximity of healthy and unhealthy food outlets and diabetes, researchers linked cross-sectional health data with environment mapping surveys for 12,167 people living in Bangladesh and Sri Lanka from 2018-2020. They collected self-reported diabetes diagnosis histories and fasting blood glucose levels from residents of urban and rural districts. The researchers then mapped the food environment, collecting data on location and types of food retailer available within 300 meters of each participant’s home, categorizing each type of food outlet as healthy or unhealthy.
The researchers found that a higher density of fast food outlets near an individual’s home was associated with an 8% increase in their probability of a diabetes diagnosis. Having at least one fast food retailer in the proximity of one’s home was associated with 2.14 mg/dL blood glucose increase. Additionally, women and high-income earners were more likely to have higher diabetes mellitus levels. The study was limited by several factors, including the self-reported data on diabetes diagnoses. The study also did not account for the actual diets of participants, which may have been sourced far from their homes, and may be confounded by other variables associated with diabetes. Future studies are needed to validate and expand on how food environments may impact individuals’ diets and health.
According to the authors, “Our results show interventions targeting the environment may be effective in preventing diabetes, however, the heterogeneity of the effects found in our analysis suggests that more specific interventions may be needed. One-size-fits-all built environment interventions have not led to improved outcomes and future research is needed to evaluate which food environment interventions could improve diabetes outcomes in this geographical region and population.”
“In South Asia diabetes affects 1 in 11 adults and causes 747,000 preventable deaths per year,” Miraldo adds. “Our research shows living in proximity to at least one fast food outlet is associated with a 16% increase in the chance of being diagnosed with diabetes. With the number of people with diabetes in Southeast Asia projected to reach 113 million by 2030, it is imperative food and beverage companies and retailers step up their sustainability agendas to promote better diets and prevent diabetes.”
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Cognitive development in children could be affected regardless of which biological parent has type 1 diabetes, according to research publishing April 19 in the open access journal PLOS Medicine. The research shows for the first time that having a parent with a chronic disease like type 1 diabetes may be associated with lower school performance rather than maternal high blood sugar during fetal development.
The influence of maternal diabetes during pregnancy on the cognition of their children has been widely researched. Glucose crosses the placenta and maternal high blood sugar, hyperglycemia, can affect fetal development including the baby’s brain. There is little evidence on different diabetes subtypes and the effect of having a father with type 1 diabetes.
Anne Lærke Spangmose and colleagues from Copenhagen University Hospital, Denmark obtained data from Danish registers and also on test scores in math for grades three and six, and reading for grades two, four, six and eight. The team included 622,073 children between 6-18 years old attending public schools over a seven-year period. There were 2,144 children with mothers with type 1 diabetes, 3,474 children with fathers with type 1 diabetes, and 616,455 children from the background population. Children of mothers and fathers with type 1 diabetes had mean scores of 54.2 and 54.4 respectively, compared with mean scores of 56.4 in children from the background population.
The team acknowledge that having a parent suffering from a serious chronic disease like diabetes could cause stress and be detrimental to a child’s school performance. However this study suggests a different explanation for previously observed adverse effects of maternal type 1 diabetes during pregnancy on children’s cognitive development.
Spangmose adds, “Lower test scores in the offspring of mothers with type 1 diabetes appear to reflect a negative association of having a parent with type 1 diabetes rather than a specific adverse effect of maternal type 1 diabetes during pregnancy on the fetus. Our recent large Danish cohort study, including 622,073 children, has shown this.”
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Shielding those vulnerable to COVID-19, while allowing the virus to spread, largely unmitigated, through the rest of the population, would have failed according to a new modelling paper published today in PLOS Global Public Health by University of Bath scientists.
Shielding strategies or “focused protection,” as advocated for in the Great Barrington Declaration, would have been impossible to implement in practice and would have likely led to far worse outcomes. Even if implemented perfectly, the modelling reveals that allowing the infection to spread through less vulnerable groups prior to vaccination would have overwhelmed health care capacity in the UK and led to tens of thousands of unnecessary deaths. In reality, practical considerations would have meant that large numbers of vulnerable people who were supposed to be protected would also have died.
The unprecedented scale of the public health crisis posed by the COVID-19 pandemic forced governments around the world to impose restrictions on social contact to suppress transmission of the coronavirus. However, the social and economic costs of these measures, especially lockdowns, have been high, drawing substantial opposition from some sections of the media, members of the public, and a small, but vocal group of scientists.
An alternative and widely discussed strategy would have been to temporarily focus protection on (“shield”) those who were most vulnerable to COVID-19 (the elderly and those with certain pre-existing conditions), with the aim of achieving herd immunity by allowing a largely unmitigated epidemic in the rest of the population. However, this approach has received little scrutiny in the form of mathematical modelling.
In this new study, published today, the researchers assessed a hypothetical large city in England with a population of 1 million inhabitants, using an SEIR (Susceptible, Exposed, Infected, Removed) model. They compared the outcomes from no shielding, with imperfect and perfect shielding, with shielding restrictions lifted when cases fall below a given threshold.
The research concludes that while shielding may have protected the vulnerable in theory, it required extremely restrictive conditions that were impossible to achieve in practice. For example, because shielding in real populations would have been imperfect, infections in the lower-risk population would have leaked through to vulnerable people who were shielding. In addition, if lower-risk individuals reduced social contact to avoid infection it may have been impossible to achieve herd immunity, meaning a second wave of infections would have occurred after shielding had ended. Even if herd immunity was achieved, care homes would still have been at risk of local outbreaks because immunity would have been unevenly distributed in the population.

The common perception that nearly everyone in America seemed to have been infected with the Omicron variant last winter may not have been far from the truth. By February 2022, nearly 60 percent of the population had been exposed to the coronavirus, almost double the proportion seen in December 2021, according to data released on Tuesday by the Centers for Disease Control and Prevention.“By February 2022, evidence of previous Covid-19 infections substantially increased among every age group,” Dr. Kristie Clarke, the agency researcher who led the study, said at a news briefing.Infections rose most sharply during the Omicron surge among children and adolescents, perhaps because many people in those age groups were still unvaccinated. The increase was smallest among adults 65 or older, who have the highest rate of vaccination and may be the most likely to take precautions.The new research suggests that three out of four children and adolescents in the United States had been exposed to the coronavirus by February 2022, compared with one-third of older adults.While some studies suggest that prior infection offers a weaker shield against the virus than vaccines do, exposure to the virus should provide a reasonable degree of protection against severe illness, at least in the short term.“We still do not know how long infection-induced immunity will last,” Dr. Clarke said.The gains in population-wide immunity nationwide may explain why the new surge that is roaring through China and many countries in Europe has been muted in the United States so far.The findings may offer some comfort to parents who have been waiting anxiously for a vaccine to be approved for the youngest children. Many of those children now seem to have acquired at least some immunity.Even so, Dr. Clarke urged parents to immunize children who qualify as soon as regulators approve a vaccine for them, regardless of any prior exposure. She noted that when children are hospitalized with the coronavirus, up to 30 percent of them may need intensive care.Many of those children also have other medical conditions. But as many as 70 percent of cases of multisystem inflammatory disease, a rare consequence of Covid-19 infection, occur in children who were otherwise healthy.“As a pediatrician and a parent, I would absolutely endorse that children get vaccinated, even if they have been infected,” Dr. Clarke said.Coronavirus cases are rising again in the United States, particularly in the Northeast, but so far the rise in hospitalizations has been minimal, and deaths are still dropping. Even among those who are hospitalized, “we’re seeing less oxygen use, less I.C.U. stays, and we haven’t, fortunately, seen any increase in deaths associated with them,” said the C.D.C.’s director, Dr. Rochelle Walensky. “We are hopeful that positive trends will continue.”C.D.C. researchers began assessing antibody levels in people at 10 sites early in the pandemic, and have since expanded that effort to all 50 states, the District of Columbia and Puerto Rico. The investigators use a test sensitive enough to identify previously infected people for at least a year or two after exposure.The researchers analyzed blood samples collected from September 2021 to February 2022, looking for antibodies to the virus; then they parsed the data by age, sex and geographic location. The investigators looked specifically for a type of antibody that is produced after infection, but not in people who have merely been vaccinated.Between September 2021 and December 2021, the prevalence of antibodies in the samples steadily increased by one to two percentage points every four weeks. But it jumped sharply after December, increasing by nearly 25 points by February 2022.The percentage of samples with antibodies rose to about 75 percent from about 45 percent among both children aged 11 years and younger, and adolescents aged 12 to 17.By February 2022, roughly 64 percent of adults 18 to 49, about half those 50 to 64, and about one-third of older adults had been exposed to the virus, according to the study.

Age-related changes in strength and mobility may depend on genetic variations in a critical mitochondrial enzyme, suggests a study published today in eLife.
The results help to address the question of why some individuals remain active as they age while others find it more difficult to get around. The genetic variations identified in the study can be evaluated further to identify specific mechanisms by which individuals lose mobility over time, and contribute to the prediction of these losses with aging.
Many people progressively lose muscle mass and strength as they age, which can reduce their quality of life and contribute to falls and broken bones later in life. A lack of exercise or poor diet can contribute to age-related muscle loss, but genetic factors also likely play a role.
“While aging is universal, the genetic factors that contribute to differences among individuals as they age are unclear. We wanted to examine the role that genetic variations in a mitochondrial enzyme play in age-related changes to mobility,” explains Osvaldo Villa, a PhD student at the USC Leonard Davis School of Gerontology, US. Villa is a co-first author of the study alongside PhD student Nicole Stuhr and Dr Chia-An Yen.
For their study, the team screened the roundworm Caenorhabditis elegans (C. elegans) for genetic variations that contribute to a build-up of oxidative stress, a process that can cause cell damage, in muscle tissue. They found that variations in a gene called ALH-6 were associated with oxidative stress. Over time, worms with these variations were less able to crawl and swim.
Next, the team analysed data from the U.S. Health and Retirement Study (HRS) to see if genetic variants in the human equivalent of this gene, called ALDH4A1, were also linked to age-related mobility changes. The HRS has enrolled more than 36,000 US adults aged 50 and over, and collected genetic and health information. By analysing a subset of participants with genetic data and measures of strength, the researchers found that older adults with certain variations in the ALDH4A1 gene had slower walking speeds and reduced hand strength as they aged.
“These findings suggest that variations in the ALH-6 or ALDH4A1 gene can impact muscle aging in C. elegans and humans, and may help predict muscle health in people as they age,” Stuhr says.
The team cautions that many human genes likely interact with each other, as well as diet and other factors, to influence strength and mobility as people age. More studies are needed to understand all of the genes involved in these age-related changes.
“Predictive biomarkers for muscle strength and mobility are extremely rare due to a limited amount of data on aging in humans,” concludes Senior author Sean Curran, Professor of Gerontology, Molecular and Computational Biology, and Associate Dean of Research, at the USC Leonard Davis School of Gerontology. “With the expertise of Drs Arpawong and Crimmins at the Genomic Translation Across Species Core in the USC-Buck Nathan Shock Center of Excellence in the Basic Biology of Aging, we’re now planning to partner with other researchers to allow them to integrate their genetic research models with our human gene-wide association scanning approach. Building on our work in this way could help with identifying new predictors of age-related changes in muscle health and other age-related conditions.”
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