Publisher Health

Scientists are lugging sophisticated sensors into homes in 10 cities to measure and track the pollution from gas stoves as it drifts from room to room.Every morning, as millions of Americans light up the gas stoves in their kitchens to heat some water or griddle their hash browns, they aren’t just sending delicious breakfast smells wafting through their homes. The blue flames also emit harmful pollutants like nitrogen dioxides, as well as planet-warming gases.So a team of scientists from Stanford recently embarked on a testing tour of New York City apartments to better understand the extent of the pollution and how it flows from room to room in people’s real homes. It’s part of a 10-city study that is already showing how contaminants can quickly drift into living rooms and bedrooms, sometimes far beyond the stoves that created them.Concerns over the health and climate effects of gas-burning stoves have already prompted some cities and states to seek to phase out natural gas connections in new buildings, and the federal government has also moved to strengthen efficiency standards for gas stoves. But the issue has become a polarizing one. Last week in Washington, Republicans convened a hearing of the House Oversight Committee “examining the Biden administration’s regulatory assault on Americans’ gas stoves.”On a crisp Sunday morning, the Stanford scientists made their first stop in New York City: a public-housing project in Morningside Heights in Upper Manhattan. Their first challenge: hauling 300 pounds of equipment to the 18th floor. “Hope there’s an elevator,” Rob Jackson, a professor at the Stanford Doerr School of Sustainability and the team’s leader, said warily. (There was.)Stove testers from Stanford unloading 300 pounds of gear.Calla Kessler for The New York TimesSetting up inside Tina Johnson’s home in New York.Calla Kessler for The New York TimesThe three-bedroom apartment they were visiting — home to Tina Johnson, a mother to three adult children — overlooks elevated train tracks and has an eat-in kitchen filled with the aromas of herbs and spices that she uses to make her favorite dish, an American-style ratatouille. Mrs. Johnson had just cooked a breakfast of fried eggs and potatoes.“I’m glad you’re here,” she told the researchers. A new stove had just been installed in her unit, but she still “can’t stand the smell” of the gas from it, she said. She had volunteered to participate in the study through a local climate group, Mrs. Johnson said, because she and her children have asthma and other health problems; she was eager to know what their stove did to the air they breathed.Nose-High TubesThe researchers got to work powering up their analyzers and setting up tubes, at roughly nose height, to pull in samples of air. After they took background readings, it was time to turn on the gas, a single small burner on high.The machinery quickly detected the change: a rise in concentrations of nitrogen dioxide — which, among other negative health effects, can irritate the respiratory system, aggravate symptoms of respiratory diseases and contribute to asthma. Concentrations climbed to 500 parts per billion, five times the safety benchmark for one-hour exposures set by the Environmental Protection Agency. (Concentrations of benzene, a human carcinogen that is present in cigarette smoke and car emissions, also tripled.)Ms. Johnson chose to participate in the stove-testing study because she and her children have asthma, she said, and she wanted to know the impact of the gas from the stove on their health.Calla Kessler for The New York TimesThis was with the kitchen doorway sealed off and the window closed, too. Mrs. Johnson’s kitchen also lacks a stove hood, which could help with ventilation.Opening the kitchen entrance and cracking open the window, as Mrs. Johnson said she often did while cooking, brought nitrogen dioxide levels down to about 200 parts per billion. But that also meant fumes from the stove were now seeping into the rest of the apartment.In one bedroom, nitrogen dioxide concentrations reached about 70 parts per billion, below the E.P.A. threshold but significantly above the World Health Organization’s standards for chronic exposure.There has been mounting scientific evidence of the health risks of gas stoves. One paper published late last year found that gas stoves may be linked to nearly 13 percent of childhood cases of asthma in the United States. Previous research shows that gas stoves have led to more exacerbated asthma symptoms as well.There are a few simple steps that people can take to reduce the danger, such as opening the windows and buying an air purifier.One characteristic of New York residences, Dr. Jackson later said, is that people tend to go about their lives at home — working, relaxing, sleeping — far closer to the gas stove than those in a suburban setting. In all, he said, “the biggest surprise for me has been just how high concentrations get, but also how quickly the pollutants spread around the home.”Air quality readings from the kitchen.Calla Kessler for The New York Times‘Dinner Party Scenario’The next day, the team was back testing at another location, this time at an Airbnb apartment in Central Harlem. Their goal: recreate a “big family or dinner party scenario,” said Yannai Kashtan, a Ph.D. candidate in earth system science at Stanford and a member of the research team.To limit their own exposure, the team members camped out on a balcony, with sweeping views of Upper Manhattan, holding their breath and running in and out to check on levels.In the course of about 40 minutes, levels of nitrogen dioxide topped 200 parts per billion in the living room, 300 parts per billion in the bedroom and 400 parts per billion in the kitchen, or double, triple and quadruple thresholds set by the E.P.A. for one-hour exposures. Benzene concentrations also tripled after the stove was turned on.This stove came with a hood. “But feel this,” Mr. Kashtan said, his hand in a stream of hot air that was blowing out from the hood’s edge instead of venting outdoors. That meant the hood “doesn’t make much difference” to the bad air, he said.In all, the team conducted daylong testing at eight New York City apartments, including a Brooklyn home where the researchers puzzled over a New York peculiarity: windows sealed with plastic. That was for insulation, said Nina Domingo, who lives in the ground-floor unit with two housemates. But it also meant poor ventilation, which was alarming, given that the kitchen also lacked a hood that vented to the outside.In the immediate kitchen area, nitrogen dioxide concentrations quickly rose to about 2.5 times the E.P.A. threshold.Ms. Domingo.Calla Kessler for The New York TimesTesting the air in Ms. Domingo’s apartment in Brooklyn.Calla Kessler for The New York TimesThe team’s results are preliminary, but they are in line with a body of scientific research that has linked gas stove emissions to harmful pollution affecting both climate change and public health. Previous research has also shown that emissions continue to be released when a stove is turned off because stoves can leak natural gas, which is mostly methane, a potent greenhouse gas.Ms. Domingo, who works in technology, said she was aware of the concerns over pollution from stoves, and her previous apartment had, in fact, come with an electric induction stove, a particularly efficient design. But when she decided to upgrade to a larger home last summer, competition for apartment units was so fierce that she “couldn’t be picky,” she said.Change could be on the horizon.More than 60 percent of American households already use electricity to cook, and the Biden administration has proposed to expand gas stove efficiency rules, with an estimated $100 million in energy savings for people on top of the climate and health benefits. Several cities in mostly blue states have passed or considered bans on new gas hookups, effectively requiring electric cooking and heating in new construction, though some red states have moved to pre-empt such bans.The Stanford team, which has already tested stoves in cities including San Francisco; Denver; Houston; and Melbourne, Australia, is heading to Washington next. It also plans to test in Europe and Asia.What do they expect to find in Asian cities? Even smaller living spaces, which could mean higher concentrations of pollutants, and more exposure. It’s a global problem, they said. Just how bad a problem, they’re about to find out.

The decision gives the Purdue Pharma owners long-sought protection, but it will release billions of dollars from their fortune to states and communities to help cope with the costs of addiction.Members of the Sackler family, the billionaire owners of Purdue Pharma, will receive full immunity from all civil legal claims — current and future — over their role in the company’s prescription opioids business, a federal appeals court panel ruled on Tuesday.The ruling gives the family the sweeping protection that it has been demanding for years, in exchange for payment of up to $6 billion of the family’s fortune to help address the ongoing ravages of the opioid crisis.That money, plus the company’s initial outlay of $500 million, can now begin to be dispensed to states and communities for addiction treatment and prevention programs, needs that soared during an epidemic that has grown far beyond abuse of Purdue’s signature prescription painkiller drug, OxyContin.Unless it is successfully appealed to the Supreme Court — an unlikely prospect, legal experts said — the new ruling will close the door on Purdue’s hotly contended bankruptcy restructuring, which began nearly four years ago. The bankruptcy is at the core of a plan intended to resolve thousands of opioid cases against the company nationwide, plus roughly 400 against individual Sackler family members.According to the plan, Purdue would be restructured into a new entity called Knoa Pharma that will manufacture medications for addiction reversal and treatment as well as continue to produce other drugs, including OxyContin. It will be overseen by a public board. Over time, Knoa Pharma is expected to contribute at least many hundreds of millions dollars more to plaintiffs.Some close observers of the Purdue case applauded the ruling, calling it a pragmatic reading that could now loosen up billions of dollars for states, local governments, tribes and individuals who sued Purdue for its early and aggressive role in marketing OxyContin as a nonaddictive pain treatment.“It’s time to put this bankruptcy behind us. Victims have been waiting for too long to recover,” said Ryan Hampton, an advocate for opioid victims who served as the co-chairman of the Purdue creditor’s committee.He added: “The system is far from perfect, but the true injustice will be if this victims’ settlement is held up any longer.”But others said the Sacklers had received a significant pass. “Bankruptcy was not meant to be an alternative justice system for powerful corporations and their superrich owners. But that is the effect and perception when courts read the law to provide extraordinary protections well beyond what Congress authorized,” said Melissa B. Jacoby, a law professor at the University of North Carolina at Chapel Hill.A bankruptcy filing typically puts a temporary halt on a company’s creditors, including on lawsuits. The major issue in this case was that even though Purdue had filed for bankruptcy, the Sacklers, as individuals, had not. As a result, plaintiffs who fought the plan contended, the Sacklers should not receive the benefit of their company’s liability protection.The Sacklers stepped down from Purdue’s board of directors in 2018 and have had no direct involvement in the company since then.Judge Eunice C. Lee of the United States Court of Appeals for the Second Circuit, who wrote Tuesday’s opinion for a three-judge panel, found that the bankruptcy code permits corporate owners who haven’t filed for personal bankruptcy to receive liability protection under certain circumstances.“Bankruptcy is inherently a creature of competing interests, compromises, and less than perfect outcomes,” she wrote. “Because of these defining characteristics, total satisfaction of all that is owed — whether in money or in justice — rarely occurs.”Quoting from a bankruptcy ruling in a 2019 case that did not involve Purdue, Judge Lee also stressed that the releases granted to the Sacklers “ ‘are not a merit badge that somebody gets in return for making a positive contribution to a restructuring,’ nor are they ‘a participation trophy’ or a ‘gold star for doing a good job.’ ”The Sacklers’ liability protection does not extend to criminal prosecutions, should any ever be filed.Purdue filed for bankruptcy in September 2019, as the rising opioid cases against the company turned into a torrent.Tuesday’s ruling came more than a year after oral arguments before the Second Circuit panel. As months passed, thousands of litigants expressed growing frustration that the case remained unresolved, with promised payments held in abeyance even as the opioid epidemic itself, now marked by fentanyl use, continued to surge.The ruling was a win for Purdue, which appealed a decision by a federal district judge, who overturned a settlement that had originally been approved by a bankruptcy court judge in 2021. But most of the parties that had appealed the 2021 plan eventually wound up dropping their objections, after the Sacklers increased their payout offer by roughly $1.73 billion.The only objectors who remain include several Canadian municipalities, a few individuals and the U.S. Trustee, a Justice Department program that is the watchdog of the bankruptcy system. Ms. Jacoby, the North Carolina law professor, said that because the last objecting states had agreed to the Purdue plan, the U.S. Trustee’s argument for pursuing the case would not be robust.The U.S. Trustee declined to comment on Tuesday’s ruling.In a statement after the ruling was issued, Purdue called the decision “a victory for Purdue’s creditors, including the states, local governments and victims who overwhelmingly support the plan of reorganization.”“Our focus going forward is to deliver billions of dollars of value for victim compensation, opioid crisis abatement and overdose rescue medicines,” the statement continued. “Our creditors understand the plan is the best option to help those who need it most, the most fair and expeditious way to resolve the litigation and the only way to deliver billions of dollars in value specifically to fund opioid crisis abatement efforts.”The families of the two founding brothers of Purdue, Dr. Mortimer Sackler and Dr. Raymond Sackler, both deceased, said in a joint statement: “The Sackler families believe the long-awaited implementation of this resolution is critical to providing substantial resources for people and communities in need. We are pleased with the Court’s decision to allow the agreement to move forward and look forward to it taking effect as soon as possible.”

Since it was identified in 1984 as the cause of Acquired Immune Deficiency Syndrome (AIDS), the human immunodeficiency virus (HIV) has infected more than 80 million people and been responsible for some 40 million deaths worldwide, according to the World Health Organization (WHO). Currently, the WHO reports more than 38 million people globally live with the retrovirus, and each year, another 1 million new cases are diagnosed. While antiretroviral therapy helps keep HIV in check, patients must stay on their medication to prevent the development of AIDS.
Scientists have spent years trying to develop an effective HIV vaccine, but none have proven successful. Based on findings from a recently published study, a Johns Hopkins Medicine-led research team may have put science one step closer to that goal.
Their work first appeared online April 14, 2023, in the Journal of Experimental Medicine, and will be formally published in the July 3, 2023, issue.
Using a laboratory technique created at Johns Hopkins Medicine in 2010, the study researchers replicated the cellular environment in which specialized immune cells called antigen presenting cells (APCs) break down proteins derived from HIV and make them visible (“presented”) to the immune system’s frontline of defense, cells known as CD4+ T lymphocytes, or helper T cells.
“Our simple method, called reductionist cell-free antigen processing, reproduces in a test tube the complex events that occur in the human immune system as a response to antigens, foreign invaders to the body such as viruses like HIV,” says senior study author Scheherazade Sadegh-Nasseri, Ph.D., professor of pathology at the Johns Hopkins University School of Medicine. “When APCs chew up proteins from an antigen and present the fragments, known as antigenic epitopes, on their surface, the epitopes become visible to helper T cells and initiate an immune response.”
“If we can identify which epitopes are ‘immunodominant’ — the ones that elicit the strongest immune system response to the virus — then we may have the essential ingredients for the long-sought recipe to make an effective HIV vaccine,” explains Sadegh-Nasseri.

Epitopes that are immunodominant have structures that uniquely fit like a lock and key with cell-surface proteins on APCs known as major histocompatibility molecules, or MHCs.
“If you think of an HIV epitope as a hot dog and the MHC as a bun, the ‘meal’ is what gets presented to CD4+ T cells,” says lead study author Srona Sengupta, an M.D./Ph.D. candidate in immunology at the Johns Hopkins University School of Medicine. “T cells that can recognize the HIV epitope-MHC complex as foreign become activated and signal B cells — a different type of immune cell that produces antibodies, in this case, specific to HIV. Antibodies bind to the virus, destroying already infected cells or preventing HIV from entering uninfected ones — the key functions of an effective vaccine.”
Sadegh-Nasseri says previous efforts to map and identify the desired immunodominant epitopes have proven unreliable.
“Traditional methods use a ‘brute-force’ system where synthetic peptides representing portions of real HIV proteins are tested in the hopes that some will stimulate an immune response and direct researchers to the epitopes needed for vaccine development,” says Sadegh-Nasseri. “Not only is this strategy hit or miss, but the method doesn’t allow for the real-world chemical and molecular interactions that can impact how epitopes are produced and function.”
This, she explains, is a major reason why an effective HIV vaccine remains elusive.

“Our cell-free antigen processing system,” says Sadegh-Nasseri, “replicates how epitopes are actually processed in the APC’s cellular environment and become presented, including any influencing factors that may come into play.”
“This enabled us to study nearly the entire HIV proteome [all of the proteins produced by the virus] and distinctly identify epitopes that are selected for presentation to CD4+ T cells by a chaperone protein called HLA-DM,” says Sengupta. “That’s important because we know that HIV epitopes processed and edited by HLA-DM are immunodominant.”
Sengupta adds that 35 epitopes identified in the recent studies were previously unknown.
The researchers say that their analysis using the cell-free antigen processing system revealed three important findings: (1) the epitopes identified are indeed generated in humans who are HIV positive and lead to the development of memory CD4+ T cells (the immune cells that remember an antigen for future encounters); (2) the processing system can be very useful in predicting which parts of HIV protein antigens may yield the immunodominant epitopes that can be included in new vaccines; and (3) the system’s use of full-length natural proteins ensures that the impacts of any cellular environmental influences (such as those causing modifications of viral epitopes after infected host cells have produced them) are taken into account.
Current analysis technologies lack such abilities, say Sadegh-Nasseri and Sengupta.
“Interestingly, we identified several epitopes that were modified by sugar groups, a potentially important finding for vaccine developers to know, but one that traditional analysis would have missed,” says Sengupta.
Sadegh-Nasseri and Sengupta say that their team will continue to refine the immunodominant epitope identification system and use the data from future analyses to enhance the ability of vaccine developers to design robust and effective protective measures against not only HIV, but also SARS-CoV-2 (the virus that causes COVID-19) and other viral pathogens.
Along with Sadegh-Nasseri and Sengupta, the members of the study team from Johns Hopkins Medicine and Johns Hopkins University are Nathan Board, Tatiana Boronina, Robert Cole, Madison Reed, Kevin Shenderov, co-senior author Robert Siliciano, Janet Siliciano, Andrew Timmons, Robin Welsh, Weiming Yang and Josephine Zhang. The team also includes Steven Deeks and Rebecca Hoh from the University of California San Francisco, and Aeryon Kim from Amgen Inc.

A group of world leading health and scientific experts are calling on the aviation industry to take action to protect passengers and aircrew from dangerous cabin fumes which they say have led to a new emerging disease.
Led by former pilot and leading global aviation health researcher Dr Susan Michaelis, the specialists have released the first medical protocol of its kind to help treat those effected by contamination of the aircraft cabin breathing air supply and collect data on contamination events.
The International Fume Events Task Force, made up of 17 doctors, occupational health specialists, toxicologists, epidemiologists and aviation experts, have spent six years researching and preparing the evidence and guidance. The result is a unique protocol for medical staff and non-medically trained airline staff which outlines the actions and investigations they should carry out when a person has been exposed to fumes or fume events.
Aircrew and passengers are exposed to chronic background low-levels of engine oils and hydraulic fluids leaking into the aircraft air supply during every flight. They can also experience adverse effects from more irregular ‘fume’ events, which mark incidents when there’s a noticeable level of contaminants in the cabin.
Dr Michaelis, who is an Honorary Senior Research Fellow at the University of Stirling, said: “This has been happening for the last 70 years and reports of air crew becoming unwell continue to rise.
“Currently, when aircrew or passengers become unwell, whether they are still on the plane, suffer symptoms in the days or weeks to come, or report illness in the years that follow, there’s nothing in the medical books, there’s no guidance material for the aviation industry or medical professionals and very often they get turned away or are given minimal testing.

“This new medical protocol has been written by internationally recognised experts and presents a consensus approach to the recognition, investigation and management of people suffering from the toxic effects of inhaling thermally degraded engine oil and other fluids contaminating the air conditioning systems in aircraft, and includes actions and investigations for in-flight, immediately post-flight and late subsequent follow up.
“All of the data and evidence collected strongly suggests a causal connection between the contaminants from the oils and hydraulic fluids and people becoming unwell. This is the first comprehensive and systematic approach for documenting and gathering further epidemiological data in what is a discreet and emerging occupational health syndrome.”
The medical protocol and an accompanying narrative review have been published in the open access peer reviewed journal, Environmental Health.
The narrative review illustrates the diffuse and consistent pattern of adverse effects, as documented by aircrew and some passengers, after breathing these fumes onboard and incorporates the findings from fume event reports and documented ill health effects that were collected over decades in multiple countries and regions.
Professor Andrew Watterson of the University of Stirling said “This is a globally important and ground-breaking study using a narrative review of a significant and complex problem for those exposed to aircraft cabin air supply fumes that result in a range of often serious adverse effects.
“It has generated a very useful tool in the process, based on recent research, in the form of a protocol for identifying, assessing and better documenting those effects in the future.”
Exposure to aircraft contaminated air and fume events is associated with documented aircrew impairment and incapacitation, jeopardizing the safety of the flight. These exposures are known to cause foggy thinking, dizziness, fatigue and impaired short-term memory and cognitive thinking. It can also cause neurological, respiratory and cardiac complaints, while other studies have drawn links with various cancers.

While it can take years for the pharmaceutical industry to create medicines capable of treating or curing human disease, a new study suggests that using generative artificial intelligence could vastly accelerate the drug-development process.
Today, most drug discovery is carried out by human chemists who rely on their knowledge and experience to select and synthesize the right molecules needed to become the safe and efficient medicines we depend on. To identify the synthesis paths, scientists often employ a technique called retrosynthesis — a method for creating potential drugs by working backward from the wanted molecules and searching for chemical reactions to make them.
Yet because sifting through millions of potential chemical reactions can be an extremely challenging and time-consuming endeavor, researchers at The Ohio State University have created an AI framework called G2Retro to automatically generate reactions for any given molecule. The new study showed that compared to current manual-planning methods, the framework was able to cover an enormous range of possible chemical reactions as well as accurately and quickly discern which reactions might work best to create a given drug molecule.
“Using AI for things critical to saving human lives, such as medicine, is what we really want to focus on,” said Xia Ning, lead author of the study and an associate professor of computer science and engineering at Ohio State. “Our aim was to use AI to accelerate the drug design process, and we found that it not only saves researchers time and money but provides drug candidates that may have much better properties than any molecules that exist in nature.”
This study builds on previous research of Ning’s where her team developed a method named Modof that was able to generate molecule structures that exhibited desired properties better than any existing molecules. “Now the question becomes how to make such generated molecules, and that is where this new study shines,” said Ning, also an associate professor of biomedical informatics in the College of Medicine.
The study was published today in the journal Communications Chemistry.
Ning’s team trained G2Retro on a dataset that contains 40,000 chemical reactions collected between 1976 and 2016. The framework “learns” from graph-based representations of given molecules, and uses deep neural networks to generate possible reactant structures that could be used to synthesize them. Its generative power is so impressive that, according to Ning, once given a molecule, G2Retro could come up with hundreds of new reaction predictions in only a few minutes.
“Our generative AI method G2Retro is able to supply multiple different synthesis routes and options, as well as a way to rank different options for each molecule,” said Ning. “This is not going to replace current lab-based experiments, but it will offer more and better drug options so experiments can be prioritized and focused much faster.”
To further test the AI’s effectiveness, Ning’s team conducted a case study to see if G2Retro could accurately predict four newly released drugs already in circulation: Mitapivat, a medication used to treat hemolytic anemia; Tapinarof, which is used to treat various skin diseases; Mavacamten, a drug to treat systemic heart failure; and Oteseconazole, used to treat fungal infections in females. G2Retro was able to correctly generate exactly the same patented synthesis routes for these medicines, and provided alternative synthesis routes that are also feasible and synthetically useful, Ning said.
Having such a dynamic and effective device at scientists’ disposal could enable the industry to manufacture stronger drugs at a quicker pace — but despite the edge AI might give scientists inside the lab, Ning emphasizes the medicines G2Retro or any generative AI creates still need to be validated — a process that involves the created molecules being tested in animal models and later in human trials.
“We are very excited about generative AI for medicine, and we are dedicated to using AI responsibly to improve human health,” said Ning.
This research was supported by Ohio State’s President’s Research Excellence Program and the National Science Foundation. Other Ohio State co-authors were Ziqi Chen, Oluwatosin Ayinde, James Fuchs and Huan Sun.

The early stages of embryonic development contain many of life’s mysteries. Unlocking these mysteries can help us better understand early development and birth defects, and help develop new regenerative medicine treatments.
Researchers based at the Australian Regenerative Medicine Institute (ARMI) at Monash University have characterised a critical time in mammalian embryonic development using powerful and innovative imaging techniques, with their work published in Nature Communications.
“Just a few days into the journey of embryogenesis, when turning into 16 cells, the embryo must make its first difficult decision — which of its cells will give rise to the embryo or will become extra-embryonic tissue, for example, placenta,” explained lead researcher Dr Jennifer Zenker.
In this study, the research team has discovered how this decision-making process is facilitated by capturing the inner organisation of single cells of the early embryo.
“Ribonucleic acid, RNA, plays a key role here. At the 16-cell stage, the different subtypes of RNA, named rRNAs, mRNAs and tRNAs, are sorted to the two ends of a cell called apical and basal side. The distribution of RNA subtypes determines what the next generation of cells of the embryo will become,” Dr Zenker said.
Interestingly, while most mRNAs and tRNAs remain parked at the apical side, most rRNA molecules travel down to the basal side hitchhiking on organelles called lysosomes. Even though retaining less overall RNA content, the apical sides of outer 16-cell stage cells contain the full collection of RNAs and other factors required for protein production.
The crowded basal side, however, is occupied predominantly with rRNAs. Daughter cells obtaining the more active protein factories of the apical side, are more transformable and specialise into the future placenta. The daughter cells which retain their potential to still become any type of cell of the adult organism, called pluripotency, receive the less translationally active bulk of rRNA.
This decision and many like it, which is known as cell fate, are important in development as it determines how these early cells reach their final cell type, such as skin cells, heart muscle cells and brain cells. For regenerative medicine, being able to orchestrate cell fate opens up the capacity to generate new stem cell-based treatments for a number of diseases and conditions.
“As in real life, cells can influence the direction of their own future by getting organised early. Our research may open new ways to predict and direct cell fate decisions,” Dr Zenker said.

A scientific team from the University of Barcelona and the CIBERobn has designed a strategy to fight obesity and diabetes in mice through ex vivo gene therapy which consists of implanting cells that have been manipulated and transformed in order to treat a disease. This is the first study to apply the ex vivo gene therapy technique to generate and implant cells that express the CPT1AM protein, an enzyme that plays a decisive role in many metabolic diseases such as obesity.
The study, published in the journal Metabolic Engineering, is led by Professor Laura Herrero, from the Faculty of Pharmacy and Food Sciences and the Institute of Biomedicine of the University of Barcelona (IBUB), and from the Physiopathology of Obesity and Nutrition Networking Biomedical Research Centre (CIBERobn).
Cell therapy describes the process of introducing new cells into a tissue in order to fight a disease. Cell therapies are currently focused on addressing hereditary diseases — with and without the help of gene therapy — or degenerative diseases.
“In this new therapy, animal models have been implanted subcutaneously stem cells derived from adipose tissue, differentiated into adipocytes, so that they can express an active form of the CPT1AM protein, an enzyme located in the mitochondria that is key in lipid oxidation and is related to metabolic diseases,” says Laura Herrero, a member of the UB Department of Biochemistry and Physiology.
“As a result, in obese mice, it has been possible to reduce weight, fatty liver (hepatic steatosis), cholesterol and glucose levels. In conclusion, the implantation of adipocytes expressing the mitochondrial enzyme CPT1AM helps to reduce obesity and glucose intolerance in mice.”
As the cell transformation process takes place outside the body of the organism, this type of therapy is much easier to carry out and allows for greater control of the altered cells.
Obesity and cell therapy
Obesity and associated metabolic disorders represent a worldwide health and social problem, which is why new therapeutic approaches are urgently needed. Adipose tissue plays a key role in regulating energy balance, and adipose-derived mesenchymal stem cells — cells with the ability for self-renewal — have gained interest in cell therapy.
“Specifically, carnitine palmitoyltransferase 1A (CPT1A) is the enzyme that controls mitochondrial fatty acid oxidation. Our aim was to generate adipocytes that could express a constitutively active form of CPT1A — CPT1AM — capable of burning excess fat and improving the obese metabolic phenotype of mice after implantation.”
The results of the new study support the future clinical use of this ex vivo gene therapy approach as a new strategy to reduce obesity and cholesterol rates in the population.
This preclinical study could open the doors to future therapeutic strategies to address the treatment of obesity, which today represents a global health problem.
“To approximate the therapy in humans, we need to optimize several processes such as the quality and viability of stem cells from adipose tissue isolated from people with obesity, the percentage of infection with lentivirus, and the number of cells used for transplantation,” concludes researcher Laura Herrero.

Low sexual satisfaction in middle age may serve as an early warning sign for future cognitive decline, according to a new study led by Penn State researchers. The study, which tracked associations between erectile function, sexual satisfaction and cognition in hundreds of men aged 56 through 68, found that declines in sexual satisfaction and erectile function were correlated with future memory loss.
The study, published in the latest issue of the journal Gerontologist, is the first to longitudinally track sexual satisfaction in tandem with sexual health and cognition, the researchers state, and its findings point to a potential novel risk factor for cognitive decline.
“What was unique about our approach is that we measured memory function and sexual function at each point in the longitudinal study, so we could look at how they changed together over time,” said Martin Sliwinski, professor of human development and family studies at Penn State and co-author on the study. “What we found connects to what scientists are beginning to understand about the link between life satisfaction and cognitive performance.”
The study explored the relationship between physical changes like the microvascular changes relevant for erectile function, and psychological changes, such as lower sexual satisfaction, to determine how the changes relate to cognition. They examined the shifts starting in middle age because it represents a transition period where declines in erectile function, cognition and sexual satisfaction begin to emerge.
Sliwinski added that while the team discovered a strong correlation between the three health factors, they can only speculate as to the cause.
“Scientists have found that if you have low satisfaction generally, you are at a higher risk for health problems like dementia, Alzheimer’s disease, cardiovascular disease and other stress-related issues that can lead to cognitive decline,” he said. “Improvements in sexual satisfaction may actually spark improvement in memory function. We tell people they should get more exercise and eat better foods. We’re showing that sexual satisfaction also has importance for our health and general quality of life.”
For the study, the researchers used survey data from 818 men who participated in the Vietnam Era Twin Study of Aging. Through neuropsychological tests, such as tests of memory and processing speed, they examined cognitive changes of participants over the 12-year span from age 56 to 68, adjusting for participants’ cognitive ability in young adulthood. Their erectile function and sexual satisfaction were measured alongside cognition, using the International Index of Erectile Function, a self-reported assessment for male sexual health. The researchers then built a statistical model to understand how the three variables changed as individuals aged.

“Research on sexual health has historically focused on quantifiable facets of sexuality like number of sexual partners or frequency of sexual activity,” said Riki Slayday, a doctoral candidate at Penn State and lead author on the study. “What we were interested in is the perception of that activity, how someone feels about their sex life, and how that influences cognitive function, because multiple people could be in the same situation physically but experience completely different levels of satisfaction.”
The study found that decreases in erectile function and sexual satisfaction were both associated with memory decline, which the researchers say points to a connection between psychological and physical health.
“When we mapped the relationship over time, we found increases or decreases in erectile function and sexual satisfaction were associated with concurrent increases or decreases in cognitive function,” Slayday said. “These associations survived adjustment for demographic and health factors, which tells us there is a clear connection between our sex lives and our cognition.”
Prior studies have found a link between microvascular changes and changes in erectile function over time. In fact, the active ingredient in Viagra (Sildenafil) was originally developed to treat cardiovascular problems, Sliwinski explained, so the connection between vascular health and erectile function is well understood. How erectile function connects to other aspects of health should be an area of focus for future research, he added.
Increasing the assessment and monitoring of erectile function as a vital sign of health may help identify those at risk of cognitive decline before their 70s, he said. The researchers note that the older adult population in the U.S. is expected to double over the next 30 years, which means twice as many people will likely enter their 60s and experience declines in erectile function and sexual satisfaction.
“We already have a pill for treating erectile dysfunction. What we don’t have is an effective treatment for memory loss,” Sliwinski said. “Instead of the conversation being about treating ED, we should see that as a leading indicator for other health problems and also focus on improving sexual satisfaction and overall well-being, not just treating the symptom.”
Other co-authors on the paper are Tyler Bell, Teresa Warren, William Kremen and Carol Franz of the University of California San Diego; and Michael Lyons, Rosemary Toomey and Richard Vandiver of Boston University.
The work was supported the National Institute on Aging at the National Institutes of Health.

Being obese significantly increases the chances of also developing mental disorders. This applies to all age groups, with women at higher risk than men for most diseases, as a recent study of the Complexity Science Hub and the Medical University of Vienna shows. The results were published in the specialist journal Translational Psychiatry.
“We analyzed a population-wide national registry of inpatient hospitalizations in Austria from 1997 to 2014 in order to determine the relative risks of comorbidities in obesity and identify statistically significant sex differences,” explains Elma Dervic of the Complexity Science Hub. Consequently, it became evident that an obesity diagnosis significantly enhances the likelihood of a wide range of mental disorders across all age groups — including depression, nicotine addiction, psychosis, anxiety, eating and personality disorders. “From a clinical point of view, these results emphasise the need to raise awareness of psychiatric diagnoses in obese patients and, if necessary, to consult specialists at an early stage of diagnosis,” says Michael Leutner of the Medical University of Vienna.
FIRST DIAGNOSIS: OBESITY
“In order to find out which illness typically appeared prior and subsequently to the obesity diagnosis, we had to develop a new method,” explains Dervic. This allowed the researchers to determine if there were trends and typical patterns in disease occurrence.
In case of all co-diagnoses, with the exception of the psychosis spectrum, obesity was in all likelihood the first diagnosis made prior to the manifestation of a psychiatric diagnosis. “Until now, physicians often considered psychopharmacological medications to cause the association between mental disorders and obesity as well as diabetes. This may be true for schizophrenia, where we see the opposite time order, but our data does not support this for depression or other psychiatric diagnoses,” explains Alexander Kautzky from Department of Psychiatry and Psychotherapy of the Medical University Vienna. However, whether obesity directly affects mental health or whether early stages of psychiatric disorders are inadequately recognised is not yet known.
GREATER IMPACT IN WOMEN
Surprisingly, the researchers found significant gender differences for most disorders — with women showing an increased risk for all disorders except schizophrenia and nicotine addiction.
While 16.66% of obese men also suffer from nicotine abuse disorder, this is only the case in up to 8.58% of obese women. The opposite is true for depression. The rate of diagnosed depressive episodes was almost three times higher in obese women (13.3% obese; 4.8% non-obese). Obese men were twice as likely to be affected (6.61% obese; 3.21% non-obese).
COUNTERACT AT A YOUNG AGE
At present, obesity is a highly prevalent disease worldwide and affects more than 670 million people. The fact that the disease promotes metabolic disorders and serious cardio-metabolic complications (diabetes mellitus, arterial hypertension, and dyslipidaemia) has already been extensively researched.
Since this study now also shows that obesity often precedes severe mental disorders, the findings underscore its importance as a pleiotropic risk factor for health problems of all kinds. This is primarily true for young age groups, where the risk is most pronounced. For this reason, thorough screening for mental health problems in obese patients is urgently needed to facilitate prevention or ensure that appropriate treatment can be given, so the researchers conclude.

Complicated, hard-to-heal wounds are a growing medical problem and there are currently only two drugs approved with proven efficacy. In a new study on humans, researchers at Uppsala University show that treatment with a specific type of modified lactic acid bacteria works well and has a positive effect on the healing of wounds.
In several controlled preclinical models, the research team behind the new study has previously demonstrated accelerated wound healing after topical treatment (treatment on the skin) using lactic acid bacteria, or Limosilactobacillus reuteri, genetically modified to produce the chemokine CXCL12 (ILP100-Topical).
The researchers can now show data from the first clinical study on humans, in which the main objective was to establish safety and tolerability. Other objectives were to see clinical and biological effects on wound healing using traditionally accepted methods, as well as more exploratory and traceable measurements.
36 healthy volunteers were included in the study with a total of 240 induced wounds studied. The study’s design and methodology are described in more detail below.
The results show that treatment using ILP100-Topical was safe and well tolerated among all individuals and doses, and neither ILP100 nor CXCL12 could be detected in locations beyond the wounds. A significantly higher proportion of healed wounds (p=0.020) was seen on day 32 using multi-dose ILP100-Topical compared to saline and placebo (76% (73/96) and 59% (57/96) healed wounds respectively) when the results from the multi-dose-treated wounds were pooled. In addition, the time to first recorded healing was reduced by an average of 6 days, and by 10 days at the highest dose. The mechanism of action of ILP100-Topical was also confirmed when the treatment resulted in increased CXCL12-positive cells in the wounds, as well as increased blood flow around the wounds during the healing phase.
“Our study shows that bacteria modified to produce and deliver human protein for local effects can be used as drugs to accelerate the healing of wounds. This is the first time this has been shown in controlled human studies, and it can be expected that the effect is greater in patients with diseases that negatively affect wound healing,” explains Mia Phillipson, Professor at the Department of Medical Cell Biology at Uppsala University.
The favourable safety profile and the beneficial effects on wound healing observed here support further clinical development of ILP100-Topical for the treatment of complex and hard-to-heal wounds in patients, which is already under way.
Many immune-active proteins are inherently unstable and degrade quickly, so supplying them from lactic acid bacteria to the exact site of action is one way to develop them as drugs.
“The potential is really endless when you consider how important a role proteins play in various processes in the body, and how many diseases we currently do not have good enough treatments for. We have already produced another drug candidate to cure and reduce inflammation in the gut of cancer patients — ILP100-Oral — and in the future we will start a research project with another chemokine for the treatment of lung diseases,” concludes Phillipson.
Methods: SITU-SAFE is an adaptive, randomised, double-blind, placebo-controlled, phase 1 study (EudraCT 2019-000680-24) consisting of a single ascending dose (SAD) part for each participant and a multiple ascending dose (MAD) part for each participant. Both parts of the study each consisted of three dose cohorts. A total of 240 wounds were induced on the upper arms of 36 healthy volunteers, including 4 wounds (2/arm) in 12 participants in the SAD arm, and 8 wounds (4/arm) in 24 participants in the MAD arm. The wounds were randomised for treatment using a placebo, saline or ILP100-Topical. The study was conducted at the Phase 1 unit at Uppsala University Hospital in Uppsala, Sweden, and sponsored by Ilya Pharma.