Publisher Health

People who are overweight or obese have a significantly increased risk of developing diabetes, but exactly how that happens is not well understood.
A new study at Washington University School of Medicine in St. Louis may help explain how excess weight can contribute to diabetes and may provide researchers with a target to help prevent or delay diabetes in some of those at risk. The findings suggest that many people with elevated levels of insulin — an early marker of diabetes risk — also have defects in an enzyme important to the processing of a key fatty acid from the diet.
The research is published Jan. 11 in the journal Cell Metabolism.
“Between 30 million and 40 million people in the United States have Type 2 diabetes, and another 90 million to 100 million have risk factors that make them likely to develop Type 2 diabetes in the future,” said senior investigator Clay F. Semenkovich, MD, director of the Division of Endocrinology, Metabolism & Lipid Research at the School of Medicine. “Many at risk for diabetes have elevated levels of insulin, a hallmark of insulin resistance and a signal that means trouble may be brewing. If we could intervene before they actually develop diabetes, we might be able to prevent significant health problems — such as heart disease, chronic kidney disease, nerve damage, vision loss and other problems — in a great number of people.”
When a person has too much body fat, it signals beta cells in the pancreas to secrete more insulin. When insulin levels become elevated and remain high, the body can become resistant to insulin, and eventually the beta cells that secrete insulin can fail, leading to diabetes.
Studying human tissue samples, Semenkovich, the Irene E. and Michael M. Karl Professor; first author Guifang Dong, PhD, a senior scientist; Xiaochao Wei, PhD, an associate professor of medicine; and other Washington University researchers found that the overproduction of insulin involves a process called palmitoylation. This is the process by which cells attach the fatty acid palmitate to proteins.

Thousands of human proteins can be attached to palmitate, but the researchers found that when this fatty acid isn’t removed from proteins in beta cells, diabetes is the end result. Examining tissue samples from people who were thin or overweight, and with and without diabetes, the researchers found that the people with diabetes were deficient in an enzyme that removes palmitate from beta cells.
“They hyper-secrete insulin because this process goes awry, and they can’t appropriately regulate the release of insulin from beta cells,” Semenkovich explained. “Regulating insulin release is controlled in part by this palmitoylation process.”
With colleagues David W. Piston, PhD, the Edward W. Mallinckrodt Jr. Professor and head of the Department of Cell Biology & Physiology, Maria S. Remedi, PhD, a professor of medicine and of cell biology & physiology, and Fumihiko Urano, MD, PhD, a professor of medicine and of pathology & immunology, the research team also genetically engineered a mouse that was deficient in the enzyme called APT1, an enzyme responsible for palmitate removal from proteins. The engineered mice went on to develop diabetes.
Because impaired APT1 function contributed to diabetes risk, the researchers worked with the university’s Center for Drug Discovery to screen and identify compounds that can increase the activity of the APT1 enzyme.
“We’ve found several candidate drugs, and we’re pursuing those,” Semenkovich said. “We think that by increasing APT1 activity, we might reverse this process and potentially prevent people at risk from progressing to diabetes.”
Although he said the new findings identifying APT1 as a target are an important step, Semenkovich explained that APT1 is only one treatment target among many.
“There are several ways that Type 2 diabetes may develop,” he said. “This enzyme is not the answer, but it’s an answer, and it appears we have some promising tools that might keep some people with prediabetes from developing diabetes.”
Dong, G, Adak S, Spyropoulos G, Zhang Q, Feng C, Yin L, Speck SL, Shyr Z, Morikawa S, Ktamura RA, Kathayat RS, Dickinson BC, Ng XW, Piston DW, Urano F, Remedi MS, Wei X, Semenkovich CF. Palmitoylation couples insulin hypersecretion with beta cell failure in diabetes. Cell Metabolism, Jan. 11, 2023.
The study was funded with support from the National Institute of Diabetes and Digestive and Kidney Diseases; the National Heart, Lung, and Blood Institute; and the National Institute of General Medical Sciences of the National Institutes of Health (NIH). Grant numbers: DK020579, DK101392, DK056341, DK115972, DK123301, DK112921, F30 DK131830, T32 HL125241, HL157154, and GM119840. Additional funding provided by the Washington University Centene Personalized Medicine Initiative, a China Scholarship Council grant, the Manpei Suzuki Diabetes Foundation and JSPS Overseas Research Fellowships.

Now that California’s tobacco prohibitions are in place, some Camel and Newport items are billed as newly “fresh” or “crisp” non-menthol versions.R.J. Reynolds has wasted no time since California’s ban on flavored tobacco went into effect in late December. “California, We’ve Got You Covered,” the company declared in bold letters on a flier mailed to its cigarette customers.The law prohibits flavors, odors or “tastes” in tobacco products, including menthol cigarettes. But antismoking experts argue that R.J. Reynolds, the maker of Camel and Newport brands, is trying to circumvent the ban by luring smokers with a suite of what it says are new non-menthol versions offering “a taste that satisfies the senses” and “a new fresh twist.”The campaign is viewed by critics as a provocation of California authorities who are supposed to enforce the ban, which includes a provision outlawing packaging or claims that suggest a product has a flavor. The Food and Drug Administration also is moving forward with a national plan to take menthol cigarettes off the market.To public health authorities, the potential reduction in smoking rates from a menthol ban could extend the length and quality of millions of lives. To R.J. Reynolds and other tobacco companies, the loss of sales from menthol cigarettes could be financially damaging.Luis Pinto, the vice president of communications at R.J. Reynolds, said in an email that the “products introduced in California meet and comply with all applicable regulatory requirements.” He added that the new cigarettes “are not subject to the recently enacted ban because they do not have a distinguishable taste or aroma other than tobacco.”But while not all tobacco-control experts are certain that the new products violate the California law, they do agree that the Reynolds marketing campaign reflects decades-long efforts by tobacco companies to protest and flout government regulations.Dr. Robert Jackler, a professor at Stanford Medicine who provided the ads to The New York Times, called the new marketing “outrageous.”“The thing that surprises me is there’s no camouflage,” said Dr. Jackler, who received the mailers along with staff members of Stanford’s program on tobacco advertising. “They’re saying, ‘This is our menthol replacement. And by the way — wink, wink — it is not really menthol.’”A mailer collected from Camel by Dr. Jackler targeted Californians.via Robert JacklerThe tobacco flavor ban in California initially took shape as a law passed by the Legislature and signed by Gov. Gavin Newsom in 2020. Reynolds and others gathered signatures to let voters decide through a referendum on the issue. In November, 63 percent of voters approved the ban.In mid-December, the U.S. Supreme Court refused to block the law, rejecting a request by Reynolds. The company had cited “substantial financial losses” as a likely outcome of the ban, given that menthol cigarettes make up one-third of the cigarette market. The company had also noted that if the ban were to take effect, its customers “may never pledge the same brand loyalty.”More on Smoking, Vaping and E-CigarettesNew Zealand Ban: The country passed new laws aimed at preventing minors from becoming smokers, including a lifetime prohibition on cigarette sales to everyone born after 2008.California Ban: Antismoking experts are arguing that R.J. Reynolds is trying to circumvent California’s new ban on flavored tobacco with a suite of what it says are new non-menthol cigarettes offering “a taste that satisfies the senses.”Big Tobacco’s Contradictions: The industry seems to be embracing a healthier future with the rise of e-cigarettes, but it continues to fight laws and regulations aimed at curbing smoking.The Business of Addiction: McKinsey’s ties to opioid makers are well known, but for decades the consulting giant worked with Big Tobacco and has also advised Juul.The company had already sought to have the Supreme Court hear a separate appeal to the Los Angeles County flavor ban, which was passed in 2019.Bans on flavored tobacco products have been imposed in Massachusetts and dozens of cities and counties. Several states and numerous local authorities have outlawed flavored e-cigarettes. The California law also applies to vaping products.The California Department of Public Health said that it provided outreach to tobacco retailers on the law but that “enforcement is left to the local jurisdictions.” The Reynolds marketing campaign was earlier reported on the L.A. Taco news site.Menthol has been a major target for those who want to reduce smoking, since it infuses a cool, minty sensation that often appeals to young smokers and masks the harshness of tobacco. Studies have shown that the products have been marketed heavily to Black people.Carol McGruder, the co-chairwoman of the African American Tobacco Control Leadership Council and a supporter of the state law, said the new ads did not surprise her.“It’s racist, predatory marketing,” Ms. McGruder said. She added that public health officials were constantly having to react to the tobacco companies’ tactics, “as they try to stay alive — using addicted, lifelong customers.”Newport’s new, non-menthol cigarettes as advertised on its website.via Robert JacklerFliers for the new products were mailed to Reynolds’s customers who had sought coupons. They include ads for “new” Camel and Newport varieties with “bold, lasting flavor.” The company’s records of ingredients show that the Camel Crisp and the Newport EXP versions contain a synthetic cooling agent referred to as WS-3, according to Sven Jordt, a Duke University researcher who has written about the compound in e-cigarettes.Dr. Jordt said that the chemical had a cooling effect but not a minty odor or flavor, and that the health effects of the additive were unknown. While other countries have banned flavored tobacco or menthol, he said, only Germany and Belgium have prohibited this particular additive.Mr. Pinto, of Reynolds, said the cigarettes with the cooling agent “are not subject to the recently enacted ban because they do not have a distinguishable taste or aroma other than tobacco.”A spokesman for Altria, which sells Marlboro cigarettes, said the company had stopped selling menthol cigarettes in California and was in compliance with the new law.Worldwide, tobacco companies have discovered loopholes to bans on menthol or flavored tobacco, studies show. In Canada, flavor cards and additive drops have been used to supplement unflavored products. In Denmark, smokers now have access to menthol sprays, capsules and tubes.Drafters of the California law had the international experience in mind, by outlawing flavor accessories and any claims that promote a flavored product. To Dr. Pamela Ling, the director of the Center for Tobacco Control Research and Education at the University of California San Francisco, the message is clear.“If you squint at the ads, you’re going to see this as a flavorful product, whether it says it or not,” Dr. Ling said. “The colors, the packaging, the associations that your brain makes with the look and feel — that overrides the text that says this is not menthol.”A California tax stamp on the bottom of a pack of the new Newport cigarettes.Aaron Wojack for The New York TimesAdvertisements and packaging that so vividly suggest a flavor put a clear onus on California officials to respond to Reynolds, said Matt Myers, the president of the Campaign for Tobacco-Free Kids.“This is Reynolds basically challenging California to say, ‘I don’t think you’re serious,’” Mr. Myers said. If the state fails to take decisive action, he added, “the industry once again will escape.”The products being marketed as “new” also appear to challenge the authority of the F.D.A., according to Micah Berman, an associate professor of public health and law at Ohio State University. Under the Tobacco Control Act, products introduced after 2007 must be cleared by the agency, in part to keep tobacco companies from innovating to heighten the appeal of their products.“I think this is something the F.D.A. should go back and take a look at,” Mr. Berman said.Whether the products were cleared — and if they are “new,” as advertised — is difficult for F.D.A. officials to immediately determine. That’s because a 2016 legal defeat for the agency allows cigarette companies to change a product’s name without informing the F.D.A. To find out which cigarette is in a particular package, the agency typically investigates or inspects records in a manufacturing facility, said Mitch Zeller, the former director of the F.D.A.’s tobacco division.The agency cleared one Camel product with an “alternative menthol” flavor capsule in 2021. Reynolds declined to give The Times the authorization records for the California non-menthol cigarettes. Abigail Capobianco, a spokeswoman for the F.D.A., said that the agency closely monitored compliance with federal tobacco laws and regulations, and that it took corrective action when violations had occurred. But she declined to comment on the new products in California. The agency said it was finalizing its menthol rule and would “not allow entities to subvert the intent” of the product standard.California’s approach to the products will be an important bellwether of how a national menthol ban might play out, Dr. Ling said.Reynolds is “testing it out,” Dr. Ling said. “If they’re successful in pulling this off in California, they’ll be totally prepared to circumvent a federal ban everywhere else.”Adam Liptak

Published16 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Philippa RoxbyHealth reporterWomen’s experiences of care when giving birth have worsened in the last five years, says a report by England’s health and care regulator, the Care Quality Commission (CQC).A survey of 20,000 women found “a concerning decline” in getting help when most needed during labour and after childbirth.Overall satisfaction is high and mental health support in pregnancy is rising.The safety of maternity services has come under scrutiny in recent years.A BBC analysis recently showed that more than half of maternity units in England fail consistently to meet safety standards, with 48% requiring improvement and 7% posing a high risk of avoidable harm.A report from March 2022 into one hospital trust found that more than 200 babies might have survived if better maternity care had been given.The CQC asked thousands of women about their experience of giving birth in February 2022, and compared the results with previous years.From the responses, it found:78% definitely had confidence in staff involved during their labour and baby’s birth57% were always able to get a member of staff to help after childbirth – down from 62% in 201963% were able to get help when they needed it during labour and birth – down from 72% in 201923% said they were not taken seriously if they raised concerns during labour or birth – up from 19% in 201719% said they were not offered any choice about where to have their baby71% were always treated with kindness and understanding after the birth of their baby in hospital – down from 74% in 2017″These results show that far too many women feel their care could have been better,” said director of secondary and specialist care at the CQC, Victoria Vallance.She said it was vital for staff at individual trusts to understand what makes a good experience, and what needs to improve.But there was also recognition that the survey results reflected “increasing pressures on front-line staff” as they try to provide high-quality care with available resources.The CQC said a new programme of maternity inspections had recently begun in NHS hospitals across England which will have “a strong focus on capturing the experience of women and families”.’Unacceptable’Fewer than half of those who responded to the survey said their partners, or someone close to them, were able to stay with them when they were giving birth – compared with 74% before the pandemic.The National Childbirth Trust said this was “unacceptable”.”Trusts must immediately enable partners’ presence at in-hospital postnatal care so that mothers are never left without food and water, emotional support, access to a bathroom and help to lift and feed their baby,” chief executive Angela McConville said.The CQC report says mental health support during pregnancy and after childbirth is improving, with 96% of respondents saying a midwife or health visitor asked them about their state of mind after their baby was born.Areas for improvement include pregnant women’s concerns being taken more seriously during labour, more women being given advice and support at the start of their labour, and explanations of the care they need in hospital.”Maternity services in England are categorically falling short of women’s expectations,” Ms McConville said. “This is not all the impact of the Covid pandemic, but is directly associated with long-term underinvestment in the staffing of maternity services.”More on this storySafety failures too common in maternity units21 September 2022My role uncovering a shocking NHS maternity scandal2 April 2022Mothers who helped uncover the biggest NHS maternity scandal23 February 2022Nottingham maternity crisis: What do families want?31 August 2022Related Internet LinksNational survey of maternity experiences – Care Quality CommissionThe BBC is not responsible for the content of external sites.

In their laboratory at the Énergie Matériaux Télécommunications Research Centre of the Institut national de la recherche scientifique (INRS), Professor Jinyang Liang and his colleagues are developing a new ultrahigh-speed single-pixel camera. This new device, called single-pixel imaging accelerated via swept aggregate patterns (SPI-ASAP) is capable of streaming video at 12,000 frames per second using light modulation, giving it great flexibility. Published in the journal Nature Communications, this work represents a breakthrough in ultra-high-speed single-pixel imaging.
“This new camera is an innovative prototype with potential benefits for the photonics industry in Quebec and the rest of Canada,” says Dr. Liang, a researcher specializing in ultrafast imaging and biophotonics and the corresponding author of the study.
A powerful technology
For several years, Professor Jinyang Liang has focused his research on laser modulation techniques in new optical imaging devices. Single-pixel imaging (SPI) has emerged as a powerful technique using light modulation and a single-point detector instead of a two-dimensional sensor. However, most SPI systems are limited by the sole use of digital micromirror devices (DMDs) which means that the speed at which the single-pixel camera can record images is only a few tens of hertz.
Other methods use fast-moving physical encoding masks for light modulation. Although fast, these masks also fix the resolution, making such systems inflexible to be adapted to different experimental parameters.
In contrast to these approaches, the new camera developed by scientists at INRS combines a digital micromirror device with laser scanning for fast and reconfigurable pattern projection. This allows the system to operate at different spatial resolutions, as well as at different imaging speeds and modes. As a result, it is capable of streaming real-time video at 100 frames per second (fps), and up to 12,000 fps offline.
“The ability to image in real-time at 100 fps surpasses existing technologies and sheds light on many industrial applications where on-site analysis and online feedback are needed,” says Patrick Kilcullen, first author of the paper and a doctoral student at INRS.
Broad applications
Another feature is that the system is very generic and can be easily adapted to many configurations.
Scientifically, the device could have broad applications, especially in the non-visible spectrum, as there is no suitable camera. Very high-speed imaging allows the capture of transient events, such as the analysis of combustion phenomena, the detection of hazardous gases and the characterization of semiconductor materials.
The team, consisting of PhD student Patrick Kilcullen and professors Tsuneyuki Ozaki and Jinyang Liang, has patented the technique and is currently seeking collaborations to commercialize it.

Imperial researchers have developed a low-cost, easy-to-manufacture stabiliser for broken bones to help in regions where such devices are expensive or in short supply and people sometimes resort to homemade options.
The stabiliser, known as an external fixator, holds broken bones in place with metal pins or screws attached to a surrounding metal frame.
When soft tissue is severely damaged together with bone, external fixators are the first step in keeping fractures in legs and arms in place before an operation to definitively fix the bones can be carried out.
However, their cost and low availability in many regions mean people resort to homemade or low-quality fixators that may lead to serious complications or improper healing.
The Imperial external fixator is currently being tested in Gaza and Sri Lanka, and since the invasion of Ukraine, more than 500 fixators have been manufactured in Poland to help with the crisis.
This fixator, details of which are published in Frontiers in Medical Technology, is low-cost and has a lightweight design that can be manufactured locally to international standards. The team developed the design and a toolkit to allow repeated precise manufacture of the fixator anywhere in the world, including in the least developed countries.

In Sri Lanka, it is being tested for road traffic accidents, which account for around 70 percent of fractures in low- and middle-income countries (LMICs). In Ukraine and Gaza, both regions with unpredictable demand and supply of such devices, it is being used for gunshot wounds and other conflict trauma.
Lead researcher Dr Mehdi Saeidi, from the Department of Bioengineering at Imperial, said: “We have managed to develop an external fixator that is one-tenth of the cost of commercial devices but with similar performance. This device can provide surge capacity for conflict zones or in response to unpredictable incidents and situations, which was the case with the war in Ukraine.”
The fixator is made up of four clamping systems and a rod, which can be manufactured from stainless steel and aluminium, which are readily available materials, using conventional manufacturing techniques, such as milling and turning.
However, because of the precision of the parts, initial tests showed that the fixator would need to be built by highly skilled operators or using advanced machinery. Dr Saeidi therefore developed a manufacturing toolkit with components including drill bits, a saw and cutting guides to make the manufacturing easier, faster and reproducible with high accuracy.
The fixator was then tested in cadaver leg bones, showing it had similar stiffness to commercial devices, as well as undergoing mechanical testing that simulated pressure on the device to show its ability to keep the bones in position over a longer term.

The device is now being trialled in three countries. The device was originally conceived in response to a reported shortage by partners in Sri Lanka, and with Dr Puji Silva at the University of Moratuwa, the Imperial external fixator and related designs are being tested.
In Gaza, in collaboration with Professor Ghassan Abu-Sitt at the American University of Beirut, the device is largely being trialled with gunshot wounds. This trial is also assessing the ability of the external fixator to be cleaned, sterilised and reused.
Professor Abu-Sittah said: “In previous wars hospitals in Gaza had run out of external fixators, which jeopardised patient care. Developing the capacity to manufacture fixators locally means that this will not happen again.”
A second trial will soon start with the devices fully manufactured in Gaza, in collaboration with the Islamic University of Gaza (IUG). In preparation, Dr Saeidi trained Dr Sadiq Abdelall from IUG on manufacturing the external fixator using the toolkit at Imperial.
At the outbreak of the Ukraine conflict, Imperial’s Professor Anthony Bull was approached by surgeons in Poland who urgently needed such fixators, resulting in more than 500 of the devices being manufactured for use in Ukraine. The drawings provided freely on Imperial’s website were all that was needed by the engineers.
Professor Jonathan Jeffers, one of the study investigators from the Department of Mechanical Engineering at Imperial, said: “This work, conceived years ago based on needs identified by our military and civilian trauma surgeons, shows how basic engineering can mitigate suffering in the most dreadful of situations. The Ukraine situation is exactly why this project was conceived and demonstrates the ability to respond to surge demand.”
The team now expects to roll out the design to more LMICs at a larger scale with the help of partners in the World Health Organization and the United Nations Development Programme. The work was funded by the NIHR (project reference 16/137/45).

How cells shape complex tissues and organs during embryo development, which makes us what we are, has many mysteries.
New research from the University of Cincinnati has examined one such process which leads to the formation of vertebral column or spinal column. If this process is disrupted, it results in a birth defect called congenital scoliosis, or curvature of the spine. The UC research not only advanced understanding of how complex biological tissues form, but it could also lead to possible treatments for scoliosis in the future.
The research was published in the journal Nature.
“We are studying a basic science problem, the formation of the spinal column, the vertebral backbone that we all have,” says Ertuğrul Özbudak, PhD, professor in the Department of Pediatrics at the UC College of Medicine’s Division of Developmental Biology as well as Cincinnati Children’s Hospital Medical Center and lead author on the study. “By discovering the core mechanism governing it, we are able to reengineer this mechanism in mutant zebrafish which normally lack that process.”
Özbudak says in all vertebrate species, including humans, the spinal column is composed of segmented vertebral discs. Those discs that form the spine originate in embryonic blueprint segments called somites. As the embryo body elongates in all vertebrate species, it is cut into somites by a “biological clock knife.”
“As humans, we all pass through that knife-cutting process thanks to clock genes that express like blades,” says Özbudak. “There is a biological clock controlling this. Each time that clock ticks, the knife comes down and then separates the disc precursors, somites, from the others that will form later on.
“Some genes are part of this clock. When they are mutated, it results in scoliosis because there is no longer a knife that is cutting,” he adds. “By discovering this unknown hierarchy and imitating it with pharmaceutical drugs, we are able to now restore and reengineer that missing segmentation in the mutants which miss the molecular clock.”
Özbudak says the four UC students worked on the project and all contributed in different ways, bringing different skills and talents to the research. Chandel Angad Singh, a second-year doctoral student in the systems physiology graduate program, engineered a genetically modified animal model while Didar Saparov, a third-year doctoral student in the molecular and developmental biology graduate program at Cincinnati Children’s Hospital, conducted experiments with pharmaceutical drugs. Oriana Zinani, now a doctoral graduate from the molecular and developmental biologyB program, verified the precision of a genetic reporter fish for the molecular clock. Nick Clason, as an undergraduate co-op intern from the computer science department, contributed to the molecular simulations involved in the study.
“They had different backgrounds as undergraduates and they all did research in my lab,” Özbudak says of the students. “They formed a nice multidisciplinary team. In their bachelor’s degree [studies] Didar, Angad and Oriana majored in physics, biomedical engineering and biology, respectively. The team is led by Dr. Muhammed Simsek, a senior postdoctoral fellow in my lab at Cincinnati Children’s Hospital.”
Özbudak says the publication of the research has triggered positive responses from other scientists internationally.
“They are finding this study important and paradigm-shifting. We are hoping it will energize not only our lab members working on this project, but also several labs across the globe,” he says. “In a globalized society, hopefully everyone else will pitch in as well, and researchers from different countries and different universities will take these results and push them forward.
“Collectively, we will have a better understanding of why certain mutations cause diseases and we’ll understand the mechanisms behind it which will one day be helpful in curing congenital scoliosis.”

A new study by the University of Barcelona has analysed the viability of a new nanomolecule as drug delivery vehicle. The results, published in the journal Colloids and Surfaces B: Biointerfaces, show that liposomes designed by researchers are able to transport and deliver an anticancer drug that has been used as a model inside the cells. The study included the participation of researchers from the University of Barcelona faculties of Biology, Physics and Pharmacy and Food Sciences, as well as researchers from the Scientific and Technological Centers of the UB (CCiTUB), the Institute of Nanoscience and Nanotechnology of the UB (IN2UB) and from the Institute for Bioengineering of Catalonia (IBEC).
Interaction between liposomes and the cell membrane
A liposome is an artificial spherical vesicle with a membrane made of a dual layer of lipids which is similar to the structure of cell membranes. Since these molecules were found, in the sixties, they have been used as a model to study cell membranes and as a potential drug delivery system.
One of the challenges of turning liposomes into drug delivery vehicles is finding out how they interact with cell membranes and what basic mechanism — adsorption, fusion or endocytosis, or a combination of these three — is involved in the integration of liposomes by cells. “The interactions between liposomes and the cell membrane can be extremely different depending on the nature of the cell membrane and the lipidic composition of liposomes,” the researchers note.
The liposomes designed by the UB team are small lipid spheres with a composition similar to that of the cell they want to treat. “This similarity eases its incorporation and the drug delivery inside the cell,” notes Òscar Domenech, IN2UB member and one of the researchers that took part in the study.
Study in cell cultures
This study is the continuation of a previous study carried out by the same research team which analysed the fusion mechanisms of liposomes using a simplified model that copied the membrane of HeLa cells, a type of culture cells which are widely used in scientific research. “The membrane of HeLa cells is more complex than the model we used in the previous study. Now, we have used real cell cultures in order to obtain a better view of the interaction mechanism of our liposomes,” the researchers say.
To study the interaction between the liposomes and the cell membrane and to assess the integration of these nanomolecules, the researchers combined two techniques. On the one hand, they used confocal fluorescence, which allows them to see fluorescent molecules inside the cell. Then, the liposomes encapsulated calcein, a fluorescent dye, to see whether the nanomolecule and its content were entering the cells.
On the other hand, the researchers used the atomic force microscopy technique to see the physicochemical changes of the cell surface and assess the stiffness of the cell membrane in the presence of liposomes. The interaction of the liposomes designed by the researchers affirmed the results obtained with model membranes and it shows the capacity of the formulation of these nanomolecules as a potential nanotransporter. “We show that the lipid composition enables a delivery of the liposome content inside the cell, as well as the effect of the filopodia — small flagella of the cell — in easing the arrival of liposomes at the cell membrane,” adds Òscar Domènech.
A test with an anticancer drug
To validate the capacity of these liposomes as a drug delivery system, the researchers encapsulated methotrexate, an immunosuppressive drug used in the treatment of several oncologic, inflammatory and autoimmune pathologies. “We could show that our liposomes are ideal for delivering this model molecule, which we know can eliminate cancer cells,” notes Domènech.
These results open the door to future studies with other molecules and cell types. “Our interest would be to extend the methodology to other types of cells or even tissues to show the viability of the analysis, as well as to use other therapeutical molecules encapsulated in liposomes,” says Domènech. “Moreover — he adds — the two techniques we applied during the study allowed us to obtain results in a fast and minimally invasive way, which in the future could be indicators of the good functioning of a drug against cancer cells.”

Cambridge scientists have successfully trialled an artificial pancreas for use by patients living with type 2 diabetes. The device — powered by an algorithm developed at the University of Cambridge — doubled the amount of time patients were in the target range for glucose compared to standard treatment and halved the time spent experiencing high glucose levels.
Around 415 million people worldwide are estimated to be living with type 2 diabetes, which costs around $760 billion in annual global health expenditure. According to Diabetes UK, in the UK alone, more than 4.9million people have diabetes, of whom 90% have type 2 diabetes, and this is estimated to cost the NHS £10bn per year.
Type 2 diabetes causes levels of glucose — blood sugar — to become too high. Ordinarily, blood sugar levels are controlled by the release of insulin, but in type 2 diabetes insulin production is disrupted. Over time, this can cause serious problems including eye, kidney and nerve damage and heart disease.
The disease is usually managed through a combination of lifestyle changes — improved diet and more exercise, for example — and medication, with the aim of keeping glucose levels low.
Researchers from the Wellcome-MRC Institute of Metabolic Science at the University of Cambridge have developed an artificial pancreas that can help maintain healthy glucose levels. The device combines an off-the-shelf glucose monitor and insulin pump with an app developed by the team, known as CamAPS HX. This app is run by an algorithm that predicts how much insulin is required to maintain glucose levels in the target range.
The researchers have previously shown that an artificial pancreas run by a similar algorithm is effective for patients living with type 1 diabetes, from adults through to very young children. They have also successfully trialled the device in patients with type 2 diabetes who require kidney dialysis.

Today, in Nature Medicine, the team report the first trial of the device in a wider population living with type 2 diabetes (not requiring kidney dialysis). Unlike the artificial pancreas used for type 1 diabetes, this new version is a fully closed loop system — whereas patients with type 1 diabetes need to tell their artificial pancreas that they are about to eat to allow adjustment of insulin, for example, with this version they can leave the device to function entirely automatically.
The researchers recruited 26 patients from the Wolfson Diabetes and Endocrine Clinic at Addenbrooke’s Hospital, part of Cambridge University Hospitals NHS Foundation Trust, and a local group of GP surgeries. Patients were randomly allocated to one of two groups — the first group would trial the artificial pancreas for eight weeks and then switch to the standard therapy of multiple daily insulin injections; the second group would take this control therapy first and then switch to the artificial pancreas after eight weeks.
The team used several measures to assess how effectively the artificial pancreas worked. The first was the proportion of time that patients spent with their glucose levels within a target range of between 3.9 and 10.0mmol/L. On average, patients using the artificial pancreas spent two-thirds (66%) of their time within the target range — double that while on the control (32%).
A second measure was the proportion of time spent with glucose levels above 10.0mmol/L. Over time, high glucose levels raise the risk of potentially serious complications. Patients taking the control therapy spent two-thirds (67%) of their time with high glucose levels — this was halved to 33% when using the artificial pancreas.
Average glucose levels fell — from 12.6mmol/L when taking the control therapy to 9.2mmol/L while using the artificial pancreas.

The app also reduced levels of a molecule known as glycated haemoglobin, or HbA1c. Glycated haemoglobin develops when haemoglobin, a protein within red blood cells that carries oxygen throughout the body, joins with glucose in the blood, becoming ‘glycated’. By measuring HbA1c, clinicians are able to get an overall picture of what a person’s average blood sugar levels have been over a period of weeks or months. For people with diabetes, the higher the HbA1c, the greater the risk of developing diabetes-related complications. After the control therapy, average HbA1c levels were 8.7%, while after using the artificial pancreas they were 7.3%.
No patients experienced dangerously-low blood sugar levels (hypoglycaemia) during the study. One patient was admitted to hospital while using the artificial pancreas, due to an abscess at the site of the pump cannula.
Dr Charlotte Boughton from the Wellcome-MRC Institute of Metabolic Science at the University of Cambridge, who co-led the study, said: “Many people with type 2 diabetes struggle to manage their blood sugar levels using the currently available treatments, such as insulin injections. The artificial pancreas can provide a safe and effective approach to help them, and the technology is simple to use and can be implemented safely at home.”
Dr Aideen Daly, also from the Wellcome-MRC Institute of Metabolic Science, said: “One of the barriers to widespread use of insulin therapy has been concern over the risk of severe ‘hypos’ — dangerously low blood sugar levels. But we found that no patients on our trial experienced these and patients spent very little time with blood sugar levels lower than the target levels.”
Feedback from participants suggested that participants were happy to have their glucose levels controlled automatically by the system, and nine out of ten (89%) reported spending less time managing their diabetes overall. Users highlighted the elimination of the need for injections or fingerprick testing, and increased confidence in managing blood glucose as key benefits. Downsides included increased anxiety about the risk of hypoglycaemia, which the researchers say may reflect increased awareness and monitoring of glucose levels, and practical annoyances with wearing of devices.
The team now plan to carry out a much larger multicentre study to build on their findings and have submitted the device for regulatory approval with a view to making it commercially available for outpatients with type 2 diabetes.
The research was supported by the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre.

Severe inflammation weakens the body’s ability to kill cancerous blood cells in people with acute myeloid leukemia (AML), a new study shows.
Experiments in human cells also revealed how increasing levels of inflammation, marked by an aggressive reaction of immune cells in the bone marrow, altered the makeup of immune B cells and T cells needed to fight the disease like it would an invading bacteria or virus.
Using bone marrow samples of 20 adults and 22 children with the deadly disease, researchers at NYU Langone Health and its Perlmutter Cancer Center were able to score each patient’s level of inflammation. These “iScores” were then correlated to survival rates, with those having the lowest iScores typically surviving the longest. Leukemic patients with high iScores died at least four years earlier than those with low levels of inflammation.
The new “iScore” system can be added to existing tools for measuring AML severity and used by physicians and patients when deciding on immunotherapy, chemotherapy, or bone marrow transplantation, the NYU researchers say.
“Our scoring system provides an easy tool for physicians and patients to measure their risk from inflammation tied to their leukemia and to adjust their treatment plans accordingly to manage this risk,” says study co-lead investigator Audrey Lasry, PhD.
Measurements needed to calculate a patient’s iScore, she says, are freely available in the study manuscript to academic researchers and clinicians, and published in the journal Nature Cancer online Dec. 29, 2022.

Lasry, a postdoctoral fellow at NYU Grossman School of Medicine and Perlmutter Cancer Center, says some patients in consultation with their medical providers may favor immunotherapy to boost immune cells needed to fight cancer if their inflammation score is high. Others may favor alternative therapies in cases of low inflammation tied to their cancer because their immune system does not necessarily need reinforcement.
The study also showed that bone marrow levels of dysfunctional (atypical) immune B cells were also linked to inflammation in both adults and children with AML.
A dozen gene mutations, or errors in the genetic code, were found to be tied to high iScores and patients with severe cases of the disease.
Another key finding was that the effectiveness of some immune T cells, which directly attack cancer cells, was suppressed in child cases of leukemia with high inflammation but not in adult cases with high inflammation.
“Our study provides the first detailed description of how inflammation alters the tumor microenvironment in acute myeloid leukemia in both adults and children,” says study co-lead investigator Bettina Nadorp, PhD, also a postdoctoral fellow at NYU Grossman School of Medicine and Perlmutter Cancer Center.

“These study findings suggest that monitoring inflammation in patients with AML and possibly lowering inflammation levels with drug therapy should be considered as part of treatment for the disease,” says study senior investigator Iannis Aifantis, PhD.
Aifantis, the Hermann M. Biggs Professor and chair of the Department of Pathology at NYU Grossman and Perlmutter, says the team plans to analyze bone marrow samples from people with myelodysplastic syndrome, another blood cancer related to acute myeloid leukemia, to see if the same risk stratification applies based on inflammation.
For the investigation, researchers compared bone marrow samples from patients with acute myeloid leukemia to bone marrow samples from 10 healthy people who did not have cancer but were of similar age, race, and gender.
Some 246 genes tied to inflammation were found to be highly or less active in adults with the disease, while 187 genes linked to inflammation similarly stood out among children. By factoring in how long each patient lived with the disease, researchers narrowed their analysis to 38 relevant genes in adults and 11 in children and were then able to calculate a score that tied inflammation levels to survivability. When a number of patients’ iScores was compared, researchers say it is easy to see whose iScore is above or below average and by how much, information which can then be used to guide a patient’s treatment.
The research team has a patent application pending for the iScore for any commercial activity resulting from its use. The terms and conditions of this patent are being managed in accordance with the policies of NYU Langone.
Acute myeloid leukemia originates in the bone marrow and involves the buildup of abnormal blood cells, which can interfere with production of healthy blood cells. The common blood cancer occurs mostly in adults, resulting annually in the deaths of more than 11,500 Americans. Treatment options include chemotherapy, radiation, and immunotherapy. Bone marrow transplantation can also be considered if other options fail.
Funding support for the study was provided by National Institutes of Health grants P30CA016087, R01CA271455, R01CA173636, R01CA228135, R01CA242020, and R01HL159175. Additional funding support was provided by the Vogelstein Foundation, the Evans MDS Foundation, the American Lebanese Syrian Associated Charities, and the Aplastic Anemia and MDS International Foundation.
Besides Lasry, Nadorp, and Aifantis, other NYU Langone study investigators are Zhengxi Sun, Matthew Witkowski, Anastasia Tikhonova, Maria Guillamot-Ruano, Geraldine Cayanan, Anna Yeaton, Gabriel Robbins, Aristotellis Tsirigos, and William Carroll. Other researchers include Maarten Fornerod, at Erasmus Medical Center in Rotterdam, the Netherlands; Deedra Nicolet, Christopher Walker, and study co-senior investigator Ann-Kathrin Eisfeld, at The Ohio State University in Columbus; Huiyun Wu, Esther Obeng, and Stanley Pounds, at St. Jude Children’s Research Hospital in Memphis, Tenn.: Richard Stone, at Dana-Farber Cancer Institute, in Boston; John Byrd, at the University of Cincinnati in Ohio; and Tanja Gruber, at Stanford University in Palo Alto, Calif.