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An article, written with other vaccine experts, put the regulators at odds with key federal health officials, including Dr. Anthony S. Fauci.WASHINGTON — Two departing Food and Drug Administration regulators argued in a review published Monday that none of the data on coronavirus vaccines so far provided credible evidence in support of booster shots for the general population. Their assertion revealed significant disagreement between career scientists at the agency and top Biden health officials, who have already started planning a broad booster campaign for this fall.The review, published in The Lancet, was written by an international group of vaccine experts including Dr. Philip Krause and Marion Gruber, longtime F.D.A. scientists who recently announced that they would leave the agency. It comes days before an advisory committee is to publicly discuss and vote on whether the F.D.A. should approve additional doses of Pfizer-BioNTech’s vaccine for people 16 and up.Dr. Krause and Dr. Gruber, who lead the F.D.A.’s vaccine office and have regulated vaccines for decades, were not writing on behalf of the agency; the article stated that “opinions expressed are those of the authors, and do not necessarily represent the opinions of their respective organizations.” Still, the arguments they put forth suggested that regulators might raise objections to Pfizer’s application for approval of a booster dose at the advisory panel meeting, scheduled for Friday.An F.D.A. spokeswoman emphasized that “the views of the authors do not represent the views of the agency,” adding: “We are in the middle of a deliberative process of reviewing Pfizer’s booster shot supplemental approval submission, and F.D.A. as a matter of practice does not comment on pending matters before the agency. We look forward to a robust and transparent discussion on Friday about that application.”Dr. Gruber and Dr. Krause were said to have disagreed with the Biden administration’s push for boosters before federal scientists could review all the evidence and make recommendations, a conflict that factored into their decisions to depart this fall. The two are likely to be crucial to any decisions the agency makes about boosters; Dr. Gruber would be expected to formally sign off on them.But other top F.D.A. officials, including Dr. Janet Woodcock, the acting agency commissioner, and Dr. Peter Marks, a career regulator who oversees the vaccine office that Dr. Gruber and Dr. Krause lead, could overrule them.The publication of the Lancet article raised questions about whether Dr. Woodcock, who signed on to the Biden administration’s booster announcement last month, had consulted Dr. Gruber or other career experts in the F.D.A. vaccine office before advising the administration and making clear her own position on the issue. Some public health experts said Dr. Woodcock’s endorsement of the plan boxed in her regulators.The Biden administration announced in August a proposal to begin administering vaccine boosters eight months after people’s second shots, contingent on authorization from the F.D.A. and a recommendation from the Centers for Disease Control and Prevention. And the pandemic plan that Mr. Biden announced last week included booster-shot readiness, stating, “A booster promises to give Americans their highest level of protection yet.”But many scientists have opposed the plan, saying the vaccines continue to be powerfully protective against severe illness and hospitalization. The authors of the Lancet article included a compendium of dozens of studies from around the world that shows such a trend.Federal health officials have said that one reason they announced the booster plan was to stay ahead of the virus and be ready for when vaccines may no longer protect as well against severe cases of Covid-19. Those officials, including Dr. Anthony S. Fauci, Mr. Biden’s chief medical adviser, have relied heavily on data presented to them by Israeli officials, who have defended that country’s early, aggressive booster campaign.Their data, Dr. Fauci and other administration officials have said, show a clear waning of immunity against infection, with enhanced protection from booster doses, but show only hints of waning immunity against hospitalization in people under 65.But in the new review, Dr. Krause, Dr. Gruber and other vaccine experts said that more time and public discussion, and better studies, were needed to determine if boosters were needed for the general population. They also said that whatever advantage the shots might provide would not outweigh the benefit of using them to protect the billions of people who remain unvaccinated worldwide. The World Health Organization has asked wealthy countries to hold off on administering extra shots to healthy patients until at least the end of the year as a way of enabling every country to vaccinate at least 40 percent of its population. Every unvaccinated person provides an opportunity for the virus to morph into new, potentially dangerous, variants, scientists have warned.The review authors did, however, say that extra shots might be useful for some people with weak immune systems — a step the F.D.A. already authorized.“As more information becomes available, it may first provide evidence that boosting is needed in some subpopulations,” they wrote. “However, these high-stakes decisions should be based on peer-reviewed and publicly available data and robust international scientific discussion.”They were largely dismissive of the Israeli data and other studies that some health officials have said make the case for imminent extra shots. They said some Israeli evidence was collected just a week or so after the third dose and might not hold up over time, and that “a very short-term protective effect would not necessarily imply worthwhile long-term benefit.”They also said that a reduction in vaccine efficacy against mild cases of Covid-19 did not necessarily mean there would be a drop in efficacy against severe disease..css-1xzcza9{list-style-type:disc;padding-inline-start:1em;}.css-3btd0c{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:1rem;line-height:1.375rem;color:#333;margin-bottom:0.78125rem;}@media (min-width:740px){.css-3btd0c{font-size:1.0625rem;line-height:1.5rem;margin-bottom:0.9375rem;}}.css-3btd0c strong{font-weight:600;}.css-3btd0c em{font-style:italic;}.css-w739ur{margin:0 auto 5px;font-family:nyt-franklin,helvetica,arial,sans-serif;font-weight:700;font-size:1.125rem;line-height:1.3125rem;color:#121212;}#NYT_BELOW_MAIN_CONTENT_REGION .css-w739ur{font-family:nyt-cheltenham,georgia,’times new 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a:hover{-webkit-text-decoration:none;text-decoration:none;}“To date, none of these studies has provided credible evidence of substantially declining protection against severe disease,” they wrote, “even when there appear to be declines over time in vaccine efficacy against symptomatic disease.”The authors also said that countries with a lot of vaccinated people would inevitably see some breakthrough cases, especially if the vaccinated start taking more risks.Several studies published by the C.D.C., including three on Friday, suggest that while efficacy against infection with the Delta variant seems to wane slightly over time, the vaccines hold steady against severe illness in almost all age groups. Only in adults over 75 do the vaccines show some weakening in protection against hospitalization.Immunity conferred by vaccines relies on protection both from antibodies and from immune cells. Although the levels of antibodies may wane and raise the risk of infection, the body’s memory of the virus is long-lived.The vaccines are slightly less effective against infection with the Delta variant than with the Alpha variant, but the virus has not evolved to evade the sustained responses from immune cells, the experts said. Boosters may eventually be needed even for the general population if a variant emerges that sidesteps the immune response, they added.The experts cautioned that promoting boosters before they are needed, as well as any reports of booster side effects such as heart problems or Guillain-Barré syndrome, might undermine confidence in the primary vaccination. They wrote that because booster doses have been shown to induce strong responses, lower doses might be adequate and safer. They also emphasized that tweaking the vaccines to specifically protect against new variants, like Delta, might be the best and longest-lasting approach, in part because new variants would be likely to evolve from those in highest circulation. Moderna and Pfizer are both evaluating Delta-specific booster shots.The F.D.A. is still gathering data on all three vaccines used in the United States, and it will be at least several weeks before regulators can decide whether people who received the Moderna or Johnson & Johnson vaccines might need another dose. Starting boosters for recipients of only one vaccine could confuse the public, the authors said.“Booster programs that affect some but not all vaccinees may be difficult to implement — so it will be important to base recommendations on complete data about all vaccines available in a country, to consider the logistics of vaccination, and to develop clear public health messaging before boosting is widely recommended,” the authors wrote.

Statistics from the Centers for Disease Control and Prevention (CDC) show that obesity affects more than 40% of American adults, placing them at higher risk for heart disease, stroke, type 2 diabetes, and certain types of cancer. The USDA’s Dietary Guidelines for Americans 2020 — 2025 further tells us that losing weight “requires adults to reduce the number of calories they get from foods and beverages and increase the amount expended through physical activity.”
This approach to weight management is based on the century-old energy balance model which states that weight gain is caused by consuming more energy than we expend. In today’s world, surrounded by highly palatable, heavily marketed, cheap processed foods, it’s easy for people to eat more calories than they need, an imbalance that is further exacerbated by today’s sedentary lifestyles. By this thinking, overeating, coupled with insufficient physical activity, is driving the obesity epidemic. On the other hand, despite decades of public health messaging exhorting people to eat less and exercise more, rates of obesity and obesity-related diseases have steadily risen.
The authors of “The Carbohydrate-Insulin Model: A Physiological Perspective on the Obesity Pandemic,” a perspective published in The American Journal of Clinical Nutrition, point to fundamental flaws in the energy balance model, arguing that an alternate model, the carbohydrate-insulin model, better explains obesity and weight gain. Moreover, the carbohydrate-insulin model points the way to more effective, long-lasting weight management strategies.
According to lead author Dr. David Ludwig, Endocrinologist at Boston Children’s Hospital and Professor at Harvard Medical School, the energy balance model doesn’t help us understand the biological causes of weight gain: “During a growth spurt, for instance, adolescents may increase food intake by 1,000 calories a day. But does their overeating cause the growth spurt or does the growth spurt cause the adolescent to get hungry and overeat?”
In contrast to the energy balance model, the carbohydrate-insulin model makes a bold claim: overeating isn’t the main cause of obesity. Instead, the carbohydrate-insulin model lays much of the blame for the current obesity epidemic on modern dietary patterns characterized by excessive consumption of foods with a high glycemic load: in particular, processed, rapidly digestible carbohydrates. These foods cause hormonal responses that fundamentally change our metabolism, driving fat storage, weight gain, and obesity.
When we eat highly processed carbohydrates, the body increases insulin secretion and suppresses glucagon secretion. This, in turn, signals fat cells to store more calories, leaving fewer calories available to fuel muscles and other metabolically active tissues. The brain perceives that the body isn’t getting enough energy, which, in turn, leads to feelings of hunger. In addition, metabolism may slow down in the body’s attempt to conserve fuel. Thus, we tend to remain hungry, even as we continue to gain excess fat.
To understand the obesity epidemic, we need to consider not only how much we’re eating, but also how the foods we eat affect our hormones and metabolism. With its assertion that all calories are alike to the body, the energy balance model misses this critical piece of the puzzle.
While the carbohydrate-insulin model is not new — its origins date to the early 1900s — The American Journal of Clinical Nutrition perspective is the most comprehensive formulation of this model to date, authored by a team of 17 internationally recognized scientists, clinical researchers, and public health experts. Collectively, they have summarized the growing body of evidence in support of the carbohydrate-insulin model. Moreover, the authors have identified a series of testable hypotheses that distinguish the two models to guide future research.
Adoption of the carbohydrate-insulin model over the energy-balance model has radical implications for weight management and obesity treatment. Rather than urge people to eat less, a strategy which usually doesn’t work in the long run, the carbohydrate-insulin model suggests another path that focuses more on what we eat. According to Dr. Ludwig, “reducing consumption of the rapidly digestible carbohydrates that flooded the food supply during the low-fat diet era lessens the underlying drive to store body fat. As a result, people may lose weight with less hunger and struggle.”
The authors acknowledge that further research is needed to conclusively test both models and, perhaps, to generate new models that better fit the evidence. Toward this end, they call for constructive discourse and “collaborations among scientists with diverse viewpoints to test predictions in rigorous and unbiased research.”

Adults with normal blood pressure and high levels of stress hormones were more likely to develop high blood pressure and experience cardiovascular events compared to those who had lower stress hormone levels, according to new research published today in Hypertension, an American Heart Association journal.
Studies have shown that cumulative exposure to daily stressors and exposure to traumatic stress can increase cardiovascular disease risk. A growing body of research refers to the mind-heart-body connection, which suggests a person’s mind can positively or negatively affect cardiovascular health, cardiovascular risk factors and risk for cardiovascular disease events, as well as cardiovascular prognosis over time.
“The stress hormones norepinephrine, epinephrine, dopamine and cortisol can increase with stress from life events, work, relationships, finances and more. And we confirmed that stress is a key factor contributing to the risk of hypertension and cardiovascular events,” said study author Kosuke Inoue, M.D., Ph.D., assistant professor of social epidemiology at Kyoto University in Kyoto, Japan. Inoue also is affiliated with the department of epidemiology at the Fielding School of Public Health at the University of California, Los Angeles.
“Previous research focused on the relationship between stress hormone levels and hypertension or cardiovascular events in patients with existing hypertension. However, studies looking at adults without hypertension were lacking,” Inoue said. “It is important to examine the impact of stress on adults in the general population because it provides new information about whether routine measurement of stress hormones needs to be considered to prevent hypertension and CVD events.”
Study subjects were part of the MESA Stress 1 study, a substudy of the Multi-Ethnic Study of Atherosclerosis (MESA), a large study of atherosclerosis risk factors among more than 6,000 men and women from six U.S. communities. As part of MESA exams 3 and 4 (conducted between July 2004 and October 2006), white, Black and Hispanic participants with normal blood pressure from the New York and Los Angeles sites were invited to participate in the substudy MESA Stress 1. In this substudy, researchers analyzed levels of norepinephrine, epinephrine, dopamine and cortisol — hormones that respond to stress levels. Hormone levels were measured in a 12-hour overnight urine test. The substudy included 412 adults ages 48 to 87 years. About half were female, 54% were Hispanic, 22% were Black and 24% were white.
Participants were followed for three more visits (between September 2005 and June 2018) for development of hypertension and cardiovascular events such as chest pain, the need for an artery-opening procedure, or having a heart attack or stroke.

A new study led by scientists at Sanford Burnham Prebys has shown that the protein RNF5 plays an unusual role in acute myeloid leukemia (AML). Unlike its expected role, marking aberrant proteins for destruction, RNF5 binds with a second cell protein called RBBP4 to control expression of genes implicated in AML. These findings, published in Nature Communications, have important implications for improving AML patient outcomes.
“AML cells are highly dependent on the RNF5 protein,” says Ze’ev Ronai Ph.D., director of the NCI-designated Cancer Center at Sanford Burnham Prebys and senior author of the paper. “If we inhibit it, AML cells don’t survive. We can also use RNF5 levels to stratify patients for specific treatments. For example, if AML patients have low levels of RNF5 or RBBP4, they respond better to HDAC inhibitors, which are targeted treatments already used in the clinic.”
The Ronai lab has been studying RNF5 for about ten years, mostly in breast and skin cancers, and became curious about its role in AML because AML patients with high RNF5 levels often have poor outcomes. In this study, the Ronai lab worked closely with clinicians at Scripps MD Anderson in La Jolla, the Rambam Health Care Campus in Israel and other leading scientists to generate the findings.
Normally, as a ubiquitin ligase, RNF5 helps mark other proteins for destruction. But this research found that RNF5 picks up a different skill in AML cells, partnering with the epigenetic regulator RBBP4. Rather than degrading it, RNF5 modifies RBBP4 such that it impacts its recruitment to control expression of genes associated with AML growth.
“It was quite surprising for us to find this ubiquitin ligase is actually regulating gene transcription in AML,” says Ali Khateb, Ph.D., a postdoctoral researcher in the Ronai lab and first author on the paper. “Ubiquitination improves recruitment of this epigenetic regulator to target genes. When you don’t have RNF5 in the cells, there is less recruitment of RBBP4 to the target genes, leading to their increased expression — and this inhibits AML growth.”
The team continued to accumulate evidence that RNF5 and RBBP4 work together to drive AML. By analyzing patients’ samples from the U.S. and Israel, they confirmed that patients with high RNF5 levels have poor prognosis. They also showed that animals injected with cells that are inhibited for RNF5 have a delay in leukemia development and longer survival. Further work showed that inhibiting RBBP4 produced the same results.
These findings could have several therapeutic ramifications. Inhibiting RNF5 could make existing targeted therapies more effective. “We found that when RNF5 or RBBP4 are inhibited, AML cells become super sensitive to HDAC inhibitors,” says Khateb.
“Patients with lower levels of either RNF5 or RBBP4 will probably respond better to HDAC inhibitors,” says Ronai. “We may be able to identify which AML patients will respond to these treatments based on their RNF5 or RBBP4 expression.”
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Researchers at Umeå University, Sweden, now demonstrate a method by which specific cell types in human organs can be studied with micrometer precision. The method can be used to reveal previously unrecognised alterations in the pancreas, but it can also be used to study other human organs and diseases.
“This method may contribute to an advanced understanding of how cellular changes are related to different disease conditions,” says Ulf Ahlgren, Professor of molecular medicine at Umeå University.
What the researchers have done is to divide the organs by the use of a 3D-printed matrix, creating portions of tissue with the optimal size for optical imaging using 3D technology. These pieces can then be labelled to visualize essentially any cell type or protein of choice. Since each bit of tissue has known coordinates, the individual 3D images can be pieced together using a computer into a three-dimensional jigsaw puzzle to form an intact human organ.
This method makes it possible to create high-resolution 3D images of human organs in practically any size, with maintained micrometer precision — which is smaller than a dust particle. Previously, it has been possible to create high-resolution images of biological material with the use of technology such as optical projection tomography and light sheet fluorescence microscopy, which is something the researchers have used also in this study. Instead, the problem has been that previous methods have offered no usable way of labelling the various cell types or proteins you wish to study, for instance using fluorescent antibodies, when you are studying specimen on a larger scale, such as an entire organ. This is the problem that the new method has now solved.
The Umeå researchers have used the method to study the human pancreas. Inside the pancreas, you will find hundreds of thousands of insulin-producing cells called the Islets of Langerhans. These islets hold a key function in the production of insulin and are hence a key element in diabetes when the production is disturbed. Using this new method, the researchers are able to demonstrate previously unrecognised features of the human pancreatic anatomy and pathology, including areas with extremely high islet density. Their results may have implications for anything from preclinical to clinical areas, for instance to improve islet transplantation protocols for people with diabetes, or when developing non-invasive clinical imaging to study the pancreas in people with diabetes.
“Beside using the new method to study diabetes, it can also improve understanding of other pancreatic diseases, not least pancreatic cancers, and we have initiated collaborations with clinical researchers in Umeå to look into that. But the technology itself should be possible to use to study other organs and diseases in similar ways since it enables the study of where cellular changes take place in a full organ context, their amount and relationship to nearby tissues and cell types” says Ulf Ahlgren.
The published study was performed in collaboration with researchers at Uppsala University and was funded by the Swedish Research Council, the Swedish Childhood Diabetes Foundation, Diabetes Wellness Sverige, the NovoNordisk Foundation, the Kempe Foundations and Umeå University. The study was published in the journal Communications Biology.
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Materials provided by Umea University. Original written by Ola Nilsson. Note: Content may be edited for style and length.

A Cleveland Clinic study has introduced a new surgical procedure to treat both children and adults with congenital intestinal malrotation, an inherited disorder that can cause the intestines to twist.
The study, published in the Annals of Surgery, also defines the disease presentation in both children and adults, identifies the patients at risk of intestinal loss, and assesses the long-term outcomes after different surgical interventions.
Congenital intestinal malrotation, also known as gut malrotation, can cause the small and large intestines to twist, which potentially can lead to the development of life-threatening complications. The condition, often overlooked or misdiagnosed, can affect people at any age.
Malrotation occurs in about one out of every 500 births in the United States. During pregnancy, a baby’s bowel normally rotates 270-degree counterclockwise and then becomes fixed in position. With gut malrotation, however, this embryonic process is defective and sometimes associated with mal-development of the gut, abdominal wall and the nerve supply of the intestine. As a result, babies, children and adults with the disorder can suffer from several gastrointestinal symptoms — from abdominal pain, nausea and bloating to food intolerance and altered bowel habits. Most seriously, twisted intestines — known as volvulus — often result in loss of most of the small bowel and half of the colon with the need for long-term intravenous nutrition. Some patients may ultimately need life-saving intestinal or multivisceral transplantation.
Drawing on 30 years of experience in digestive surgery and transplantation, Kareem Abu-Elmagd, M.D., Ph.D. — director of Cleveland Clinic’s Center for Gut Rehabilitation and Transplantation and lead author of the study — developed a new gut malrotation correction surgery to alleviate the gastrointestinal symptoms as well as prevent the need for gut transplantation. “During the procedure, the digestive organs are rearranged and fixed in their proper anatomic locations, which prevents the intestines from twisting and resolves the digestive symptoms with improved quality of life,” said Dr. Abu-Elmagd.
The operation that has been used traditionally to address intestinal malrotation is called the Ladd’s procedure, which untwists the intestines and alleviates the bowel obstruction by dividing adhesive bands between the duodenum (upper part of the small intestine) and colon.

The human body is made of numerous different types of cells, which have small compartments known as organelles to perform complex biochemical reactions. These compartments have multiple enzymes that work together to execute important cellular functions. Researchers at the Center for Soft and Living Matter within the Institute for Basic Science (IBS, South Korea) have successfully mimicked these nano spatial compartments to create ‘artificial mitochondria’ in the latest research published in Nature Catalysis as a cover article. They state the technology can be used to construct artificial organelles that can supply ATP or other useful molecules to cells in damaged or diseased tissues.
This was achieved through reprogramming of ‘exosomes’, which are small vesicles (diameter ~120 nm) that cells use for intercellular signaling. The researchers carried out the experiments using microfluidic droplet reactors, which generated small droplets that were of similar size as typical cells. (diameter ~10 nm) The researchers first aimed to facilitate controlled fusion of these exosomes within the droplets while preventing unwanted fusions.
They accomplished this by tailoring the exosome surfaces with molecules called catechol, which is a chelating agent that forms complexes with metal ions. This was in turn done by attaching the catechol onto antibodies that target specific cell markers, such as CD9. The complex-forming property of catechol allows them to drive fusions between exosomes when they are mixed with metal ions such as Fe3+. The membrane fusion occurs when the catechols on the surfaces bind to the iron and bring the vesicles to close proximity to one another.
Researchers first tested the effectiveness of this system by loading one type of exosomes with calcein-Co2+ and another with EDTA. When the two vesicles fuse and the contents are mixed, EDTA grabs the Co2+ away from calcein, which then allows the latter to fluoresce. The team realized they were successful upon the detection of the fluorescence signal, and the fusion was further confirmed by the doubling of the measured exosome diameter.
These customized exosomes were then preloaded with different reactants and enzymes, which turned them into biomimetic nano factories. This allows them to produce high-value biomolecules by performing desired biocatalytic transformations in a spatially confined manner which is not possible using conventional laboratory test tubes. The team demonstrated this multienzyme biocatalytic cascade function by encapsulating glucose oxidase (GOx) and horseradish peroxidase (HRP) inside the exosomes. The GOx first converts glucose into gluconic acid and hydrogen peroxide. The HRP in turn uses the hydrogen peroxide generated in the first reaction to oxidize Amplex Red to a fluorescent product, resorufin. The researchers were even able to take a step further by adding a third enzyme, galactosidase which converts lactose into glucose, into the mix.
Next, the researchers wanted to know exactly how well these mini reactors can be uptaken and internalized by the cells. The cells derived from human breast tissues were fed with fused exosome nanoreactors, and their internalization over the next 48 hours was observed using various markers and a confocal laser scanning microscope (CLSM). It was found that cells were able to uptake these customized exosomes primarily through endocytosis, along with multiple other mechanisms. They further tested the beforementioned GOx-HRP two enzyme system in the cells, and it was found that the fused exosomes were able to successfully manufacture fluorescent products even while being inside the cells.
Armed with this knowledge, the team sought to create functional artificial mitochondria that are capable of producing energy inside the cells. To achieve this, ATP synthase and bo3 oxidase were reconstituted into the earlier exosomes containing GOx and HRP, respectively. These exosomes were in turn fused to create nanoreactors that can produce ATP using glucose and dithiothreitol (DTT). It was found that the fused exosomes were capable of penetrating deep into the core part of a solid spheroid tissue and produce ATP in its hypoxic environment. The activities of these simple organelles were accompanied by marked reduction of reactive oxygen species (ROS) generation. In contrast, free enzymes were unable to penetrate inside these tightly packed spheroids of cells.
“Taken together, our results highlight the potential of these exosomes as nanoreactors in regulating the metabolic activity of cells inside spheroids, and in attenuating cell damage due to hypoxia,” notes CHO Yoon-Kyoung, the corresponding author of the study. It is hoped that further research into such artificial organelles will present a new paradigm in various fields such as disease diagnosis and treatment, biotechnology, medicine, and the environment.
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MIT engineers, in collaboration with scientists at Cancer Research UK Manchester Institute, have developed a new way to grow tiny replicas of the pancreas, using either healthy or cancerous pancreatic cells. Their new models could help researchers develop and test potential drugs for pancreatic cancer, which is currently one of the most difficult types of cancer to treat.
Using a specialized gel that mimics the extracellular environment surrounding the pancreas, the researchers were able to grow pancreatic “organoids,” allowing them to study the important interactions between pancreatic tumors and their environment. Unlike some of the gels now used to grow tissue, the new MIT gel is completely synthetic, easy to assemble and can be produced with a consistent composition every time.
“The issue of reproducibility is a major one,” says Linda Griffith, the School of Engineering Professor of Teaching Innovation and a professor of biological engineering and mechanical engineering. “The research community has been looking for ways to do more methodical cultures of these kinds of organoids, and especially to control the microenvironment.”
The researchers have also shown that their new gel can be used to grow other types of tissue, including intestinal and endometrial tissue.
Griffith and Claus Jorgensen, a group leader at the Cancer Research UK Manchester Institute, are the senior authors of the paper, which appears today in Nature Materials. The lead author is Christopher Below, a former graduate student at the Cancer Research UK Manchester Institute.
Mimicking the microenvironment
Traditionally, labs have used commercially available tissue-derived gel to grow organoids in a lab dish. However, as the most widely used commercial gel is a complex mixture of proteins, proteoglycans, and growth factors derived from a tumor grown in mice, it is variable from lot to lot and has undesirable components present, Griffith says. It also doesn’t always allow for growth of multiple types of cells. About 10 years ago, Griffith’s lab started to work on designing a synthetic gel that could be used to grow epithelial cells, which form the sheets that line most organs, along with other supportive cells.

Researchers at Children’s Hospital of Philadelphia (CHOP) have demonstrated that an experimental device can improve blood sugar control in patients who developed diabetes after their pancreas was removed to treat their hyperinsulinism, a genetic disease in which the pancreas produces too much insulin. Using a combination of continuous glucose monitoring, two hormone pumps, and an algorithm, the device, known as the bihormonal bionic pancreas (BHBP) and developed by researchers at Boston University, helped HI patients with diabetes maintain stable glucose levels over the study period.
The findings were published today in Diabetes Care.
“Managing glucose levels in patients with HI and post-pancreatectomy diabetes is extremely challenging because they have residual insulin that is highly dysregulated, so they often fluctuate between low blood sugar and high blood sugar,” said Diva D. De León-Crutchlow, MD, Chief of the Division of Endocrinology and Diabetes and Director of the Congenital Hyperinsulinism Center at Children’s Hospital of Philadelphia. “Our study shows that the bihormonal bionic pancreas offers glycemic control to these patients without the risk of human error in calculating doses.”
Congenital HI is a genetic disorder in which the insulin cells of the pancreas, called beta cells, secrete too much insulin. Because insulin helps shuttle glucose from the blood into the cells, excess insulin causes low blood sugar, or hypoglycemia, a dangerous condition that can lead to seizures, brain damage and possibly death. Although approximately 50% of children with the condition respond to medical therapy, the other half require surgery for a partial or near total removal of their pancreas. Doing so leads to post-pancreatectomy diabetes (PPD) and dysregulated production of glucagon, a hormone formed in the pancreas which promotes the breakdown of glycogen to glucose in the liver.
Currently, HI treatment after the removal of the pancreas involves waiting until the hypoglycemia associated with HI tips over to hyperglycemia due to the lack of insulin. At that point, the patients can be treated with small amounts of insulin, the levels of which must be calculated by a caregiver. However, that approach involves a delay in care, and given the swings between hypo- and hyperglycemia, the proper calculation of dosage and timing can be stressful for families.
Instead, researchers from CHOP, Massachusetts General Hospital, and Boston University investigated the use of the bihormonal bionic pancreas (BHBP) in HI patients, so that treatment could occur sooner and administered more quickly. The BHBP works by autonomously administering insulin and glucagon based on plasma glucose levels detected by a continuous glucose monitor (CGM); an algorithm calculates the exact dosage based on the CGM measurements.
The researchers enrolled 10 patients with HI and PPD. The patients spent two periods of three nights each using two methods of blood glucose control: one period using their own insulin pump, and one using the BHBP. Although the differences between the two periods were not large due to small sample size, the results showed a trend towards an overall improvement of blood sugar control in the BHBP period relative to the period in which patients used their own insulin pumps. The patients in the study had varying levels of control of their blood glucose levels at the start of the study, but all patients were able to keep their levels in the appropriate range during the BHBP period. None of the patients experienced severe hypoglycemia during the BHBP period.
“Given the promising results of this pilot study, larger and longer studies using the newer BHBP device in this population to establish the long-term benefit and risks of the BHBP should be pursued,” Dr. De León-Crutchlow said.
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Findings of a nationwide study led by the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, suggest that a family’s socio-economic status (SES) may influence children’s composition of gut microbiome — the mix of microscopic organisms within the digestive tract.
SES includes economic resources such as education, income and occupation, and are reflected in living conditions, nutrition and psychosocial stress, according to the study, which focused on the education levels of mothers and fathers.
Samples of DNA and nucleic acids from a racially diverse group of 588 children, ages 1 month to 15 years old, found that environmental factors such as SES could influence the health of individuals throughout their lives, potentially influencing such measures as blood pressure, height, weight, diabetes, obesity and even attention-deficit/hyperactivity disorder (ADHD). Gut microbiota play an important role in a broad range of body functions, including the immune system, metabolic and inflammatory processes, and the central nervous system.
While previous studies have examined how SES can affect the gut microbiome of adults, this is one of the first such examinations in young children, according to the study published recently in the journal Microorganisms.
“These findings may have important implications for understanding how interventions in childhood could help prevent the eventual impact of SES on microbiome diversity and subsequent health,” said Candace Lewis, Ph.D., a post-doctoral fellow in TGen’s Neurogenomics Division, and the study’s lead author. “Our results demonstrate that modifiable environmental factors, such as SES, may influence gut microbiome composition at an early age.”
Human DNA samples were collected from saliva. Microbial nucleic acid samples were extracted from stool. Investigators tested and ranked for an abundance of gut microbes, including: Anaerostipes, Bacteroides, Eubacterium, Faecalibacterium, and Lachnospiraceae. Parents with more years of education had children who scored higher on a “latent microbiome factor,” defined as higher abundance of Anaerostipes, Eubacterium, Faecalibacterium, and Lachnospiraceae, and lower abundance of Bacteroides.
Faecalibacterium, considered a key biomarker of a healthy gut, produces butyrate, which is an energy source that plays a major role in gut physiology and has several beneficial health effects, including protection against pathogens, modulation of the immune system, and reduction of cancer progression.
“Faecalibacterium abundance may be one biological pathway in which early environmental influences shape disease vulnerability through life,” the study said.
Other factors considered in the study were age, sex, antibiotic exposure, and even birth type (whether the child was born vaginally or by caesarean section).
“These results are important, as our understanding of gut microbiome influences on health continue to expand,” said Sarah Highlander, Ph.D., a Research Professor in TGen’s Pathogen and Microbiome Division and one of the study’s authors. “This study tests the associations between family SES with the relative abundance of microbiota type and diversity of infants and children, while controlling for potential genetic associations.”
Contributing to this study were: Arizona State University; Wellesley College; Hasbro Children’s Hospital; Brown University; and Maternal, Newborn & Child Health Discovery & Tools, a part of the Bill and Melinda Gates Foundation.
Funding for this study — Family SES Is Associated with the Gut Microbiome in Infants and Children — was provided by: National Institutes of Health (NIH), the NIH’s Environmental Influences on Child Health Outcomes (ECHO project), and the NIH’s National Institute of Child Health and Human Development.