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Joint press release by Heidelberg University Hospital and the German Cancer Research Center

In a current paper published in the journal "Nature", Heidelberg-based researchers and physicians describe how neurons in the brain establish contact with aggressive glioblastomas and thus promote tumor growth / New tumor activation mechanism provides starting points for clinical trials

Neurons transmit their signals to each other via synapses, fine cell projections with terminals that contact another neuron. Researchers and physicians at Heidelberg University Hospital, Heidelberg Medical Faculty, and the German Cancer Research Center (DKFZ) have now discovered that neurons in the brain form these kinds of direct cell-to-cell contacts with tumor cells of aggressive glioblastomas too, thus transmitting impulses to the cancer cells. The tumor benefits from this "input": The activation signals are probably a driving force behind the tumor growth and the invasion of healthy brain tissue by tumor cells, as Frank Winkler, Thomas Kuner, and their teams discovered using special imaging methods. But there is also some good news: Certain substances can block the signal transmission in animal experiments. The results have just been published online in the journal "Nature".

Networks of neurons and tumor cells

Glioblastomas invade the healthy brain in a diffuse pattern like a fungal network. As a result, they cannot be completely removed by surgery, and they also survive intensive chemotherapy and radiotherapy. Glioblastomas are thus among the most dangerous tumors in humans; the average survival time is 15 months following the initial diagnosis.

In 2015, the team led by Frank Winkler, head of the Research Group Experimental Neurooncology in the Clinical Cooperation Unit Neurooncology, discovered a cause of this resistance to treatment: The glioblastoma cells are connected to one another through long cell protrusions. They communicate through these connections, exchange substances that are relevant for their survival, and thus protect themselves from treatment-related damage. The current findings add a further piece of the puzzle to our understanding of this type of cancer: "The tumor cells are not only interconnected in the brain like neurons; they also receive direct signals from them," explained Winkler, whose research group is affiliated with the University Hospital and the DKFZ.

The researchers observed the growth of human glioblastomas that they had transferred to mice, and studied cell cultures with human neurons and tumor cells, and tissue samples from patients. To do so, they used a wide range of modern microscopy methods, which provide detailed three-dimensional images of the connections - only micrometers large - between neurons and tumor cells as well as showing their molecular structure and signals within the cells. Electrical recordings from tumor cells revealed electrical currents generating from the synaptic connections, which form the starting point for further processing of these signals in the tumor cells. "We were able to show that signal transmission from neurons to tumor cells does in fact work like stimulating synapses between the neurons themselves," added Thomas Kuner, Director of the Department of Functional Neuroanatomy at the Institute for Anatomy and Cell Biology, where the synaptic connections were first discovered by Varun Venkataramani. "This project began with an observation in basic research. In close cooperation with our clinical partners, it has led to conceptually new insights which will allow new treatment approaches to be developed using targeted translational research."

A fatal mechanism - but one that opens up new avenues for treatment

How exactly activation of the tumor cell ultimately leads to increased tumor growth and invasion of healthy areas of the brain by the glioma cells has yet to be clarified. It is clear that this mechanism can be blocked in animals, however. Possible methods include a significant reduction of brain activity (for example under general anesthesia), pharmacological interventions that interrupt binding of the neurotransmitters on the AMPA receptor, or blocking the AMPA receptor using genetic engineering. In all these cases, tumor spread became slower in animal experiments. "This mechanism is therefore an extremely interesting approach for drug development and future drug treatments," neurooncologist Winkler emphasized. "Suitable substances have in fact already been approved that block the AMPA receptor and are used to treat other neurological diseases. These substances are promising candidates for clinical trials."

"The new results not only show what makes glioblastomas so aggressive, but also how they could be stopped. That is highly relevant from a translational point of view and paves the way for clinical studies," commented Wolfgang Wick, Medical Director of the Neurology Department at Heidelberg University Hospital and head of the Clinical Cooperation Unit Neurooncology at DKFZ. "We are also extremely pleased that the work of our junior researcher Varun Venkataramani, who also works in clinical practice, has been acknowledged by a publication in such a prestigious journal as ,Nature'."

The relevance of the results from Heidelberg has been confirmed by a paper from Stanford University, California, USA: Michelle Monje and her research team also found synaptic connections between neurons and tumor cells in currently untreatable pediatric brain tumors and also observed the treatment effects reported by the Heidelberg-based researchers. Both papers are being published in "Nature" simultaneously.

Satellite imagery from NASA-NOAA's Suomi NPP satellite showed Tropical Storm Kiko maintained its shape and strength after weakening from hurricane-force.

The Visible Infrared Imaging Radiometer Suite (VIIRS) instrument aboard Suomi NPP provided a visible image of Kiko on Sept. 18 at 5:36 p.m. EDT (2136 UTC) and revealed a circular area of powerful storms around the low-level center. The image showed strong bands of thunderstorms were located over the northern and southern quadrants of the storm. Those bands shifted location by the next day. On Sept. 19, the storm remained relatively compact with deep convection (strongest thunderstorms) organized in bands to the north and east of the low-level center.

Hurricanes are the most powerful weather event on Earth. NASA's expertise in space and scientific exploration contributes to essential services provided to the American people by other federal agencies, such as hurricane weather forecasting.

NOAA's National Hurricane Center or NHC said, "At 11 a.m. EDT (1500 UTC) the center of Tropical Storm Kiko was located near latitude 16.0 degrees north and longitude 128.7 degrees west. Kiko is far from land and centered about 1,310 miles (2,110 km) west-southwest of the southernmost tip of Baja California, Mexico. Kiko is moving toward the west near 6 mph (9 kph). Maximum sustained winds are near 65 mph (100 kph) with higher gusts.  Slow strengthening is forecast for the next few days, and Kiko may regain hurricane strength on Friday [Sept. 20]."

For updated forecasts. visit: http://www.nhc.noaa.gov

Humans choose food based on the way it looks, smells, and tastes. But the microbes in our guts use a different classification system--one that is based on the molecular components that make up different fibers. In a study published September 19 in the journal Cell, investigators found particular components of dietary fiber that encourage growth and metabolic action of beneficial microbes in the mouse gut.

The research aims to develop ways to identify compounds that can enhance the representation of health-promoting members of the gut microbial community. The goal is to identify sustainable, affordable dietary fiber sources for incorporation into next-generation, more nutritious food products.

"Fiber is understood to be beneficial. But fiber is actually a very complicated mixture of many different components," says senior author Jeffrey Gordon, a microbiologist at the Washington University School of Medicine in St. Louis. "Moreover, fibers from different plant sources that are processed in different ways during food manufacturing have different constituents. Unfortunately, we lack detailed knowledge of these differences and their biological significance. We do know that modern Western diets have low levels of fiber; this lack of fiber has been linked to loss of important members of the gut community and deleterious health effects."

The researchers started by testing 34 food-grade fiber preparations, many purified from byproducts of food manufacturing such as peels from fruits and vegetables that are thrown out during production of processed foods and drinks. They used mice initially raised under sterile conditions and then colonized with human gut microbes. The animals were fed a high-fat, low-fiber diet representative of diets typically consumed in the United States, with or without different types of supplemental fibers. The goal was to identify those fibers that were best at boosting the levels of key fiber-degrading bacterial species and promoting the expression of beneficial metabolic enzymes in the microbiome.

Since the mice had been colonized with a defined collection of human gut bacteria with sequenced genomes, the researchers knew all the genes that were present in their model human gut microbial community. This allowed them to perform a comprehensive, high-resolution proteomics study of all bacterial proteins whose expression changed in response to the different fiber types they tested. Combining these results with genetic screens, they were able to identify particular fiber sources, their bioactive molecular components, and the bacterial genes that increased for different Bacteroides species when they encountered different fibers. They focused on Bacteroides because members of this group of bacterial species contain genes responsible for metabolizing dietary fiber that are not present in the human genome.

For the second phase of the study, the investigators wanted to determine how different members of the microbial community interact with each other as they dine on dietary fiber. First author Michael Patnode, a postdoctoral fellow in Gordon's lab, developed fluorescently labeled artificial food particles with different types of bound carbohydrates from different fibers. Collections of these nutrient-containing particles were fed to mice colonized with defined microbial communities containing different combinations of Bacteroides species.

"We were excited to see how these 'biosensors' could be used to assess the processing of particular fiber components by particular bacterial species," Patnode says. By feeding these particles to mice that either carried or did not carry a dominant fiber-consuming species, the authors found that subordinate species were waiting in line to step up and consume the fiber.

"We had suspected there might be competition going on among the different strains and that some would be stronger competitors than others," Patnode says. Proteomics analyses and genetic screens confirmed that there was a hierarchy of fiber consumption among the species present in this model bacterial community.

Gordon explains that "it's important to understand how the presence of a particular organism affects the dining behavior of other organisms--in this case, with regard to different fibers. If we are going to develop microbiota-directed foods aimed at providing benefits to human health, it's important to find ways to determine which food staples will be the best source of nutrients and how the microbiota will respond."

Three of the world's foremost scientists will co-chair a commission of leading international experts to identify risks and develop a coherent suite of scientific targets to protect Earth's life support systems.

Johan Rockström, Joyeeta Gupta, and Dahe Qin will co-chair the Earth Commission, comprising an initial 19 members, announced today by the international research organisation Future Earth.

The group will begin immediately -- and complete by 2021 -- a high-level synthesis of scientific knowledge on the biophysical processes that regulate Earth's stability and targets to ensure this stability. The commission will also explore social transformations required for sustainable development to reach these targets.

The goal, ultimately, is to translate these into tangible science-based targets for Earth specifically tailored to cities and companies.

This translational work will be undertaken by a new Science Based Targets Network (SBTN) comprised of leading NGOs, enabling cities and companies to reduce their impact on and restore our oceans, freshwater, land, and biodiversity.

The aim is to make this standard practice in leading companies and cities by 2025.

"This year's fires in the Amazon, the rapidly warming Arctic, dying coral reefs, and unprecedented heat waves and floods across the world, are the clearest signals yet that human activities are pushing the planet further and further from the stable state we have enjoyed for 10,000 years," says Prof. Rockström, Director of the Potsdam Institute for Climate Impact Research and co-chair of Future Earth.

"To combat climate change, nations have agreed to limit global warming to well below 2 degrees," says Prof. Qin, director of the Academic Committee of Chinese Academy of Science.

"What we lack are comparable objectives for other key climate systems and environmental components that regulate the state of the Earth system and underpin sustainability-- water, land, food, biodiversity, chemicals, and others," adds Dr. Qin, also the Co-Chair of Working Group I of the Fourth and Fifth Intergovernmental Panel on Climate Change (IPCC) Assessment Reports.

"The Earth Commission will fill this critical gap, amassing the information needed to create science-based targets for these other essential parts of the Earth system," Dr. Qin adds.

The Earth Commission and the Science Based Targets Network are parts of the Global Commons Alliance, a network of organizations aiming to transform our economic systems to ensure our planet remains habitable. The alliance, launched in June, includes Earth HQ, a media portal for the planet, which will share the big picture of how Earth Systems are performing and tracking progress towards solutions.

"We will work closely with SBTN to ensure our analysis is useful and implementable, and how our analysis can provide guidance for development at, for example, a river basin scale," says Prof. Rockström.

Over 630 companies are already using science to commit how much and how quickly they need to reduce their greenhouse gas emissions through the Science Based Targets initiative (SBTi) set up in 2014.

The Earth Commission will build on and complement existing assessments, such as those conducted by the IPCC and Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES).

Dr. Gupta, Professor of Environment and Development in the Global South at the University of Amsterdam: "The UN Sustainable Development Goals are largely aspirational. The Commission's analysis will identify practical science-based targets that help realize these aspirations and deliver on Agenda 2030 to leave no one behind."

"The Earth Commission's work will also help inform intergovernmental treaty and/or policy negotiation processes such as those on biodiversity, desertification, and transboundary water," adds Dr. Gupta, who also co-chaired the recent UN Environment's Global Environmental Outlook-6.

The 19 commissioners include leading scientists in both natural and social sciences from 13 countries: Argentina, Australia (2), China (2), France, Germany (2), Ghana, India, Japan, Kenya, Netherlands (2), the United Kingdom, and the United States (4).

Certain human gut microbes with links to health thrive when fed specific types of ingredients in dietary fibers, according to a new study from Washington University School of Medicine in St. Louis.

The work -- conducted in mice colonized with human gut bacteria and using new technologies for measuring nutrient processing -- is a step toward developing more nutritious foods based on a strategy of targeted enrichment of key members of gut microbial communities. The researchers identified fibers that selectively increase the abundance of beneficial microbes and tracked down the bioactive components of fibers responsible for their effects. To decipher how members of gut communities compete or cooperate with each other for these fiber ingredients, they also invented a type of artificial food particle that acts as a biosensor for monitoring nutrient processing within the intestine.

The study appears Sept. 19 in the journal Cell.

"We are in the midst of a revolution in food science - where the naturally occurring molecules present in various food staples are being identified using advanced analytic tools," said senior author Jeffrey I. Gordon, MD, the Dr. Robert J. Glaser Distinguished University Professor, director of the Edison Family Center for Genome Sciences & Systems Biology and leader of the current study. "The resulting encyclopedias of food ingredients are providing an opportunity to understand how gut microbes are able to detect and transform these ingredients to products they use to satisfy their own needs, as well as share with us. Cracking the code of what dietary ingredients beneficial microbes covet is a key to designing foods that enhance health."

Dietary fiber is known to promote health, but typical Western diets are lacking in high-fiber fruits, vegetables, whole grains and legumes. Fibers contain very diverse and complex collections of molecules. The specific components of various fibers that are used by gut bacteria and confer health benefits are generally not known. Since the human genome possesses a very limited arsenal of genes that break down dietary fiber, and many gut bacterial species are chock full of these genes, people depend on gut microbes to digest fiber.

In an effort to understand which types of fiber promote the representation of different types of beneficial microbes in the human gut, and the nature of their active ingredients, the researchers screened 34 types of fiber provided by the food company Mondelez International. Their list included fibers often discarded during food manufacturing, such as fruit and vegetable peels and grain husks.

The researchers began by colonizing mice raised under sterile conditions with a collection of gut bacteria species they had cultured from a healthy human. The genomes of these organisms were sequenced to inventory their genes. Groups of mice containing this model human gut community initially were fed a base human diet high in saturated fats and low in fiber. Next, the researchers screened 144 derivative diets containing different types and amounts of fiber supplements. The investigators monitored the effects of the added fibers on levels of members of the model gut community, as well as expression of the proteins encoded by their genomes.

"Microbes are master teachers," Gordon said. "The microbial genes that respond to the different fibers provided an important clue as to what kinds of molecules in a given type of fiber a given community member preferred to consume."

Said first author Michael L. Patnode, PhD, a postdoctoral researcher in Gordon's lab: "Our screen identified food-grade fibers that selectively affected different species belonging to a group of bacteria known as Bacteroides. Our experiments showed that in pea fiber, the active molecular constituents included a type of polysaccharide called arabinan, whereas in citrus pectin recovered from orange peels, another type of polysaccharide called homogalacturonan was responsible for expansion of the bacteria."

The researchers uncovered interactions between gut bacterial species that help explain the selective effects of fibers on Bacteroides species. It turns out that some of the Bacteroides in their community directly compete with each other to consume components of dietary fibers, while others defer to their neighbors. Understanding these relationships is important for developing foods that are optimally processed by different microbial populations that live together in the gut, according to the researchers.

To dissect these relationships, Patnode created artificial food particles consisting of different types of magnetic, microscopic glass beads. Each type contained a given fiber-derived polysaccharide bound to the bead's surface together with a given type of bound fluorescent label. The collection of different bead types was introduced simultaneously into the intestines of different groups of mice colonized with the human gut microbial community -- with or without intentional omission of one or more of its Bacteroides members. Food particles then were recovered after passage through the intestines of these animals, and the amount of polysaccharide remaining on the particles surfaces was measured.

"These artificial food particles acted as biosensors, allowing us to decipher how inclusion or omission of Bacteroides influenced the community's ability to process the different polysaccharides present on the different beads," Patnode said. "Moreover, we were able to monitor fiber degradation in different diet contexts."

Gordon noted that nutrient-containing artificial food particles could not only be used as biosensors to define the functional capabilities of a person's microbial community, but also could help food scientists develop methods for producing more nutritious foods containing different combinations of health-promoting bioactive fiber components.

The answer to food insecurity could be as simple as a prescription for healthy food from your health care provider and the means to obtain it, particularly in food deserts, said researchers led by The University of Texas Health Science Center at Houston (UTHealth) School of Public Health.

The results will appear in the October issue of Translational Behavioral Medicine. Study partners included the Houston Food Bank, Harris County Public Health, and The University of Texas MD Anderson Cancer Center.

The two-year study focused on north Pasadena, Texas, where food insecurity is one of the highest in Harris County, said senior author Shreela V. Sharma, PhD, RD, professor of epidemiology, human genetics, and environmental sciences at UTHealth School of Public Health. First author was Jennifer N. Aiyer, MPH, RD, a doctoral student in epidemiology at the school.

People who are food insecure are also the ones struggling with chronic conditions such as obesity, diabetes, and high blood pressure, Sharma said.

"We want to catch them before they become sick," she said. "Those who are food insecure often eat unhealthy food."

The study was funded by the national BUILD Health Challenge through the Harris County BUILD Partnership, which aims to establish sustainable public sources of accessible healthy food in north Pasadena, develop a larger network of innovative food suppliers and distributors, and promote a healthy diet through the food prescription program. Study participants were recruited from two school-based clinics and one federally qualified health center.

"Many health care systems are now screening their patients for food security," Sharma said. "But there are challenges. What do you do when you find out they are food insecure?"

To answer that question, participants who were identified as food insecure at their clinics received a "food prescription" card from their providers that they could take to a designated food pantry located in north Pasadena every two weeks. They could receive as much as 30 pounds of fruits and vegetables and four forms of nonperishable foods such as lean protein, beans, and whole grains. The pantry resembled a small grocery store to reduce the stigma associated with going to a food pantry, and was stocked with food obtained from the Houston Food Bank.

Participants also received nutrition information, including books in English and Spanish, which discussed general nutrition, food storage and safety, and healthy recipes.

Of the 242 patients who opted to take part in the program, 172 (71.1%) redeemed the food prescription at the pantry at least once and of those who redeemed their prescriptions, 99% reported eating all or most of the fruits and vegetables. More than 94% felt that the produce helped them eat healthier.

"The biggest triumph is that the pantry continues to operate today," said Sharma. "Food insecurity stems from lack of access. The shift is providing access to healthy food and teaching people how to use it. That was the secret sauce to making this happen."

Such investments should last long-term with continuous access to healthy food and nutritional education, she said.

In experiments with mice and human tissue samples, Johns Hopkins Medicine researchers report evidence that neuronal stem cells in the part of the nose responsible for the sense of smell transform themselves to perpetuate the long-term inflammation in chronic sinusitis. Results of the study, they say, suggest that the stem cells' ability to switch their identity to join in the immune response may serve as a protective mechanism, while preserving the potential to regenerate the sense of smell tissue once the inflammation resolves.

In a report, which appears online Sept. 12 in the journal Cell Stem Cell, the scientists say the research also may advance the search for better treatments for the loss of smell that often accompanies chronic sinusitis.

More than just a stuffy nose, chronic sinusitis is marked by ongoing inflammation of the tissue lining the fluid-draining cavities of the skull and nose, resulting in congestion, thick mucus, and facial pain. The condition affects an estimated 30 million-40 million Americans and most lose their sense of smell to some degree. In a percentage, the sense of smell is completely lost, a troubling condition called anosmia. But how sinus inflammation affects the sense of smell has remained unclear.

For many, mucus and tissue swelling blockage alone can't explain why they lose their smell sense. "Losing this sense is a real disability," says Andrew Lane, M.D., professor of otolaryngology-head and neck surgery at the Johns Hopkins University School of Medicine. "People can't detect smells that warn them of impending danger, such as smoke, gas leaks or rotten food. Since most of the perceived flavor of food comes from smell, they lose their ability to taste, affecting their overall enjoyment of life."

Lane, an otolaryngologist whose practice focuses on treating people with sinus problems, says standard treatments with steroid pills to reduce inflammation don't always work, and come with side effects, such as bone weakness, change in vision, weight gain and vulnerability to infections. Topical steroids in nasal sprays and rinses can improve sinus congestion and other symptoms, he says, but frequently do not restore the sense of smell.

Neurons in the mucous membrane lining responsible for the sense of smell are called olfactory neurons, and they normally have a remarkable capacity for regeneration, says Lane, even when they are severely damaged by injury. However, in previous studies of a mouse model created by Lane and Johns Hopkins molecular biologist Randall Reed, Ph.D., they found that olfactory neurons damaged by chronic sinus and nasal inflammation fail to regenerate from olfactory stem cells known as horizontal basal cells.

To learn why such basal cells, with stem cell capabilities for regeneration, failed to regenerate olfactory neurons in cases of chronic sinusitis, Lane and postdoctoral fellow Mengfei Chen, Ph.D., studied tissue samples from people with chronic sinusitis and mice bred to develop olfactory inflammation, a model for chronic sinusitis in humans.

They sampled olfactory tissue from the mice early in the experiment, before extensive inflammation set in, and again six to eight weeks later.

The scientists sorted the cells in the olfactory tissue using a specific marker to isolate the olfactory horizontal basal cells. They found that late in inflammation, the basal cells became enlarged and increased in numbers, but shut down their regeneration capacity, meaning the basal cells did not form new neurons. After sequencing the cells' RNA, a genetic cousin to DNA and a measure of genetic output, the scientists discovered that the basal cells in the later stages of inflammation had undergone a transformation. They switched from having a preponderance of genes making proteins involved in dividing and becoming olfactory cells to doubling the expression of genes that make proteins involved in inflammation, including cytokines, which help immune cells communicate, and certain types of signaling proteins called chemokines, which attract immune cells known as macrophages and activate them.

In olfactory tissue samples from people with chronic sinusitis, the scientists found that basal cells increased in number and size and produced inflammatory cytokines, similar to the mouse model.

"What we have learned is that stem cells are not just passive receivers of signals instructing them to regenerate new neurons, but actually switch their identity to participate in the immune response," says Lane. "Our studies also show that as long as the inflammation persists, these cells stay in a stem cell state and don't revert to regenerating olfactory neurons."

One possible evolutionary explanation for not switching back, Lane says, is its critical protective function. "The real estate that these cells occupy so near to the brain is an important place to defend," says Lane. "The body doesn't want an infection or whatever else may be causing inflammation in the nearby sinuses to penetrate into the brain itself. So, rather than only serving to create more olfactory cells, it's likely these basal cells evolved to participate in the immune response as a last line of defense."

Lane says it's possible that chronic inflammation in other organs and parts of the body may prompt other adult stem cells to switch identities, slowing the renewal of tissue function.

A deeper understanding of how inflammation affects olfactory tissue and loss of smell-sensing neurons should help in the discovery of non-steroidal treatments that restore the sense of smell in people with chronic sinusitis, says Lane.

In addition to developing new drugs that protect neurons from injury or allow them to regenerate despite inflammation, the research may also help scientists understand why new treatments for inflammation currently on the market, such as dupilimab, which blocks protein pathways involved in asthma and sinus polyps, can restore the sense of smell in people with these conditions.

Dapagliflozin, a drug that is already used to successfully treat type 2 diabetes (T2D) and prevent development of heart failure, can also be used to treat pre-existing heart failure, even in patients without T2D.

These are the conclusions of research presented at this year's Annual Meeting of the European Association for the Study of Diabetes (EASD) in Barcelona, Spain (16-20 September), and simultaneously published in the New England Journal of Medicine (NEJM). The study is by Professor John McMurray, Professor of Cardiology at the Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK, and colleagues.

"The most important finding of all is the benefit in patients without diabetes," explains Professor McMurray. "This shows dapagliflozin is truly a treatment for heart failure and not just a drug for diabetes."

Heart failure occurs when the heart is no longer able to pump blood around the body as well as it should. In patients with heart failure, the percentage of blood pumped out by the left ventricle per heartbeat (called the ejection fraction) goes down. Certain conditions, such as coronary artery disease (narrowed arteries in the heart) or high blood pressure, gradually leave your heart too weak or stiff to fill and pump efficiently. The prevalence of heart failure in people with T2D is around double than in the general population without diabetes.

Dapagliflozin is one of the relatively new class of diabetes drugs called Sodium-glucose cotransporter 2 (SGLT-2) inhibitors. Previous studies have shown that SGLT-2 inhibitors not only help control blood sugar levels, but can also improve a number of cardiovascular outcomes, including promoting weight loss, reducing blood pressure and reducing the risk of cardiovascular mortality.

Dapagliflozin has already been proven to reduce the risk of developing heart failure in patients with type 2 diabetes. In this new study, the investigators analysed whether the drug could also be used to treat patients with T2D in whom heart failure had already developed (established heart failure), and also heart failure in patients without type 2 diabetes.

The trial (the DAPA-HF study) enrolled 4,744 patients with heart failure and reduced ejection fraction in 20 countries, of whom 45% had T2D, and 55% did not have T2D. Patients were randomly allocated to either dapagliflozin 10 mg once daily or matching placebo. The primary endpoint was a combination of a first episode of worsening heart failure (hospitalisation for heart failure or an urgent heart failure visit requiring intravenous therapy) or death from cardiovascular causes.

The treatments in the study were given on top of standard care: 94% received an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker or angiotensin receptor-neprilysin inhibitor; 96% took a beta-blocker; and 71% took a mineralocorticoid receptor antagonist (all these are drugs that reduce hospital admissions and death rates in heart failure, thus this new study was adding dapagliflozin or placebo to the currently best-available therapies).

The researchers found that, over a median follow-up of 18.2 months, the primary outcome occurred in 386 of 2,373 patients (16.3%) in the dapagliflozin group and in 502 of 2,371 patients (21.2%) in the placebo group, translating to a 26% reduced risk in the dapagliflozin (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.65-0.85; p

The components of the primary outcome were also analysed separately. A total of 237 patients (10.0%) receiving dapagliflozin and 326 patients (13.7%) receiving placebo experienced a first episode of worsening heart failure, thus showing a 30% reduced risk in the dapagliflozin group (HR 0.70; 95% CI 0.59-0.83; p

Regarding side effects, 178 patients (7.5%) in the dapagliflozin group had an adverse event related to volume depletion (which can cause dehydration, low blood pressure and fainting) compared to 162 (6.8%) in the placebo group, with no significant difference between groups. Adverse events related to kidney dysfunction occurred in 153 patients (6.5%) in the dapagliflozin group versus 170 patients (7.2%) in the placebo group, with no significant difference between groups. Major hypoglycaemia and lower limb amputation and fracture were infrequent and occurred at similar rates in the two treatment groups.

Professor McMurray says: "Adverse events rarely required the discontinuation of treatment. There was no notable excess of any serious adverse event in the dapagliflozin group."

He concludes: "The trial shows that dapagliflozin reduces death and hospitalisation, and improves health-related quality of life, in patients with heart failure and reduced ejection fraction, with and without diabetes. The clinical implications are potentially huge - few drugs achieve these results in heart failure and dapagliflozin does even when added to excellent standard therapy."

DGIST announced on Tuesday, September 10 that Dr. Jin-Kyu Kang's research team in Division of Energy Technology achieved 11.4% for the photoelectric conversion1 efficiency of flexible CZTSSe thin-film solar cell, the highest in the world. This research is expected to contribute to the development of future solar power technology and the thin-film solar cell industry of next generation.

Flexible thin-film solar cell can be applied in various fields such as wearable, building, and automobiles based on the flexible substrate technology. Since CZTSSe thin-film solar cell uses low-cost, ecofriendly materials, it is drawing limelight and is being researched as the next generation solar power technology throughout the world. However, Flexible CZTSSe`s photoelectric conversion efficiency had not exceeded 10% due to technological issue such as the spread of impurities inside the flexible substrate and delamination.

In response, the DGIST research team conducted research and achieved the highest efficiency of 11.4%, which was officially recognized. This achievement is drawing more attention because its mass production is much easier with the use of low-cost, ecofriendly materials such as copper(Cu), zinc(Zn), tin(Sn) than the existing thin-film solar cell (CIGS, CdTe, perovskite2), which uses high-cost heavy metal materials such as indium, lead, and cadmium.

One of the biggest achievements of this research is increased efficiency by changing the existing 3-stack structure of CZTSSe thin-film solar cell precursor into a multi-layered structure and by improving the voltage characteristics and uniformity. Moreover, it has the problem with uniformity degradation when a large-area process is applied to thin-film solar cell, but applied process technology in this research improved not only efficiency but also uniformity.

Dr. Kee-Jeong Yang who led the development of process technology said "Our research achievement has presented ways to secure the uniformity of large-area process, which can cause issues in commercialization. We will be able to advance the commercialization of next generation solar cell which is applicable in various fields such as building outer walls." Moreover, Senior Researcher Jin-Kyu Kang, the research project manager, said "As there is growing interest towards environment and resources are used unlimitedly these days, it is a very meaningful achievement that we have developed a thin-film solar cell using widely available, ecofriendly materials. We plan to lead the future solar cell technology using widely available materials and contribute to the development of thin-film solar cell industry.

Solar power offers a promising, renewable alternative to fossil fuels. But solar power production is complicated and influenced by ever-changing factors like cloud coverage, the time of day, and even dust particles in the air.

Professor Mahesh Bandi of Okinawa Institute of Science and Technology Graduate University (OIST) has co-developed a novel, standardized way of quantifying and comparing these variations in solar power. His new study, published in Physical Review Applied, may help guide the development and performance of solar photovoltaic farms - systems that harness the sun's energy and convert it to electricity.

"We currently have no standard to compare solar photovoltaic power fluctuations because they change depending on where they are measured," said Bandi, who works within OIST's Nonlinear and Non-equilibrium Physics Unit. "Finding that comparative basis is extremely important."

In Flux

Scientists use a quantity called the power spectrum to study fluctuations in solar photovoltaic power output - the energy that is generated when sunlight is converted to electricity.

Scientists can use the power spectrum to quantify the magnitude of fluctuations in the power generated by individual solar plants across the planet. However, there is no standard against which to compare these distinct values across plants because the readings vary based on features like cloud coverage and dust in the air. Just as the gold standard was used to value currency in the 19th and 20th centuries, a standard measurement is necessary to meaningfully assess energy production across plants.

To identify such a standard, Bandi and his collaborator, Professor Golan Bel of Ben Gurion University of the Negev in Israel, analyzed the clear-sky index, which quantifies the sun's energy output as electromagnetic waves, without any interference from clouds or dust.

The researchers' analysis of clear-sky data from 2009 revealed that this basic solar irradiance followed a pattern that depended on changes in daylight duration from one day to another.

Bandi and Bel concluded that measuring the basic solar radiation at a specific location on Earth forms a reliable standard of comparison for the photovoltaic power spectrum at the same location. This is because, even despite the variability of clouds and other sources of noise, geographic location reliably impacts photovoltaic power production.

Bandi's next step is to study how sources of noise like passing clouds impacts fluctuations in solar power. Ultimately, he hopes this research can inform engineering and policy to optimize photovoltaic power production.

"We have crossed the first barrier in understanding the character of solar photovoltaic fluctuations by finding this gold standard," said Bandi. "We now have a ruler to measure with."

New research has shown how parental engagement has a positive effect on a child's academic attainment - regardless of age or socio-economic status.

The study, conducted by the Universities of Plymouth and Exeter, also highlighted areas of promise for how schools and early years settings can support parents in a way that improves their children's learning.

The work was commissioned by the Education Endowment Foundation and supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South West Peninsula (PenCLAHRC).

The report showed that for school-aged children, home-school partnership is hugely important - especially where schools personalise communications about a child's progress and make them accessible, for example, through text messages.

The study also highlighted how family literacy interventions can help to boost younger children's learning, and how summer reading programmes can improve school-aged children's learning, particularly among families from more disadvantaged backgrounds.

The researchers made their conclusions by conducting a review of existing international studies on the links between parental engagement and students' learning, and comparing the findings with survey responses from head teachers in over 180 primary, secondary and early-years provisions across England. They also conducted 20 interviews with school leaders and subject experts to provide further context and explore the survey findings in more detail.

As well as the links between parental involvement and children's learning, the study explored activities delivered in or by schools and early years settings that promote and support parental engagement, particularly for children from disadvantaged backgrounds.

The school-wide survey showed that the majority of the 183 schools involved (72%) did not have a written policy in place around engagement applied to all parents/carers, but most respondents (80%) did consider parent engagement to be the responsibility of all staff.

Lead author Dr Nick Axford, PenCLAHRC Associate Professor in Health Services at the University of Plymouth, explained that there was no one thing that schools should do to support parent engagement, but that there were areas showing promise.

"These findings from existing studies and new surveys are interesting, because they highlight the positive link between parental engagement and children's academic attainment," he said.

"However, it takes time and planning to nurture and encourage parent support. Recommendations we would put forward include for schools to build parental engagement into their school improvement plans, and to work hard on establishing good communication with parents. The latter could even involve training and support for teachers on engaging with parents, especially as very little is provided to promote this within teacher training."

Dr Vashti Berry, PenCLAHRC Senior Research Fellow at the University of Exeter, said: "We recognise that schools and early years settings are working in a challenging financial climate, and that much more research on how best to support parents is needed. But school leaders recognise the importance of working with parents, and there are lots of practical suggestions in the Education Endowment Foundation guide that is based on our report, so there is fertile ground for improvement."

Dr Jenny Lloyd, Senior Lecturer in Public Health at the University of Exeter, said: "School staff recognise that engaging parents in children's learning requires the building of supportive and trusting relationships from the foundation stage all the way through to the end of secondary education. Schools need resources, systems and structures to create a continuity of care and education that involves parents."

New Rochelle, NY, September 19, 2019-Mast cells are critically involved in immunity and immune disorders. However, they are rarely cultured ex vivo for experimental manipulation because of the difficulty in isolating useful numbers and limitations related to 2D culture. A new study reports the successful development of authenticated mast cells by culturing hematopoietic stem cells in an engineered 3D connective tissue matrix. The work is published in Tissue Engineering, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here to read the article for free on the Tissue Engineering website through October 19, 2019.

Heather Gappa-Fahlenkamp, PhD, School of Chemical Engineering, Oklahoma State University, OK, with other colleagues from OSU present their work in an article titled "Human Mast Cell Development from Hematopoietic Stem Cells in a Connective Tissue-Equivalent Model." In an attempt to recapitulate the native environment, the authors isolated mast cell progenitors and co-cultured them with human primary fibroblasts in a 3D collagen matrix; the matrix was then coated with type IV collagen and fibronectin, and endothelial cells were seeded to stimulate further mast cell development. Several characteristics of cell morphology and phenotypic marker expression were assessed to validate typical mast cell immune-related behavior, demonstrating the success of this technique.

"The authors present a successful complex tissue model for studying mast cell progenitors and mast cell development," says Tissue Engineering Co-Editor-in-Chief Antonios G. Mikos, PhD, Louis Calder Professor at Rice University, Houston, TX. "Not only will this model prove useful in understanding mast cell biology, but it may also be a rich testing ground for future therapies and drug discovery involving mast cells, inflammatory disorders, and allergic diseases."

ROCHESTER, Minn. -- In a small safety and feasibility clinical trial, Mayo Clinic researchers have demonstrated for the first time that senescent cells can be removed from the body using drugs termed "senolytics". The result was verified not only in analysis of blood but also in changes in skin and fat tissue senescent cell abundance. The findings appear in the journal EBioMedicine.

This trial -- involving participants who had diabetes-related kidney disease -- is the second clinical study of senolytics to be published by Mayo, but is the first trial to show that senolytic drugs, discovered by Mayo researchers, can remove senescent cells from humans as they did in numerous studies in animals.

Senescent cells are malfunctioning cells that accumulate with aging and in organs affected by chronic diseases. Senescent cells can remain in the body and contribute to multiple diseases as well as features of aging, ranging from heart disease to frailty, dementias, osteoporosis, diabetes, and kidney, liver, and lung diseases.

"Senescent cells can develop in all mammals in response to disease, injury, or cancerous mutations. Senolytic drugs do not interfere with generation of senescent cells, which could lead to cancer. However, once formed, senescent cells can contribute to developing cancers, multiple other diseases, and consequences of aging," says James Kirkland, M.D., Ph.D., senior author and head of the Robert and Arlene Kogod Center on Aging.

"By targeting senescent cells with senolytics in mice, we can delay, prevent, or treat multiple diseases and increase health and independence during remaining years of life," says Dr. Kirkland. "As we increase our understanding of these drugs and their effects, we hope there may be benefits for a range of human diseases and disorders."

For three days the nine participants received a combination dose of dasatinab and quercetin. Though the drugs cleared the body in a couple of days, effects on reducing senescent cells were evident for at least 11 days. The researchers say this shows the senolytic drug combination significantly decreases senescent cell burden in humans. Senescent cells are characteristic in end-stage kidney failure as well as diabetes-related kidney disease. By removing the cells from mice, researchers had previously found that senolytics alleviate insulin resistance, cell dysfunction, and other processes that cause disease progression and complications.

While more research is needed on the impact of senolytics on diseases and disorders of aging, the researchers say the results of occasional dosing reduces risks from having to give drugs continuously.

"This small-scale clinical trial is a significant step forward for translation of senolytic therapies," says Ronald Kohanski, Ph.D., deputy director, Division of Aging Biology, National Institute of Aging. "The demonstration that senescent cell numbers can be reduced in two tissues in humans is an important advance based on the compelling evidence from studies in laboratory mice."

Women who give birth to singleton babies following assisted reproductive technologies including vitro fertilisation (IVF) are at greater risk of developing gestational diabetes than those who conceive naturally, according to a meta-analysis involving over almost 2 million singleton pregnancies.

The analysis, being presented at this year's European Association for the Study of Diabetes (EASD) Annual Meeting in Barcelona, Spain (16-20 September), found a 53% increased risk of gestational diabetes in women who became pregnant via assisted reproduction techniques (4,776/63,760 women) compared with spontaneous conception (158,526/1,870,734).*

More than 8 million babies have been born from assisted reproduction technologies around the world since the first IVF baby in 1978. Estimates suggest that more than half a million babies are now born each year from IVF and intracytoplasmic sperm injection (ICSI)--a procedure in which a single sperm cell is injected directly into an egg, rather than fertilisation happening in a dish, as in standard IVF [1].

Pregnancies achieved by assisted reproduction are associated with more obstetric and perinatal complications, such as pre-eclampsia, placental anomalies, caesarean sections, early delivery, and low birthweight, compared with pregnancies achieved by natural conception, even among singleton births. But whether assisted reproduction technologies are linked with gestational diabetes is unclear and previous studies have yielded contradictory results.

In this study, Dr Panagiotis Anagnostis from the Aristotle University of Thessaloniki in Greece and colleagues did a systematic review and meta-analysis of cross-sectional studies, comparing the risk of gestational diabetes in singleton pregnancies achieved by IVF and ICSI and spontaneous conception up to July 2019.

Analysis of data from 38 studies (17 matched controls and 21 unmatched), involving nearly 2 million women and 163,302 cases of gestational diabetes, found that women who gave birth to singleton babies following assisted reproduction were 53% more likely to develop gestational diabetes than those who conceived naturally.

Further analysis of 17 studies (involving 21,606 women) in which women were matched for age, height, weight, smoking status, and ethnic origin indicated that women who underwent assisted reproduction techniques were 42% more likely to develop gestational diabetes compared with spontaneous conception.

"This rigorous assessment of the best available evidence to date shows that singleton pregnancies achieved by IVF are linked with an increased risk of developing gestational diabetes compared with pregnancies conceived naturally", says Dr Anagnostis. "The exact mechanism is unclear, and whether this risk is due to the medical intervention or the underlying infertility status of the couples undergoing assisted reproduction, is not yet fully understood and requires further research."

He adds: "Whilst gestational diabetes remains a rare outcome for assisted reproduction technologies, the complications of the former indicate that women at risk must be identified and monitored, ensuring they receive early detection and appropriate support and care."

As this is a meta-analysis of observational studies, no firm conclusions can be drawn about cause and effect, and the authors point to several limitations including that most studies did not adjust for important confounders.

Previous research has shown that people born weighing 2.7 kg (6 lbs) or less face an increased risk of developing type 2 diabetes (T2D) as adults. New research being presented at this year's European Association for the Study of Diabetes (EASD) Annual Meeting in Barcelona, Spain (16-20 September) is the first study to show that babies born underweight are more likely to develop type 2 diabetes at a younger age (by more than one year) and have less severe obesity at the time of diabetes diagnosis with higher concentrations of HDL cholesterol (known as good cholesterol).

"Our observational study of more than 48,000 births is important as it shows, for the first time, that irrespective of other clinical factors such as sex, body-mass index, and cholesterol levels at diagnosis, a low birthweight is associated with increased susceptibility to type 2 diabetes at a younger age", says Mr Christian Paulina, a medical student from the University of Dundee, UK who conducted the research.

"This link between low birthweight and age of onset of diabetes may reflect common genetic factors that both mediate birthweight and diabetes risk, or intrauterine factors such as nutrition or maternal smoking, or the combination of the two."

While the link between low birthweight and risk of developing type 2 diabetes in later life is well established, its association with the phenotype (physical characteristics) of type 2 diabetes once it develops is less clear cut.

In this study, researchers from the University of Dundee linked more than 48,000 individuals enrolled in the Walker Birth Cohort who were born in Dundee, Scotland between 1952 and 1966 to Scotland's national diabetes registry. They then investigated the impact of low birthweight on the phenotype of type 2 diabetes at diagnosis including age at diagnosis, body mass index [BMI], creatinine [a marker of kidney function], serum alanine aminotransferase [ALT; an enzyme that reflects liver function], HDL cholesterol, triglycerides [type of fat in the blood], and systolic blood pressure.

They found that compared with a baby born weighing over 3.6kg (the top 25% of birthweights in the cohort), being born with a low birthweight (

Further analyses showed that the effect of birthweight on age of diabetes diagnosis was not influenced by other clinical factors suggesting that low birthweight affects the risk of developing type 2 diabetes in the same way irrespective of your BMI and HDL cholesterol, in adulthood.

Researchers also found that whilst men had a slower progression to insulin treatment, birthweight (standardised for gestational age and sex) did not have a significant impact on diabetes progression.

While measures of insulin production were not available, the authors conclude that the mechanism linking low birthweight to younger onset slimmer patients with type 2 diabetes may be connect to reduced insulin secretion--both in the womb and later life.