Culture

MSA toolkits first appear some 300 thousand years ago, at the same time as the earliest fossils of Homo sapiens, and are still in use 30 thousand years ago. However, from 67 thousand years ago, changes in stone tool production indicate a marked shift in behaviour; the new toolkits that emerge are labelled LSA and remained in use into the recent past. A growing body of evidence suggests that the transition from MSA to LSA was not a linear process, but occurred at different times in different places. Understanding this process is important to examine what drives cultural innovation and creativity, and what explains this critical behavioural change. Defining differences between the MSA and LSA is an important step towards this goal.

"Eastern Africa is a key region to examine this major cultural change, not only because it hosts some of the youngest MSA sites and some of the oldest LSA sites, but also because the large number of well excavated and dated sites make it ideal for research using quantitative methods," says Dr. Jimbob Blinkhorn, an archaeologist from the Pan African Evolution Research Group, Max Planck Institute for the Science of Human History and the Centre for Quaternary Research, Department of Geography, Royal Holloway. "This enabled us to pull together a substantial database of changing patterns of stone tool production and use, spanning 130 to 12 thousand years ago, to examine the MSA-LSA transition."

The study examines the presence or absence of 16 alternate tool types across 92 stone tool assemblages, but rather than focusing on them individually, emphasis is placed on the constellations of tool forms that frequently occur together.

"We've employed an Artificial Neural Network (ANN) approach to train and test models that differentiate LSA assemblages from MSA assemblages, as well as examining chronological differences between older (130-71 thousand years ago) and younger (71-28 thousand years ago) MSA assemblages with a 94% success rate," says Dr. Matt Grove, an archaeologist at the University of Liverpool.

Artificial Neural Networks (ANNs) are computer models intended to mimic the salient features of information processing in the brain. Like the brain, their considerable processing power arises not from the complexity of any single unit but from the action of many simple units acting in parallel. Despite the widespread use of ANNs today, applications in archaeological research remain limited.

"ANNs have sometimes been described as a 'black box' approach, as even when they are highly successful, it may not always be clear exactly why," says Grove. "We employed a simulation approach that breaks open this black box to understand which inputs have a significant impact on the results. This enabled us to identify how patterns of stone tool assemblage composition vary between the MSA and LSA, and we hope this demonstrates how such methods can be used more widely in archaeological research in the future."

"The results of our study show that MSA and LSA assemblages can be differentiated based on the constellation of artefact types found within an assemblage alone," Blinkhorn adds. "The combined occurrence of backed pieces, blade and bipolar technologies together with the combined absence of core tools, Levallois flake technology, point technology and scrapers robustly identifies LSA assemblages, with the opposite pattern identifying MSA assemblages. Significantly, this provides quantified support to qualitative differences noted by earlier researchers that key typological changes do occur with this cultural transition."

The team plans to expand the use of these methods to dig deeper into different regional trajectories of cultural change in the African Stone Age. "The approach we've employed offers a powerful toolkit to examine the categories we use to describe the archaeological record and to help us examine and explain cultural change amongst our ancestors," says Blinkhorn.

In a development that may finally offer hope to children with Dravet syndrome and their parents, a promising investigational new therapeutic appears to alter the destructive course of the deadly disease in a mouse model.

Lori Isom, Ph.D., Chair of the U-M Department of Pharmacology and Professor of Molecular & Integrative Physiology, and Neurology and her team have spent several years tracing the developmental pathway of Dravet syndrome, a debilitating genetic disease that causes intractable seizures and can lead to sudden death. Dravet syndrome variants lead to a decrease in the level of a crucial protein that normal brain cells use to control the flow of sodium ions into cells. Neurons use these sodium channels to transmit signals back and forth.

Patients with Dravet syndrome have variants in a sodium channel gene, SCN1A, that in general result in there being only half the amount of the corresponding functional protein, Nav1.1, expressed in the brain. "With only 50 percent SCN1A expression in the brain, you have a severe epileptic disease with a high risk of sudden death," Isom says.

The team's goal was to increase the gene's expression back up to 100 percent in neurons using an antisense oligonucleotide (ASO) that was developed by Stoke Therapeutics, a biotechnology company. In collaboration with Stoke, Dr. Isom and her team tested the ASO called STK-001 in a Dravet syndrome mouse model.

"The brain normally uses sections of genes called poison exons to dial up or down the expression of a particular gene, as an internal regulatory mechanism," explains Isom. "We are taking advantage of a poison exon in SCN1A to increase its expression." Unlike using CRISPR, viruses, or other forms of gene editing, ASOs are reversible. "The problem with gene therapy is you are changing something forever, which is risky especially with the brain. If you make a mistake, there's no going back."

Injecting the ASO into the brains of mice that carry only one healthy copy of the SCN1A gene two days after they were born led to 97 percent survival out to 90 days, while just 23 percent of the untreated mice survived during the same time range. "Our thought is that early intervention with an ASO in mice may be able to change brain excitability," says Isom, "And if that's also true for kids with Dravet...that would be incredible." The results are published in the journal Science Translational Medicine.

Based on the encouraging findings of the mouse study, Stoke has recently launched a clinical study to begin evaluating STK-001 in children and adolescents with Dravet syndrome.

Isom notes that the mouse study could have even wider implications for treating the genetic cause of generalized epilepsy, especially for the third of patients whose epilepsy is not controlled with traditional drugs. "We just need to start over and think about epilepsy in a new light--to get at the genetic source, rather than being reactive and trying to treat something that has already happened."

BOSTON -Xu Yu, MD, Ragon group leader, recently published a study entitled "Distinct viral reservoirs in individuals with spontaneous control of HIV-1," in Nature. Yu's lab, in collaboration with Ragon group leaders Mathias Lichterfeld, MD, PhD, and Mary Carrington, PhD, and Ragon director, Bruce Walker, MD, sequenced billions of cells from 64 elite controllers, people living with HIV who suppress the virus naturally without the need for medication, and 41 individuals on antiretroviral drugs (ART). Unlike ART-treated individuals, elite controllers' viral reservoirs appear to be incapable of being reactivated. This likely helps the elite controllers maintain spontaneous, drug-free control of HIV and may represent a distinguishing feature for a functional cure of HIV infection.

HIV affects more than 35 million people worldwide and can be effectively controlled, but not cured, with a daily regimen of ART. Upon infection, retroviruses like HIV place copies of their viral genetic material into cells' genomes, creating viral reservoirs, sanctuaries where HIV persists despite ART, throughout the body. When a complete copy of the virus, or intact viral genome, is incorporated into a cell's genome, it can be used to create new copies of HIV. For people living with HIV, this means that if they stop taking ART, the intact viral genomes previously integrated into the cells' genomes start making new copies of the virus, leading to rapid viral rebound and disease progression. The HIV viral reservoir has remained a major obstacle to an HIV cure.

Elite controllers' immune systems use a T-cell mediated immune response to control the virus without medication, to the point that the virus is completely undetectable by standard assays. Understanding the interplay between their immune system and HIV may hold the key to helping the immune systems of people living with HIV to suppress the virus without daily treatment, achieving what is known as a functional cure.

Yu's group studied the viral reservoir in elite controllers, using next-generation sequencing techniques to precisely map the locations of intact HIV genomes in the human genome. They found that in elite controllers, HIV was often found in locations of the genome that researchers call gene deserts. In these inactive parts of the human genome, human DNA is never turned on, and HIV cannot be effectively expressed but remains in a "blocked and locked" state. This means that HIV is locked in the cell's genome, and the viral genome is blocked from being used to create more viruses and is therefore incapable of causing disease.

"This positioning of viral genomes in elite controllers," Yu, says, "is highly atypical, as in the vast majority of people living with HIV-1, HIV is located in the active human genes where viruses can be readily produced."

When the authors collected cells from elite controllers and infected them with HIV in the lab, they found the virus integrated into active sites in the cell genomes, not in the inactive gene deserts. This suggests that the elite controllers' unique viral reservoirs may be a result of their HIV-suppressing T cell response eliminating intact viral genomes from active sites.

If researchers are able to identify which viral reservoirs can make new copies of the virus after treatment stops, it may help them to target a treatment against the active, or rebound-competent, reservoirs. This study suggests that if researchers can activate the kind of T cell immunity that is present in elite controllers, they may be able to eliminate rebound-competent viral reservoirs in people living with HIV, achieving a functional cure. The remaining viral DNA, located in non-active parts of the human genome, could be allowed to exist without causing disease.

Yu's group had one more finding: one of their elite controller participants had no intact HIV found in over 1.5 billion cells analyzed. This raises the possibility that a "sterilizing cure" of HIV, in which the participant's immune system has removed all intact HIV genomes from the body, may be achieved naturally in extremely rare instances.

A new study says that many of the ice shelves ringing Antarctica could be vulnerable to quick destruction if rising temperatures drive melt water into the numerous fractures that currently penetrate their surfaces. The shelves help slow interior glaciers' slide toward the ocean, so if they were to fail, sea levels around the world could surge rapidly as a result. The study appears this week in the leading journal Nature.

Ice shelves are giant tongues of ice floating on the ocean around the edges of the continent. The vast land-bound glaciers behind them are constantly pushing seaward. But because many shelves are largely confined within expansive bays and gulfs, they are compressed from the sides and slow the glaciers' march--somewhat like a person in a narrow hallway bracing their arms against the walls to slow someone trying to push past them. But ice shelves experience a competing stress: they stretch out as they approach the ocean. Satellite observations show that, as a result, they rip apart; most are raked with numerous long fractures perpendicular to the direction of stretching. Fractures that form at the surface can be tens of meters deep; others, forming from the bottom, can penetrate the ice hundreds of meters upward. Some fractures are hundreds of meters wide.

Currently, most of the shelves are frozen year round, and stable. But scientists project that widespread warming could occur later in the century. And, existing research has shown that even subtle temperature swings can spur widespread melting. This could send melt water surging into the surface fractures. Such surges would potentially cause hydrofracturing-a process in which liquid water, heavier than ice, would violently force the fractures to zip open, and cause the shelf to rapidly disintegrate The new study estimates that 50 to 70 percent of the areas of the ice shelves buttressing the glaciers are vulnerable to such processes.

"It's not just about melting, but where it's melting," said lead author Ching-Yao Lai, a postdoctoral researcher at Columbia University's Lamont-Doherty Earth Observatory.

"The ice shelves-that's the weak spot, where the atmosphere, the ice and ocean interact," said study coauthor Jonathan Kingslake, a glaciologist at Lamont-Doherty. "If they fill up with melt water, things can happen very quickly after that, and there could be major consequences for sea levels."

Hydrofracturing has already occurred in a few places. Parts of the Larsen Ice Shelf, which had been stable for at least 10,000 years, disintegrated within just days in 1995 and 2002. This was followed by the partial breakup of the Wilkins Ice Shelf in 2008 and 2009. The main agreed-upon causes: hydrofracturing. The Larsen and Wilkins comprise some of the northernmost ice on the continent, and so have been the first to suffer under rising temperatures and seasonal melting.

The new study follows a 2017 paper led by Kingslake showing that seasonal ponds and streams on the ice surface are far more common across Antarctica than previously believed; some reach within 375 miles of the South Pole. But most cataloged features are in places not subject to hydrofracturing. The new study shows that, so far, only about 0.6 percent of East Antarctic ice shelves that provide buttressing experience melt-water ponding, making them vulnerable. A much larger percentage would potentially be endangered, if warming takes hold.

In collaboration with Cameron Chen, a researcher from Google, Lai trained a machine-learning model to identify ice-shelf fracture locations across Antarctica, to produce the first continent-wide map of such features. Although most fractures now contain no liquid water, the scientists considered future cases in which melt water might fully fill the surface fractures. This allowed them to predict which parts of the shelves would be vulnerable to hydrofracturing, when factoring in the competing forces of compression from the sides, and stretching of the ice from back to front.

They calculated that inflow of liquid into the existing fractures could potentially exert enough force to cause widespread hydrofracturing across 50 to 70 percent of the ice-shelf areas that provide buttressing. The main exceptions were smaller, solider areas of ice closest to land, which experience less stress from stretching. The end portions of the shelves, mostly surrounded by open ocean, are also vulnerable, but floating freely as they do, those do not help hold back the glaciers.

While the study flashes a warning, the researchers say they cannot predict the ice shelves' behavior with any exactitude. "How fast melt water would form and fill in those cracks is the first question," said Kingslake. He said the worst-case scenario would be that "lots of places will be covered by lots and lots of water by the end of the century." But projections vary widely, depending on which models scientists use, and how vigorously humanity cuts greenhouse gases, or not. The second question is whether particular locations will undergo hydrofracturing, he said. The third question: whether the process would run away, causing the shelf to undergo explosive Larsen-type disintegration.

Theodore Scambos, a leading Antarctic glaciologist and the National Snow and Ice Data Center, said the paper "does a great job of pointing to areas where one can say, 'If it floods with melt here, it's likely to break up the shelf." He added that it "has huge implications for sea level" if summer temperatures along the coasts rise.

"Eventually, all the ice shelves could be covered by melt water," said Lai. "But we don't have a time frame, and there are a lot of big questions left."

BOSTON - Inhaled nitric oxide (NO) can be a valuable adjunct respiratory therapy for pregnant women with severe and critical COVID-19, a team of researchers from Massachusetts General Hospital (MGH) has found. The delivery of the therapeutic gas to six COVID-19 pregnant patients admitted to MGH, as described in a paper in Obstetrics & Gynecology, resulted in a rapid and sustained improvement in cardiopulmonary function and decreased inflammation. The resolution of viral infection within 22 days was observed in five of the six patients, findings that could have important implications for treating viruses like Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

"We noted rapid relief from breathlessness in these patients, with lower respiratory rate and better oxygenation after mask administration of high concentration nitric oxide, with no adverse side effects," says Lorenzo Berra, MD, investigator in the Department of Anaesthesia, Critical Care and Pain Medicine at MGH, and the corresponding author of the study. "In addition, inflammatory markers showed a rapid decrease after breathing nitric oxide and five of the six patients in our study showed viral clearance from nasopharyngeal swabs by 22 days after COVID-19 diagnosis. All patients were discharged in stable condition from the hospital. We found these results to be very encouraging."

Inhaled nitric oxide acts as a selective pulmonary vasodilator, increasing oxygenation by dilating or opening constricted blood vessels, especially in more well-ventilated areas of the lung, thereby improving intrapulmonary shunt fraction. Nitric oxide was approved by the U.S. Food and Drug Administration (FDA) in 1999 for the treatment of persistent pulmonary hypertension in newborns. Since then, NO has also been used off-label for many pediatric and adult clinical applications, including pulmonary hypertension in pregnancy, post-cardiac surgery, lung transplantation and acute respiratory distress syndrome (ARDS). The MGH study is the first to investigate the role of inhaled NO in pregnant people with COVID-19.

A recent report from the Centers for Disease Control and Prevention (CDC) suggests that pregnant women with COVID-19 are more likely to be hospitalized, are at increased risk of being admitted to the intensive care unit, and more often require mechanical ventilation compared to nonpregnant women. The lack of effective treatments for patients with severe or critical COVID-19 respiratory symptoms prompted a group of physicians from MGH to form an interdisciplinary team to offer pregnant women a novel treatment with inhaled NO to prevent progressive respiratory failure. Between April and June 2020, six hospitalized pregnant COVID-19 patients were given NO therapy. Each treatment was started within 48 hours of admission at a high but still safe dosage of 160 to 200 parts per million (ppm) of inhaled NO for 30 to 60 minutes twice-a-day.

"Even at that dosage, nitric oxide is easy to use and appears well tolerated," says Bijan Safaee Fakhr, MD, an investigator in the Department of Anaesthesia, Critical Care and Pain Medicine at MGH and lead author of the article. "We found that nitric oxide inhalation therapy provided rapid relief of shortness of breath in these patients and that their respiratory rates decreased." Moreover, he notes that three of the six women delivered four babies, including a set of twins, while in the hospital, and that each infant tested negative for COVID-19 and remained in good condition 28 days after maternal admission. These findings suggested to Safaee Fakhr that inhaled NO could result in improved placental oxygenation by improving maternal oxygenation.

The MGH physicians were further intrigued by the potential antiviral activity of inhaled NO in patients with COVID-19. Berra, who is also an associate professor of Anesthesia at Harvard Medical School cited a group of clinicians in China who, during the 2003-2004 SARS outbreak, administered inhaled NO to infected patients and reported that their chest x-ray findings cleared rapidly (Chen et al. Clin Infect Dis. 2004;39(10):1531-5). "Because of the genetic similarities between Coronavirus SARS-CoV-1 (SARS) and CoV-2 (COVID-19), we decided to use high-dose nitric oxide to prevent viral replication," Berra explains. What the physicians learned was that five of the six patients in their cohort who received inhaled NO but no other antiviral medication while in the hospital were clear of the virus, as shown by two negative nasopharyngeal swabs obtained after 9 to 22 days from treatment initiation.

"Additional randomized clinical trials are needed to confirm the antiviral effects and definitively determine the efficacy of inhaled nitric oxide on SARS-CoV-2," says Berra. "Irrespective of that, the cardiopulmonary, anti-inflammatory, and possible mild bronchodilatory effects of NO, coupled with its safety profile, offer clear evidence to support using high dose NO therapy for respiratory failure in pregnant women to combat a still unknown disease like COVID-19."

By making use of enzymes found in the digestive tract, MIT engineers have devised a way to apply a temporary synthetic coating to the lining of the small intestine. This coating could be adapted to deliver drugs, aid in digestion, or prevent nutrients such as glucose from being absorbed.

In a study conducted in pigs, the researchers demonstrated that they could use this approach to simplify the delivery of medications that normally have to be taken multiple times per day. They also modified the coatings to deliver the enzyme lactase, which helps people digest the milk sugar lactose, and to block glucose absorption, which could offer a new strategy to treat diabetes or obesity.

"These three applications are fairly distinct, but they offer a sense of the breadth of things that can be done with this approach," says Giovanni Traverso, an MIT assistant professor of mechanical engineering, a gastroenterologist at Brigham and Women's Hospital, and the senior author of the study.

The lining consists of a polymer made from dopamine molecules, which can be consumed as a liquid. Once the solution reaches the small intestine, the molecules are assembled into a polymer, in a reaction catalyzed by an enzyme found in the small intestine.

Junwei Li, a postdoc at MIT's Koch Institute for Integrative Cancer Research, is the lead author of the study, which appears in Science Translational Medicine.

Sticky polymers

The MIT team began working on this project with the goal of trying to develop liquid drug formulations that could offer an easier-to-swallow alternative to capsules, especially for children. Their idea was to create a polymer coating for the intestinal lining, which would form after being swallowed as a solution of monomers (the building blocks of polymers).

"Children often aren't able to take solid dosage forms like capsules and tablets," Traverso says. "We started to think about whether we could develop liquid formulations that could form a synthetic epithelial lining that could then be used for drug delivery, making it easier for the patient to receive the medication."

They took their inspiration from nature and began to experiment with a polymer called polydopamine (PDA), which is a component of the sticky substance that mussels secrete to help them cling to rocks. PDA is made from monomers of dopamine -- the same chemical that acts as a neurotransmitter in the brain.

The researchers discovered that an enzyme called catalase could help assemble molecules of dopamine into the PDA polymer. Catalase is found throughout the digestive tract, with especially high levels in the upper region of the small intestine.

In a study conducted in pigs, the researchers showed that if they deliver dopamine in a liquid solution, along with a tiny amount of hydrogen peroxide (at levels recognized to be safe), catalase in the small intestine breaks the hydrogen peroxide down into water and oxygen. That oxygen helps the dopamine molecules to join together into the PDA polymer. Within a few minutes, a thin film of PDA forms, coating the lining of the small intestine.

"These polymers have muco-adhesion properties, which means that after polymerization, the polymer can attach to the intestinal wall very strongly," Li says. "In this way, we can generate synthetic, epithelial-like coatings on the original intestinal surface."

Once the researchers developed the coating, they began experimenting with ways to modify it for a variety of applications. They showed that they could attach an enzyme called beta-galactosidase (lactase) to the film, and that this film could then help with lactose digestion. In pigs, this coating improved the efficiency of lactose digestion around 20-fold.

For another application, the researchers incorporated a drug called praziquantel, which is used to treat schistosomiasis, a tropical disease caused by parasitic worms. Usually this drug has to be given three times a day, but using this formulation, it could be given just once a day and gradually released throughout the day. This approach could also be useful for antibiotics that have to be given more than once a day, the researchers say.

Lastly, the researchers showed that they could embed the polymer with tiny crosslinkers that make the coating impenetrable to glucose (and potentially other molecules). This could help in the management of diabetes, obesity, or other metabolic disorders, the researchers say.

Temporary coating

In this study, the researchers showed that the coating lasts for about 24 hours, after which it is shed along with the cells that make up the intestinal lining, which is continually replaced. For their studies in pigs, the researchers delivered the solution by endoscopy, but they envision developing a drinkable formulation for human use. The researchers are also developing other alternative formulations, including capsules and pills.

The researchers performed some preliminary safety studies in rats and found that the dopamine solution had no harmful effects. Their studies also suggested that most or all of the dopamine molecules become part of the synthetic coating and do not make it into the tissue or the bloodstream, but the team plans to do additional safety studies to explore any possible effects the dopamine may have.

Moreover, the researchers investigated the nutrient absorption capacity of the intestine after 24 hours and showed no difference between animals that had received the gastrointestinal synthetic epithelial lining (GSEL) and those that hadn't received the GSEL.

Additionally, the team found that the coating was able to stick well to human GI tissue.

Early in the COVID-19 pandemic, Mount Sinai researchers were among the first to show that anticoagulation therapy was associated with improved survival among hospitalized COVID-19 patients. But many questions remained--about the size of the potential benefit, and about what dosage of this therapy might be more effective. Now, the research team has suggested some possible answers, in a paper published in the August 26 online issue of the Journal of the American College of Cardiology.

In this observational study, the researchers found all regimens of anticoagulants--drugs that prevent blood clotting--were far superior to no anticoagulants in COVID-19 patients. More specifically, patients on both a "therapeutic" or full dose, and those on a "prophylactic" or lower dose, showed about a 50 percent higher chance of survival, and roughly a 30 percent lower chance of intubation, than those not on anticoagulants. The researchers looked at six different anticoagulant regimens, including both oral and intravenous dosing, within both therapeutic and prophylactic groups. They observed that therapeutic and prophylactic subcutaneous low-molecular weight heparin, and therapeutic oral apixaban may lead to better results.

"This work from the Mount Sinai COVID Informatics Center provides additional insight on the role of anticoagulation in the management of patients admitted to the hospital with COVID-19. Although this is an observational study, it helped in the design of a large-scale international clinical trial that we are coordinating. The randomized trial focuses on those three antithrombotic regimens-- therapeutic and prophylactic subcutaneous low-molecular weight heparin, and therapeutic oral apixaban," says senior corresponding author Valentin Fuster, MD, PhD, Director of Mount Sinai Heart and Physician-in-Chief of The Mount Sinai Hospital.

This study is an extension of Mount Sinai research that showed that treatment with anticoagulants was associated with improved outcomes both in and out of the intensive care unit among hospitalized COVID-19 patients. The work was prompted by the discovery that many patients hospitalized with COVID-19 developed high levels of life-threatening blood clots.

The team of investigators evaluated electronic medical records of 4,389 confirmed COVID-19-positive patients admitted to five hospitals in the Mount Sinai Health System in New York City (The Mount Sinai Hospital, Mount Sinai West, Mount Sinai Morningside, Mount Sinai Queens, and Mount Sinai Brooklyn) between March 1 and April 30, 2020. They specifically looked at survival and death rates for patients placed on therapeutic and prophylactic doses of blood thinners (oral antithrombotics, subcutaneous heparin, and intravenous heparin) versus those not placed on blood thinners. The researchers used a hazard score to estimate risk of death, which took relevant risk factors into account before evaluating the effectiveness of anticoagulation, including age, ethnicity, pre-existing conditions, and whether the patient was already on blood thinners. The researchers also took into account and corrected for disease severity, including low oxygen saturation levels and intubation.

Of the patients analyzed, 900 (20.5 percent) received a full-treatment dose of anticoagulants. Another 1,959 patients (44.6 percent) received a lower, prophylactic dose of anticoagulants, and 1,530 (34.5 percent) were not given blood thinners. There was a strong association between blood thinners and reduced likelihood of in-hospital deaths: both therapeutic and prophylactic doses of anticoagulants reduced mortality by roughly 50 percent compared to patients on no blood thinners.

Overall, 467 (10.6 percent) of the patients required intubation and mechanical ventilation during their hospitalization. Those on therapeutic blood thinners had 31 percent fewer intubations than those not on blood thinners, while those on prophylactic blood thinners had 28 percent fewer.

Bleeding rates--a known complication of blood thinners--were surprisingly low overall among all patients (three percent or less), but slightly higher in the therapeutic group compared to the prophylactic and no-blood-thinner groups, the researchers said. Their findings suggest that clinicians should evaluate patients on an individual basis given the benefit-risk tradeoff.

Separately, the researchers looked at autopsy results of 26 COVID-19 patients and found that 11 of them (42 percent) had blood clots--pulmonary, brain, and/or heart--that were never suspected in the clinical setting. These findings suggest that treating patients with anticoagulants may be associated with improved survival.

"This report is much more in-depth than our previous brief report and includes many more patients, longer follow-up, and rigorous methodology. Clearly, anticoagulation is associated with improved outcomes and bleeding rates appear to be low," says corresponding author Anu Lala, MD, Assistant Professor of Medicine (Cardiology) and Director of Heart Failure Research at the Icahn School of Medicine at Mount Sinai. "As a clinician who has treated COVID-19 patients on the front lines, I recognize the importance of having answers as to what the best treatment for these patients entails, and these results will inform the design of clinical trials to ultimately give concrete information."

"These observational analyses were done with the highest level of statistical rigor and provide exciting insights into the association of anticoagulation with critical in-hospital outcomes of mortality and intubation," says first author Girish Nadkarni, MD, Co-Founder and Co-Director of the Mount Sinai COVID Informatics Center and Clinical Director of the Hasso Plattner Institute for Digital Health at Mount Sinai. "We are excited that results from this observational study in one of the largest and most diverse hospitalized populations have led to an ongoing trial of type, duration, and doses of anticoagulation. Ultimately we hope this work will lead to improved outcomes and treatment for COVID-19 patients."

"This work highlights the need to better understand the disease from a diagnostic and therapeutic point of view and the importance of conducting properly designed diagnostic and interventional studies," explains co-author Zahi Fayad, PhD, Co-Founder of the Mount Sinai COVID Informatics Center and Director of Mount Sinai's BioMedical Engineering and Imaging Institute.

Philadelphia, August 26, 2020 - A team of researchers at Children's Hospital of Philadelphia (CHOP) affiliated with the CHOP Epilepsy Neurogenetics Initiative (ENGIN) have combined clinical information with large-scale genomic data to successfully link characteristic presentations of childhood epilepsies with specific genetic variants. The findings were published today in the American Journal of Human Genetics.

Developmental and Epileptic Encephalopathies (DEE), a group of severe brain disorders that can cause difficult-to-treat seizures, cognitive and neurological impairment, and, in some cases, early death, are known to have more than 100 underlying genetic causes. However, matching characteristic clinical features and outcomes with specific genetic mutations can be especially daunting given the large number of genetic causes, each of which is very rare.

When genetic information is collected, a person's phenotype - or clinical features - are typically also documented. However, while genetic information is collected in a standardized manner, the same is not true when describing clinical symptoms, which makes it difficult when trying to pinpoint whether certain genetic mutations are responsible for specific clinical features.

Building upon their previous work, researchers from CHOP utilized the Human Phenotype Ontology (HPO), which provides a standardized format to characterize a patient's phenotypic features and allows clinical data to be used at a similar level as genetic data.

"For this study, we used phenotypic and genetic information that had been collected in several important cohorts for more than a decade," said Ingo Helbig, MD, attending physician at ENGIN, director of the genomic and data science core of ENGIN and lead investigator of the study. "In this study alone, we found associations of 11 genetic causes with specific phenotypes. Without methods to systematically analyze clinical data, we could not have possibly done this previously, even with this robust cohort of patients."

In total, the study team analyzed 31,742 HPO terms in 846 patients with existing whole exome sequencing data. Some examples of causative genes in DEE identified in this study were SCN1A, which was associated with complex febrile seizures and focal clonic seizures; STXBP1, which was associated with absent speech; and SLC6A1, which was associated with EEG with generalized slow activity. In total, 41 genes with variants presented in at least two individuals, and 11 of those genes showed significant similarity between phenotypes of the patients with changes in these genes. Using a statistical analysis, the researchers showed that this was more than would be possible via chance.

"Traditionally, many of the genetic epilepsies that we now develop treatments for were described because of a specific set of clinical features that stood out. However, this type of traditional description of new diseases requires patients to be seen by the same provider or within the same center. What we have done with this study is re-engineered the cognitive process that goes on when clinicians discover a new syndrome," Helbig said. "We have developed a computational mechanism to replicate this type of discovery from large, de-identified clinical data. As the amount of deep phenotypic data available to us increases, we now have the ability to identify novel genetic causes of particularly severe forms of epilepsy that are targets for new treatments."

Effective solutions to the climate challenge threatening the world's coral reefs require complex decisions about risk and uncertainty, timing, quality versus quantity as well as which species to support for the most robust and productive future, according to a science paper released today.

Interventions to help coral reefs under global change - a complex decision challenge, by a group of key scientists from Australia's Reef Restoration and Adaptation Program (RRAP), was today published in PLOS ONE.

The paper warns that while best-practice conventional management is essential, it is unlikely to be enough to sustain coral reefs under continued climate change. Nor is reducing emissions of greenhouse gases, on its own, sufficient any longer.

Lead author - marine biologist and decision scientist Dr Ken Anthony, of the Australian Institute of Marine Science (AIMS) - said that even with strong action to reduce carbon emissions, global temperatures could stay elevated for decades.

"Coordinated, novel interventions will most likely be needed - combined with best-practice conventional reef management and reduced carbon emissions - to help the Reef become resilient in the face of climate change," he said.

"Developing new technologies for environmental management and conservation carries some risks but delaying action represents a lost opportunity to sustain the Reef in the best condition possible."

Such interventions include local and regional cooling and shading technologies such as brightening clouds to reflect sunlight and shade the reef, assisting the natural evolution of corals to increase their resilience to the changing environment, and measures to support and enhance the natural recovery of damaged reefs.

The paper draws parallels between the risk assessment of coral reef interventions and driverless cars and new drugs. It outlines the prioritisation challenges and the trade-offs that need to be weighed.

"For example, should we aim to sustain minimal coral cover over a very large area of the reef or moderate coral cover over a smaller area?" he said.

"While the net result of coral area sustained may be the same, it could produce very different ecological outcomes and values for industries like tourism.

"Spreading efforts thinly could reduce the Reef's capacity to sustain critical ecological functions, while concentrating efforts on a selection of just a few reefs could sustain most of the Reef's tourism industry, which is spatially concentrated.

"But under severe climate change, preserving more coral cover in smaller areas could reduce the Great Barrier Reef to a fragmented (and therefore vulnerable) network of coral oases in an otherwise desolate seascape."

Dr Anthony said prioritising the coral species to be supported by adaptation and restoration measures added to the decision challenge for reef restoration and adaptation.

"Without significant climate mitigation, sensitive coral species will give way to naturally hardier ones, or to species that can adapt faster," he said.

"Picking who should be winners, and ultimately who will be losers under continued but uncertain climate change is perhaps the biggest challenge facing R&D programs tasked with developing reef rescue interventions."

Co-author and AIMS CEO Dr Paul Hardisty said how interventions were chosen and progressed for research and development would determine what options were available for reef managers and when.

"Ultimately, we need to consider what society wants, what can be achieved and what opportunities we have for action in a rapidly closing window," he said.

"It will require exceptional coordination of science, management and policy, and open engagement with the Traditional Owners and the general public. It will also require compromise, because reefs will change under climate change despite our best interventions."

RRAP is a partnership of organisations working together to create an innovative toolkit of safe, acceptable, large-scale interventions to helping the Reef resist, adapt to, and recover from the impacts of climate change.

In April, the Australian Government announced that an initial $150M would be invested in the RRAP R&D Program following endorsement of a two-year feasibility study. Of this, $100M is through the $443.3 million Great Barrier Reef Foundation - Reef Trust Partnership with a further $50M in research and scientific contributions from the program partners.

Dr Hardisty said RRAP aimed to research and develop new methods for management quickly and safely.

"We need to be expediently trialling promising interventions now, whatever emissions trajectory the world follows," he said.

"In this paper we offer a conceptual model to help reef managers frame decision problems and objectives, and to guide effective strategy choices in the face of complexity and uncertainty."

Plants have a unique ability to safeguard themselves against pathogens by closing their pores--but until now, no one knew quite how they did it. Scientists have known that a flood of calcium into the cells surrounding the pores triggers them to close, but how the calcium entered the cells was unclear.

A new study by an international team including University of Maryland scientists reveals that a protein called OSCA1.3 forms a channel that leaks calcium into the cells surrounding a plant's pores, and they determined that a known immune system protein triggers the process.

The findings are a major step toward understanding the defense mechanisms plants use to resist infection, which could eventually lead to healthier, more resistant and more productive crops. The research paper was published on August 26, 2020 in the journal Nature.

"This is a major advance, because a substantial part of the world's food generated by agriculture is lost to pathogens, and we now know the molecular mechanism behind one of the first and most relevant signals for plant immune response to pathogens--the calcium burst after infection," said José Feijó, a professor of cell biology and molecular genetics at UMD and co-author of the study. "Finding the mechanism associated with this calcium channel allows further research into its regulation, which will improve our understanding of the way in which the channel activity modulates and, eventually, boosts the immune reaction of plants to pathogens."

Plant pores--called stomata--are encircled by two guard cells, which respond to calcium signals that tell the cells to expand or contract and trigger innate immune signals, initiating the plant's defense response. Because calcium cannot pass directly through the guard cell membranes, scientists knew a calcium channel had to be at work. But they didn't know which protein acted as the calcium channel.

To find this protein, the study's lead author, Cyril Zipfel, a professor of molecular and cellular plant physiology at the University of Zurich and Senior Group Leader at The Sainsbury Laboratory in Norwich, searched for proteins that would be modified by another protein named BIK1, which genetic studies and bioassays identified as a necessary component of the immune calcium response in plants.

When exposed to BIK1, one protein called OSCA1.3 transformed in a very specific way that suggested it could be a calcium channel for plants. OSCA1.3 is a member of a widespread family of proteins known to exist as ion channels in many organisms, including humans, and it seems to be specifically activated upon detection of pathogens.

To determine if OSCA1.3 was, in fact, the calcium channel they were looking for, Zipfel's team reached out to Feijó, who is well known for identifying and characterizing novel ion channels and signaling mechanisms in plants. Erwan Michard, a visiting assistant research scientist in Feijó's lab and co-author of the paper, conducted experiments that revealed BIK1 triggers OSCA1.3 to open up a calcium channel into a cell and also explained the mechanism for how it happens.

BIK1 only activates when a plant gets infected with a pathogen, which suggests that OSCA1.3 opens a calcium channel to close stomata as a defensive, immune system response to pathogens.

"This is a perfect example of how a collaborative effort between labs with different expertise can bring about important conclusions that would be difficult on solo efforts," Feijó, said. "This fundamental knowledge is badly needed to inform ecology and agriculture on how the biome will react to the climatic changes that our planet is going through."

Feijó, will now incorporate this new knowledge of the OSCA1.3 calcium channel into other areas of research in his lab, which is working to understand how the mineral calcium was co-opted through evolution by all living organisms to serve as a signaling device for information about stressors from infection to climate change.

"Despite the physiological and ecological relevance of stomatal closure, the identity of some of the key components mediating this closure were still unknown," Zipfel said. "The identification of OSCA1.3 now fills one of these important gaps. In the context of plant immunity this work is particularly apt in 2020, the UN International Year of Plant Health."

Researchers from Linköping University suggest a process by which the timid junglefowl from the rain forest could have become today's domesticated chicken. When the scientists selectively bred the junglefowl with least fear of humans for 10 generations, the offspring acquired smaller brains and found it easier to become accustomed to frightening but non-hazardous events. The results shed new light over how domestication may have changed animals so much in a relatively short time.

Chickens are the most common birds on Earth. There are currently more than 20 billion individuals on the planet. All of them have come from the Red Junglefowl, originally found in south-east Asia. This species was tamed and domesticated by humans approximately 10,000 years ago. The results of the current study show that when our ancestors selected the tamest individuals for breeding, they may at the same time have unconsciously selected birds with a different brain - one that may have been more suitable for a life among humans. The findings are published in Royal Society Open Science.

Researchers Rebecca Katajamaa and Per Jensen started with a group of wild Red Junglefowl and selected as parents the birds that showed least fear of humans in a standard test. The breeding experiment was conducted for 10 generations. The birds that showed greatest fear of humans were placed into a second group. The researchers believe that they have in this way imitated the factor that must have been the most important during early domestication, namely that it was possible to tame the animals.

A somewhat unexpected result of the breeding was that the brains of the domesticated birds gradually became smaller relative to body size, which mirrors what has happened to modern domesticated chickens during the domestication process. The change was particularly pronounced in the brain stem, a primitive part of the brain that is involved in, among other things, certain stress reactions. The brain stem was relatively smaller in animals that were not overly timid.

The scientists carried out two behavioural experiments, to determine whether the difference in brain size and composition affected the ability of the fowl to learn. One test investigated how rapidly the birds became accustomed to something that could be experienced as frightening, but which was actually non-hazardous, in this case a flashing light. The tame birds became accustomed and stopped reacting to the stimulus significantly more rapidly.

"We believe that the ability to become accustomed rapidly is beneficial for the birds that are to live among humans, where events that are unknown and frightening, but not dangerous, are part of everyday life", says Rebecca Katajamaa, doctoral student in the Department of Physics, Chemistry and Biology at Linköping University.

The researchers also investigated whether the birds differed in the ability to learn to associate two things with each other, such as coupling a certain pattern with food. This process is known as "associative learning". However, they found no differences between the two groups.

It is not possible to say whether the differences in behaviour shown in the study are directly connected with the differences in brain size and composition. The researchers plan to investigate this in more detail.

"Our study not only sheds light on a possible process by which chickens - and possibly other species - become domesticated. It may also give new insight into how the structure of the brain is connected with differences in behaviour between individuals and species", says Per Jensen, professor in the Department of Physics, Chemistry and Biology at Linköping University.

More than half of patients hospitalized with suspected COVID-19 in Michigan during the state's peak months received antibiotics soon after they arrive, just in case they had a bacterial infection in addition to the virus, a new study shows. But testing soon showed that 96.5% of them only had the coronavirus, which antibiotics don't affect.

The 3.5% of patients who arrived at the hospital with both kinds of infection were more likely to die. But the study suggests that faster testing and understanding of infection risk factors could help hospital teams figure out who those patients are - and spare the rest of their COVID-19 patients the risks that come with overuse of antibiotics.

The new paper, published in Clinical Infectious Diseases by a team from the University of Michigan, VA Ann Arbor Healthcare System and St. Joseph Mercy Health Care System, is based on data from more than 1,700 hospitalized patients.

The data came from 38 hospitals taking part in a massive statewide effort called Mi-COVID19 that launched within weeks of the first case of COVID-19 being diagnosed in Michigan on March 10. It leverages the power of multiple quality improvement efforts sponsored by Blue Cross Blue Shield of Michigan.

During March and April, Michigan was one of the nation's early hotspot states, and the authors hope the new data will help patient care teams in current and future hotspots. Inpatient COVID-19 treatment guidelines shared by Michigan Medicine, U-M's academic medical center, have been updated based on these results.

Variation and change

In addition to widespread overuse of antibiotics, the study shows that hospitals varied widely in their use of antibiotics among people newly hospitalized for suspected COVID-19. In some, only a quarter of suspected COVID-19 patients received them within two days of being hospitalized, while in others, nearly all did.

As time went on, and COVID-19 test turnaround time shortened, the use of antibiotics dropped - but was still too high, says Valerie Vaughn, M.D., M.Sc., the study's lead author and a hospitalist physician who helped launch Michigan Medicine's COVID-19 intensive care units.

"For every patient who eventually tested positive for both SARS-Cov2 and a co-occurring bacterial infection that was present on their arrival, 20 other patients received antibiotics but turned out not to need them," says Vaughn. "These data show the crucial importance of early and appropriate testing, with rapid turnaround, to ensure appropriate use of antibiotics and reduce unneeded harm."

In addition to putting patients at risk of opportunistic infections like Clostridium difficile that can worsen their odds of recovery, antibiotics also pose a broader risk of feeding the epidemic of drug-resistant bacteria that already plagues many hospitals and can put patients and staff at risk.

Massive data

The new study wouldn't have been possible without the Mi-COVID19 registry, which includes detailed data from pre-, post- and in-hospital care on COVID-19 patients treated in hospitals of all sizes and kinds across Michigan.

Mi-COVID19 draws on the network of trained data-harvesting nurses and other staff, and physician partners, who before the pandemic focused on studying and improve care for hospitalized patients through a type of organization called a collaborative quality initiative or CQI.

The Mi-COVID19 effort is based in a CQI called the Michigan Hospital Medicine Safety Consortium, working in partnership with 11 other CQIs all sponsored by BCBSM. Additional publications about COVID-19 care are now being prepared that will draw on the data generated by the partnership.

Older people, people who had come to the hospital from a nursing home, and people who were admitted straight to intensive care were more likely to turn out to have a bacterial infection in addition to coronavirus. Half of these patient died, compared with 18% of those without bacterial infections.

Those who received antibiotics were more likely to be older, to have lower body mass index measurements, to have visible signs of infection on their chest X-ray, and to be in more critical condition when they arrive at the hospital.

The importance of rapid and appropriate testing

Vaughn, who has studied and worked to improve antibiotic prescribing for hospitalized pneumonia patients, notes that COVID-19 differs in important ways from regular pneumonia, so standard "antibiotic stewardship" techniques may not work.

For instance, many suspected COVID-19 patients had their blood tested soon after admission to the hospital to look for a substance called procalcitonin, which is often used as an early indicator of bacterial infection while doctors wait for more definitive test results.

Just over half of those who turned out to have a bacterial infection plus COVID-19 had a high procalcitonin reading. But so did 22% of those who didn't have bacterial infections. However, a low procalcitonin reading was almost certain to mean that the person didn't have a bacterial infection.

However, elevated white blood cell counts were a good predictor of who had a bacterial infection.

The faster patients got their COVID-19 viral test results back, the faster their antibiotics were stopped. Half were stopped within a day of a positive coronavirus test. The turnaround time for such tests decreased over time, with 89% getting their results within a day in May compared with 54% in March.

The vast majority of the patients tested for bacterial infections didn't have test that look in the respiratory tract. This may be because these tests require health workers to interact with patients' airways -- which can generate aerosols and risk transmitting coronavirus -- or because they require a sample of coughed-up sputum, which most of the patients didn't have because of the 'dry cough' that typifies COVID-19.

"Since their SARS-Cov2 infection explains their symptoms, we should all be more judicious with prescribing antibiotics unless we see signs of a bacterial infection," says Vaughn. "We need better guidance to help clinicians figure out if the cause of a rapid decline in condition is due to cytokine storm or bacterial infection, and better antibiotic stewardship programs to support physicians in determining if they need to order antibiotics and if so, for how long and with what tests for bacterial infection."

The study actually undercounts the percentage of patients who received antibiotics, Vaughn notes, because it left out those who received azithromycin. For a time that powerful drug was seen as promising for COVID-19 patients, in combination with hydroxychloroquine, though it has since been shown to be ineffective or even potentially harmful.

Patients who were transferred to another hospital as part of their initial COVID-19 stay were also omitted from the analysis.

Like humans, plants protect themselves against pathogens. An international consortium under the lead of UZH professor Cyril Zipfel has now identified a long sought-after factor of this plant immune system: The calcium channel triggers the closure of stomata upon contact with microbes such as bacteria. This innate defense mechanism could help to engineer crop plants that are resistant to pathogens.

Each plant leaf has hundreds of tiny pores that enable the exchange of gases with the environment. By inhaling CO2 and releasing oxygen and water vapor, these stomata are essential for photosynthesis, the survival of plants - and ultimately all life on this planet. The size of the openings is dynamically controlled to allow plants to adapt to changing conditions like sunlight, drought and rain. The opening and closing is facilitated through the swelling and shrinking of two so-called guard cells that form a ring-like border around the pore.

Plants can defend themselves

Plant researchers have long known that leaves also batten down the hatches when they encounter potentially pathogenic microbes. This reaction is part of the innate plant immune system: Receptors at the surface of plant cells recognize typical structures of microbes such as parts of bacterial flagellae. This leads to a series of reactions that ultimately block microbe entry and multiplication. One of these responses is stomatal closing, which is equivalent to closing the gates to the pathogens.

Long search for a missing link

However, the mechanism behind this microbe-induced closure of stomata remained largely unexplained, although it was shown that a rapid influx of calcium ions into the guard cells triggered the reaction. "The identity of the channels that mediate this rapid calcium movement was still unknown and has vexed researchers for a long time," says Cyril Zipfel, professor of molecular and cellular plant physiology at the University of Zurich and senior group leader at the Sainsbury Laboratory in Norwich, UK. After six years of research, he has now published a study that closes this gap and identifies the relevant calcium channel in the model plant Arabidopsis. As well as Zipfel's team, several international research groups contributed to the results.

Microbes trigger channel opening

The decisive clue was that the identified channel protein, OSCA1.3 - with a hitherto unknown function - was modified by an important component of the plant immune system. This modification leads to the opening of the OSCA1.3 channel, the influx of calcium ions into the guard cells and the closing of the stomata. Zipfel's team could show that this reaction was specifically initiated when Arabidopsis plants were brought into contact with parts of bacterial flagellae - one of the microbial triggers of the plant immune system.

Specific to immune response

The researchers confirmed this result by introducing several genetic mutations that abolished the function of the OSCA1.3 calcium channel. In these mutated plants, the microbial trigger did not lead to the closing of the pores. Further experiments showed that the channel is also not activated by drought and salinity, other environmental factors that induce the closure of stomata. "This finding reveals the first plant calcium channel with a role in stomatal closure," says Zipfel. "Interestingly, this channel seems specific to plant immunity." He therefore speculates that other plant calcium channels from the same family may respond specifically to other stress factors like drought. This will be the topic of future research.

"Obviously, this channel is involved in an important immune response in plants," says Zipfel. "These findings therefore have the potential to help with the engineering of pathogen-resistant crops." Under real and significant threat by pathogens the plants could then close the gates that would normally allow dangerous microbes to enter into their tissues.

How can the course of the corona pandemic and its effects be illustrated? In recent months, dashboards - interactive, graphically depicted online summaries - have become the new norm of displaying infection rates, deaths and patterns of spread. This is problematic, as geographer Professor Jonathan Everts at Martin Luther University Halle-Wittenberg (MLU) writes in a commentary for the journal Dialogues in Human Geography. He criticises the way the programmes are handled and explains which aspects of the pandemic they are not taking into account.

Dashboards are computer programmes that compile various data, information and statistics about a topic and graphically present them as concisely as possible. These can be simple figures, diagrams or enriched maps. During the corona pandemic, the "COVID-19 Map", produced by Johns-Hopkins University in the U.S., has been held up as the standard. "A dashboard always suggests that you are getting a summary of all the important data," says Jonathan Everts. The data are updated in almost real time and can be viewed by everyone. This is problematic, explains Everts, because these tools are no longer only being used by health authorities, but instead by many people around the world.

Everts says that dashboards often lack a clear explanation, either precise or in general, as to how these figures are compiled. "These values are actually way too complex to be used like this. This leads to overly simplified explanations for very complex phenomena," he criticises.

One example of this is mortality rates, which can vary dramatically from region to region. "These differences cannot be explained solely by the health and prevention measures taken locally. However, dashboards suggest that they can be depicted geographically," says Everts. In order to understand the causes better, there needs to be a differentiation of regional and demographic features, but this usually is not done in dashboards. For example, they do not provide any information about the social groups and places where the virus is spreading particularly fast at a local level. However, this information is necessary if appropriate measures to contain the virus are to be taken, says Everts.

Focusing on individual indicators, such as declining case numbers, could quickly create the false impression that the crisis will soon be over. Another possible side effect could be, that the potential long-term negative effects of the pandemic and the measures taken to control them might go unnoticed: "There is major concern for countries that now face problems in the future as a result of the pandemic. These include countries in Africa, where vaccination campaigns have been interrupted for long periods due to curfews and social distancing. This will create serious problems in the coming years," says Everts. The fact that people might miss routine appointments with physicians out of fear of contracting the new coronavirus could also lead to problems in the medium term, for example high blood pressure or heart attacks might be diagnosed too late. Thus, says Everts, social inequalities remain hidden, which could be further aggravated - or even introduced - by the pandemic.

The human geographer, who also did research on the H1N1 swine flu pandemic of 2009-2010, advocates for a more differentiated and cautious approach to indicators and dashboards in general. "There are two parts to every pandemic crisis: One is the spread of the pathogen around the world, the other is the way society deals with it," he says. There also needs to be a critical, balanced examination of the old problems as well as the new problems created by the pandemic.

With an increase in the elderly and aging population and also in the number of invasive surgeries, wound healing has become a critical focus area in medicine. The complex bodily processes involved in wound healing make it challenging as well as rewarding to identify newer methods and materials for effective wound healing. Now, in a new study, published in Polymers for Advanced Technologies, led by undergraduate student (yes, you read that right) Ryota Teshima, researchers from Tokyo University of Science, Japan, have developed a groundbreaking novel material with possible applications in wound healing. But exactly why is this new material so exciting?

It is important to create an optimal physiological environment around a wound to promote the growth of new cells. Recent research has revealed that a type of material called "hydrogel" is exceptionally useful for achieving such conditions given its molecular structure. Hydrogels are three-dimensionally cross-linked networks of polymers that can absorb more than 95% of their volume in water. Hydrogels with natural polymers have excellent compatibility with the biological conditions of our skin and tissues (referred to as "biocompatibility"), can absorb fluids from the wound, and continuously provide moisture into the wound, creating a highly suitable environment for the wound to heal.

One such natural polymer that is used in hydrogels for wound dressing is alginate, a carbohydrate derived from seaweed, and therefore, abundantly available. Alginate gels are very easy to prepare, but gelation occurs quickly, making it difficult to control the gelation time. Although methods to achieve this control have previously been reported, ensuring short gelation time while maintaining transparency results in hydrogels with a slightly acidic (4-6) or neutral pH. Slightly acidic conditions were, until recently, believed to be beneficial for wound healing, but newer research has found that a slightly alkaline pH (8-8.5) is better for promoting the growth of "skin healing" cells such as fibroblasts and keratinocytes.

This is the context that shaped the characteristics of the next level alginate hydrogel production method that Mr Teshima and his team developed. He summarizes their breakthrough: "We have succeeded in preparing a novel alkaline alginate hydrogel (pH 8.38-8.57) suitable for wound healing via a method that requires no special equipment and can be carried out at room temperature. This, in addition to the fact that the hydrogel forms in 5 minutes, makes it ideal for potential use in any medical practice anywhere for superior wound healing."

Their method involves mixing calcium carbonate and potassium alginate, and then adding carbonated water to this mixture and letting the "gelation" (gel formation) process take place. In this method, the pH of the gel shifts to alkaline because the carbon dioxide volatilizes after gelation. This also ensures transparency of the gel, which in turn allows the visual assessment of wounds and helps in easily ascertaining the progress of healing. Also, regardless of the amounts of ingredients used, the resultant hydrogels have extremely high water content--up to 99%.

When the team placed their hydrogel in physiological saline solution, it passed the test for another critical requisite for a wound dressing: the potential to absorb exudates from the wound. And while the hydrogel did become structurally weak and could not be lifted with tweezers after a week of immersion, it retained its shape.

Speaking about the motivation behind this exciting study, Mr Teshima says, "I have been experimenting with alginate gels ever since junior high school. There was also increasing interest in regenerative medicine when I was growing up, which compelled me to focus on the creation of useful biocompatible materials that can be used in medical therapy." Well, there's no denying that this novel hydrogel developed by Mr Teshima's team shows immense potential for near-future application to wound healing in medicine.

Hopeful of even more potential applications of their method in medicine beyond wound healing, Mr Teshima says, "In the future, if it is possible to control the sustained release of an effective drug held inside it, this novel hydrogel can be used as a drug carrier as well."

For now, the next step is to assess its viability and effectiveness in living cells and animal models. When that is done, Mr Teshima's Japan, and subsequently, the world, can be made a better place.