Culture

CHICAGO (March 9, 2018): For many years, people who sustained severe burn injuries often died. But great strides in burn care over the last 30 years have dramatically increased their chances of survival, according to new study findings published as an "article in press" on the Journal of the American College of Surgeons website ahead of print publication.

"Mortality has decreased three to fivefold since the 1980s, ostensibly from the substantial advances in burn care that occurred between 1980 and 1989," said lead study author David N. Herndon, MD, FACS, chief of staff and director of research at the Shriners Hospitals for Children, Galveston, and director of burn services at the University of Texas Medical Branch (UTMB). "Yet, until now, there has never been a definitive study showing the cumulative effect of these advances on survival."

Burns are one of the leading causes of unintentional death and injury in the U.S., according to the American Burn Association.* Very large burns--those that cover 50 percent or more of the body's surface area--put people at high risk of infection and death. In addition to burn size, old age, female gender, and damage to lungs due to the inhalation of smoke put people at greater risk of death.

This is the most definitive report of the role advanced burn treatment has played in reducing risk of death, the authors said. Dr. Herndon and colleagues examined the records of 10,384 adult and pediatric burn patients admitted to Shriners Hospitals for Children®, Galveston, or the Blocker Burn Unit in Galveston from 1989 to 2017. Over this time period, protocols directly derived from these advances were used to guide care of these patients.

The researchers applied multivariate regression analysis to create a statistical profile of their burn patients and to identify the main factors associated with mortality. Factors such age, sex, burn size, whether the patient suffered smoke inhalation injury (damage to the airways), and length of stay were collected at admission.

Of the 10,384 burn admissions, a total of 355 victims died. The researchers looked specifically at the main factors that influenced risk of death in different age groups and then created a risk prediction model.

Using mortality data from the medical literature, as well as data from the National Burn Repository, the researchers compared historical predictions of mortality risk with their observed patient data. They found a significant decrease in mortality in their patient population compared with historical predictions from previous studies.

"In this one area of medicine, these new protocols have massively reduced mortality overall," Dr. Herndon said. "Over the last 30 years at our burn center there has been a continuing reduction in the risk of mortality of about 2 percent per year in all age groups, burn sizes, and genders."

The study also identified the most powerful predictors of mortality: the percent of total body surface burned, age, and the presence of inhalation injury. The probability of death rose as age increased, as burn size increased, and with the presence of inhalation injury.

The data suggest that the continuous improvement in mortality over time is a result of changes in the standard of care, including protocols for management of inhalation injury; nutrition to combat infection and aid in healing; and receiving early burn excision and skin grafts immediately following injury.

"The most dramatic decreases in mortality most recently have been in patients over age 40," Dr. Herndon said. "Remarkably, a patient up to the age of 40 who has sustained a 95 percent body burn now survives half the time, whereas in earlier times a 50 percent body burn killed that same person."

Other factors not assessed in the study that have contributed to better outcomes in burn patients include improvements in the transfer of critically ill patients to hospitals and burn centers.

"We hope our findings will inspire other burn units to try to keep people alive with extensive burns because it's clear that it can be done. Burn specialists also need to focus on implementing the protocols that have allowed this improvement in survival to occur," Dr. Herndon said. "For example, a woman over the age of 40, with very large burns, is a patient who can survive today if these protocols are implemented."

Beyond the effort to reduce mortality rates in burn victims, researchers hope to concentrate on better treatment strategies to improve quality of life. "Our priorities for future advancements need to focus on decreasing scar tissue and morbidity, effective rehabilitation, and returning patients to work," Dr. Herndon said.

Ocean conditions off most of the U.S. West Coast are returning roughly to average, after an extreme marine heat wave from about 2014 to 2016 disrupted the California Current Ecosystem and shifted many species beyond their traditional range, according to a new report from NOAA Fisheries' two marine laboratories on the West Coast. Some warm waters remain off the Pacific Northwest, however.

The Southwest Fisheries Science Center and Northwest Fisheries Science Center presented their annual "California Current Ecosystem Status Report" to the Pacific Fishery Management Council at the Council's meeting in Rohnert Park, Calif., on Friday, March 9. The California Current encompasses the entire West Coast marine ecosystem, and the report informs the Council about conditions and trends in the ecosystem that may affect marine species and fishing in the coming year.

"The report gives us an important glimpse at what the science is saying about the species and resources that we manage and rely on in terms of our West Coast economy," said Phil Anderson of Westport, Wash., the Council Chair. "The point is that we want to be as informed as we can be when we make decisions that affect those species, and this report helps us do that."

Unusually warm ocean temperatures, referred to as "the Blob," encompassed much of the West Coast beginning about 2014, combining with an especially strong El Nino pattern in 2015. The warm conditions have now waned, although some after-effects remain.

Feeding conditions have improved for California sea lions and seabirds that experienced mass die-offs caused by shifts in their prey during the Blob.

Plankton species, the foundation of the marine food web, have shifted back slightly toward fat-rich, cool-water species that improve the growth and survival of salmon and other fish.

Recent research surveys have found fewer juvenile salmon, and consequently adult salmon returns will likely remain depressed for a few years until successive generations benefit from improving ocean conditions.

Reports of whale entanglements in fishing gear have remained very high for the fourth straight year, as whales followed prey to inshore areas and ran into fishing gear such as pots and traps.

Severe low-oxygen conditions in the ocean water spanned the Oregon Coast from July to September 2017, causing die-offs of crabs and other species.

Even as the effects of the Blob and El Nino dissipate, the central and southern parts of the West Coast face low snow pack and potential drought in 2018 that could put salmon at continued risk as they migrate back up rivers to spawn.

"Overall we're seeing some positive signs, as the ocean returns to a cooler and generally more productive state," said Toby Garfield, a research scientist and Acting Director of the Southwest Fisheries Science Center. "We're fortunate that we have the data from previous years to help us understand what the trends are, and how that matters to West Coast fishermen and communities."

NOAA Fisheries' scientists compile the California Current Ecosystem Status Report from ocean surveys and other monitoring efforts along the West Coast. The tracking revealed "a climate system still in transition in 2017," as surface ocean conditions return to near normal. Deeper water remained unusually warm, especially in the northern part of the California Current. Warm-water species, such as leaner plankton species often associated with subtropical waters, have lingered in these more-northern zones.

One of the largest and most extensive low-oxygen zones ever recorded off the West Coast prevailed off the Oregon Coast last summer, probably driven by low-oxygen water upwelled from the deep ocean, the report said.

While the cooling conditions off the West Coast began to support more cold-water plankton rich in the fatty acids that salmon need to grow, salmon may need more time to show the benefits, the report said. Juvenile salmon sampled off the Northwest Coast in 2017 were especially small and scarce, suggesting that poor feeding conditions off the Columbia River Estuary may remain.

Juvenile salmon that enter the ocean this year amid the gradually improving conditions will not return from the ocean to spawn in the Columbia and other rivers for another two years or more, so fishermen should not expect adult salmon numbers to improve much until then.

"These changes occur gradually, and the effects appear only with time," said Chris Harvey, a fisheries biologist at the Northwest Fisheries Science Center and coauthor of the report. "The advantage of doing this monitoring and watching these indicators is that we can get a sense of what is likely to happen in the ecosystem and how that is likely to affect communities and economies that are closely tied to these waters."

During some kinds of blood donations, you get most of your blood back. For example, platelet donation involves a procedure in which donor blood is filtered to harvest the platelets for medical use and the rest of the blood components are returned to the donor's body. The byproducts of this procedure - a fraction of immune cells - are typically discarded.

Researchers at Iowa State University, partnering with the LifeServe Blood Center, have used these leftover blood donor cells to gain crucial insights into how natural killer cells circulating in the human body differ from those typically studied in the lab. The results of this research are published in the March 9 issue of the Journal of Biological Chemistry.

Adam Barb, an associate professor of biochemistry at Iowa State, studies the receptor CD16a, which is found on the surface of natural killer cells and binds to the antibody immunoglobulin G (IgG). IgG is the most common antibody produced by the human body to coat the surfaces of pathogens or tumors and signal their destruction by natural killer cells. IgG is used as the basis of most antibody immunotherapies, for example against cancer.

How effectively natural killer cells can destroy their targets depends on how tightly the receptor binds to the antibody. Barb's team had previously found that the extent of this attraction, or affinity, depended on the types and amounts of carbohydrates attached to the antibody. In the new study, they set out to find how carbohydrate modifications of the receptor in humans affected the antibody-receptor binding affinity.

"We know that (receptors) can be expressed by the natural killer cell in thousands to millions of different forms," Barb said. "This is because the molecule is coated with complex carbohydrates, like a sugar coat, that can be highly variable."

Because NK cells are found at a low concentration in human blood, researchers who study these receptors typically insert the gene encoding the receptor into cells that can be grown in culture in the lab, an approach called recombinant expression. But it was not clear whether the conditions in cell culture would result in the same carbohydrate modifications to the receptor that occur in the human body.

"All of the work that had been done at that time...was studied with recombinant material, not from primary sources," Barb said. "People had assumed, with respect to this receptor, that the mammalian (cells) used for the recombinant expression would provide the correct types of carbohydrates."

In order to harvest the receptors from the source, Barb's team turned to a nearby blood bank that performed platelet apheresis, because they knew that a fraction of white blood cells were discarded as part of the filtering procedure.

"When the donor is disconnected from the machine, they don't get those (lymphocytes) back, and that filter is usually just thrown away," Barb said. "So basically (they're) concentrating lymphocytes, including natural killer cells, which is exactly what we want, in these filters."

Barb's team obtained these filters from the blood bank and isolated the natural killer cells. They then examined the carbohydrate modifications of receptors from donors' natural killer cells and how these modifications affected binding to antibodies. They found that the carbohydrate modifications in the patients' receptors were much less elaborate than those from recombinant receptors, resulting in higher affinity.

"There was much less (carbohydrate) processing that the NK cells did in comparison to any of the forms that were expressed in these recombinant systems," Barb said. "And as a result of that, the affinity for antibody appears to be higher in natural killer cells than it would be in a receptor that was expressed from recombinant systems. Smaller carbohydrates appear to make for tighter binding interactions."
The study was carried out on natural killer cell samples from donors that were of similar age, sex and blood type, raising the question of how the receptor's carbohydrate modifications may vary in natural populations.

"There appeared to be some degree of variability between donors," Barb said "(But) how does that change throughout the lifetime, how does that change in response to infection? All of those questions are absolutely things that we would very much like to investigate very specifically."

The results suggest that finding ways to influence the carbohydrate modifications of these receptors could be a way to fine-tune antibody-receptor interactions in the context of antibody therapies.

The work was funded by the National Institutes of Health.

A research team ECOSOS (Evolving Cooperation and Social Simulation) led by Hitoshi Yamamoto from Rissho University develops a game theoretical method to analyze what role the diversity of social norms plays in the process of evolving cooperation. The team revealed that a social norm that regards those who help the bad as bad becomes extinct if the members of the society learn their norms based on "dividualism". The study was carried out by collaborating with colleagues Satoshi Uchida (RINRI Institute), Isamu Okada (Soka University), and Tatsuya Sasaki (University of Vienna) and is published in Frontiers in Physics.

People often help others at their own expense without expecting any direct return from the beneficiaries. In order for stable cooperation among people to evolve, the help must be channeled away from exploiters such as defectors who never help others, and directed preferentially towards helpers. This is made possible by a mechanism by which a positive evaluation of the helpful action is shared with others, and the helping person receives a help from a third party at some future time. This mechanism is generally referred to as indirect reciprocity.

Indirect reciprocity relies on social norms that distinguish the good from the bad. Many game theoretical researches have searched for such norms that cooperation is not directed toward the bad, under the assumption that at most a few norms are shared among people. One conclusion of those researches is that assessing those who help the bad as bad stabilizes cooperation. In reality, however, different people often follow different norms, which lead to different opinions of the same person. Little is theoretically known about the evolution of cooperation in "norm ecosystems" in which individuals with different norms interact through helping games.

To address this issue, the team developed an analytical tool which can deal with norm ecosystems. The norm ecosystem studied in the research is so complex that one needs to solve a system of more than sixty thousands equations. But the team at the same time established a method that reduces the system to 512 equations, which can computationally be analyzed. The analysis tells that the norm that assess those who help the bad as bad is stably sustained if people learn their norms based on "individualism" that gives a view that any person cannot be divided into parts and that a person must be treated as a whole. But the same norm becomes extinct once the society adopts "dividualism" that provides a view that a person is constructed from independent parts.

Yamamoto says, "This is a surprising finding since all the theoretical researches so far are based on individualism. Our approach gives a first opportunity to review that premise."

Alport Syndrome (AS) is a hereditary kidney disease caused by a genetic mutation leading to type IV collagen (Col4) abnormalities. Unfortunately, treatment through the correction of Col4 functionality has not yet been developed. Now, researchers from Kumamoto University in Japan have established a highly sensitive technology to assess Col4 functionality thereby paving the way to develop therapeutic drugs. This detection system reduces labor and time costs compared to conventional methods, and monitors the functionality of Col4 with higher sensitivity than ever before. The system also makes it possible to analyze several drug candidate compounds simultaneously.

ACE inhibitors and other medications for treating hypertension have been found to slow the progression of AS. However, this treatment only alleviates symptoms and cannot prevent the transition into end stage renal failure. It is therefore considered that fundamental treatment should focus on the cause of disease onset, an approach that is completely different from prior methods. The therapeutic strategy, in this case, would focus on normalizing the function of the causative protein with a candidate drug compound. If successful, this technique would greatly contribute to the treatment of other hereditary diseases.

[Research]

To normalize the function of the causative protein with a candidate drug compound, it is necessary to efficiently screen and identify compounds that restore the function compromised by the genetic mutation. However, an analysis system to assess the functionality of causative proteins has not yet been developed. Such a system could be used to screen for therapeutic drug candidates. Thus, Kumamoto University researchers aimed to establish a new evaluation system (a compound screening system) just for that purpose.

In Col4, three polypeptide chains (rod-like proteins), alpha-3, alpha-4, and alpha-5, form a complex called a protein trimer. This trimer is a constituent factor of the basement membrane in the part of the kidney called the glomerulus. The glomerular basement membrane is a physical barrier against leakage of blood components during blood filtration, an important kidney function for producing urine. A mutation in any one of the three polypeptide chains can disrupt trimer formation and result in the development of AS due to a failure to properly form the basement membrane. Therefore, it is necessary to search for compounds that can correct or assist trimer formation by mutant collagen.

The researchers used split NanoLuciferase® (split NanoLuc®, NanoBiT®) technology for protein-protein interaction analysis as a method of evaluating trimer formation. Fragments of two large and small luciferase molecules were fused with alpha-3 and alpha-5 chains and expressed in cells with alpha-4 chains. Measurable luminescence was detected only when alpha-3, alpha-4, and alpha-5 chains could form trimers.

The researchers clarified that the NanoLuc-Col4 system reflects previously reported characteristics of Col4, namely that trimers are formed with a fixed combination of alpha-3, alpha-4, and alpha-5 chains, and that alpha-5 chains cannot form trimers if they are missing a functional part. The NanoLuc-Col4 system also revealed that alpha-5 chains with the gene mutations reported in AS failed to function. Importantly, as proof of principle that correcting trimer formation for mutant collagen is feasible, the authors were able to use the system to identify compounds that were able to induce trimer formation of alpha-3, alpha-4 and mutant alpha-5 collagen.

"This research should provide a pathway to develop drugs for hereditary diseases, such as Alport Syndrome, that are currently incurable," said Professor Hirofumi Kai of Kumamoto University's Department of Molecular Medicine.

A new study by scientists from WCS (Wildlife Conservation Society) and other groups predicts that the effects of climate change will severely impact the Albertine Rift, one of Africa's most biodiverse regions and a place not normally associated with global warming.

Of the species existing within this region, the authors anticipate that nearly 50 percent of the mammals, birds, reptiles, and other organisms found nowhere else on earth will become threatened according to the criteria of the Red List, an inventory of imperiled animals and plants maintained by the International Union for Conservation of Nature (IUCN).

The study titled "Conservation of the endemic species of the Albertine Rift under future climate change" appears in the online version of the journal Biological Conservation. The authors are: S. Ayebare, D. Kujirakwinja, D. Segan of WCS; and A.J. Plumptre of WCS and the Conservation Science Group in Cambridge, United Kingdom.

"Much of the Albertine Rift is mountainous terrain, and the species that inhabit these places have narrow ranges," said WCS scientist Dr. Andrew Plumptre, one of the authors of the study. "This makes many species especially vulnerable to climate change. Using distribution models to predict how ranges will shift as climate and precipitation levels change provide us with the means to determine how well existing protected areas will safeguard wildlife into the future."

The Albertine Rift encompasses parts of five countries (Uganda, Democratic Republic of Congo, Rwanda, Burundi, and Tanzania) and stretches from the southern tip of Lake Tanganyika to the northern tip of Lake Albert.

Using data from several sources on 162 terrestrial animals and plants unique (endemic) to the Albertine Rift, the researchers used ecological niche modeling (computer models) to determine the extent of habitat already lost due to agriculture, and to estimate the future loss of habitat as a result of climate change. On average 38 percent of suitable habitat has already been lost to agriculture in this region, where some of the highest human population densities occur in Africa.

One positive finding of the ecological niche modelling study is that while the ranges of many species are expected to contract, much of the remaining suitable habitat for many species will be located within existing protected areas, and that the recent creation of new reserves such as Itombwe and Kabobo in the Democratic Republic of Congo, have greatly increased the protection of some species under threat by future climate change. It is estimated that nearly 68 percent of the areas where current and future habitat will overlap is already safeguarded by parks and reserves.

Projecting forward, the research team anticipate that the ranges of many species will shift to higher elevations as changing environmental conditions envelop the landscapes of the Albertine Rift. The study models predicted that, on average, a shocking 75 percent of all remaining suitable habitat across all species examined would disappear by the year 2080. By that time, only an average of 15.5 percent of the original suitable habitat of the mammals, birds, and other endemic species of the Albertine Rift would remain. The most extreme forecasts--the loss of more than 90 percent of all remaining habitat--is expected to imperil 34 of the rift's endemic species.

"We hope that this study and similar ones will help wildlife managers and government agencies to anticipate where conservation measures to protect the region's unique primates, such as the mountain and Grauer's gorillas, birds, reptiles, and other unique species will be most effective," said Sam Ayebare of WCS Uganda and lead author of the paper.

A recent study by George Mason University researchers in the Department of Global and Community Health found that women who have given birth have shorter telomeres compared to women who have not given birth. Telomeres are the end caps of DNA on our chromosomes, which help in DNA replication and get shorter over time. The length of telomeres has been associated with morbidity and mortality previously, but this is the first study to examine links with having children.

Their findings were published in Human Reproduction. The authors reported that telomeres among women who had children were the equivalent of 11 years shorter. This was a larger change than has been reported by other research groups for smoking or obesity. Dr. Anna Z. Pollack, lead author of the study, pointed out, "with cross-sectional data, we can't tell if having children is related to shortening of telomeres or merely whether women who have children start out with shorter telomeres." Additional factors to consider include stress and social support, as well as whether similar findings are seen in men.

The paper utilized data from the National Health and Nutrition Examination Survey, which is a nationally representative study in the United States. Pollack notes that these findings, "are preliminary and should be confirmed with prospective studies." The study was co-authored by Mason alumna, Kelsey Rivers, who completed the research study through a George Mason University Undergraduate Research Scholars Program award.

In a new study in Nature Neuroscience, Jaideep Bains, PhD, and his team at the Cumming School of Medicine's Hotchkiss Brain Institute (HBI), at the University of Calgary have discovered that stress transmitted from others can change the brain in the same way as a real stress does. The study, in mice, also shows that the effects of stress on the brain are reversed in female mice following a social interaction. This was not true for male mice.

"Brain changes associated with stress underpin many mental illnesses including PTSD, anxiety disorders and depression," says Bains, professor in the Department of Physiology and Pharmacology and member of the HBI. "Recent studies indicate that stress and emotions can be 'contagious'. Whether this has lasting consequences for the brain is not known."

The Bains research team studied the effects of stress in pairs of male or female mice. They removed one mouse from each pair and exposed it to a mild stress before returning it to its partner. They then examined the responses of a specific population of cells, specifically CRH neurons which control the brain's response to stress, in each mouse, which revealed that networks in the brains of both the stressed mouse and naïve partner were altered in the same way.

The study's lead author, Toni-Lee Sterley, a postdoctoral associate in Bains' lab said, "What was remarkable was that CRH neurons from the partners, who were not themselves exposed to an actual stress, showed changes that were identical to those we measured in the stressed mice."

Next, the team used optogenetic approaches to engineer these neurons so that they could either turn them on or off with light. When the team silenced these neurons during stress, they prevented changes in the brain that would normally take place after stress. When they silenced the neurons in the partner during its interaction with a stressed individual, the stress did not transfer to the partner. Remarkably, when they activated these neurons using light in one mouse, even in the absence of stress, the brain of the mouse receiving light and that of the partner were changed just as they would be after a real stress.

The team discovered that the activation of these CRH neurons causes the release of a chemical signal, an 'alarm pheromone', from the mouse that alerts the partner. The partner who detects the signal can in turn alert additional members of the group. This propagation of stress signals reveals a key mechanism for transmission of information that may be critical in the formation of social networks in various species.

Another advantage of social networks is their ability to buffer the effects of adverse events. The Bains team also found evidence for buffering of stress, but this was selective. They noticed that in females the residual effects of stress on CRH neurons were cut almost in half following time with unstressed partners. The same was not true for males.

Bains suggests that these findings may also be present in humans. "We readily communicate our stress to others, sometimes without even knowing it. There is even evidence that some symptoms of stress can persist in family and loved ones of individuals who suffer from PTSD. On the flip side, the ability to sense another's emotional state is a key part of creating and building social bonds."

This research from the Bains lab indicates that stress and social interactions are intricately linked. The consequences of these interactions can be long-lasting and may influence behaviours at a later time.

BIRMINGHAM, Ala. - Extremely low birth-weight babies are at risk for a chronic lung disease called bronchopulmonary dysplasia, or BPD. This condition can lead to death or long-term disease, but clinical measurements are unable to predict which of the tiny infants -- who get care in hospital intensive-care units and often weigh just one and a half pounds -- will develop BPD.

University of Alabama at Birmingham researchers now report discovery of a strong predictive biomarker for BPD, and they show a role for the biomarker in the pathogenesis of this neonatal lung disease. These results open the path to possible future therapies to prevent or lessen BPD, which is marked by inflammation and impaired lung development.

This biomarker could also help neonatologists plan optimal management and risk stratification of their tiny patients, and it could guide targeted enrollment of high-risk infants into randomized trials of potentially novel treatment strategies.

The UAB work, published in the journal JCI Insight, is an example of "bedside to bench" research. It began with prospective studies of extremely premature infants to identify potential biomarkers, and then proceeded to lab experiments using animal models and cells grown in culture to learn how the biomarker functions in disease progression.

The study was led by Charitharth Vivek Lal, M.D., assistant professor in the UAB Pediatrics Division of Neonatology, and it builds upon Lal's 2016 report that early microbial imbalance in the airways of extremely premature infants is predictive for development of BPD.

The biomarker in the JCI Insight study is microRNA 876-3p.

Study details

The hunt for the biomarker began with a prospective cohort study at the UAB Regional Neonatal Intensive Care Unit, looking at exosomes obtained from tracheal aspirates of infants with severe BPD, compared with full-term controls. Exosomes are small, membrane-bound blebs or vesicles that are actively secreted by a variety of cells. They are known to contain microRNAs and proteins, and the exosomes act in cell-to-cell signaling. MicroRNAs can regulate gene expression in cells.

Lal and colleagues found that airway cells in infants with severe BPD had greater numbers of exosomes, but those exosomes were smaller sized. They also experimentally found that high oxygen exposure for newborn mice or human bronchial epithelial cells grown in culture also caused the release of more exosomes, and the exosomes were smaller in size that those secreted at normal oxygen level. Premature infants often receive extra oxygen to aid their underdeveloped lungs.

The UAB researchers then did a prospective discovery cohort study at UAB -- they collected tracheal aspirate samples from extremely premature infants within six hours of birth, purified exosomes from the samples and looked for microRNAs in the exosomes. Out of 810 microRNAs that were found, 40 showed differences between infants who later developed BPD and those who were BPD-resistant.

Next, in cooperation with researchers at Thomas Jefferson University and Drexel University, a validation cohort was studied in Philadelphia. Thirty-two of the 40 microRNAs were confirmed; six had a higher statistical significance; and one biomarker, a low concentration of microRNA 876-3p, was found to have the highest sensitivity to predict severe BPD in extremely low birth-weight infants.

The researchers then showed changes in expression of microRNA 876-3p in BPD in three types of experiments. First, tracheal-aspirate, exosomal microRNA 876-3p expression was decreased in infants with severe BPD, as compared with full-term infant controls.

Second, using an animal model of BPD where mouse pups are exposed to high levels of oxygen, microRNA 876-3p expression from exosomes in bronchoalveolar lavage fluid was found to progressively decrease over 10 days of oxygen exposure. At the same time, the gene expression of two targets of microRNA 876-3p increased.

Third, exosomal microRNA 876-3p was decreased in supernatants of normal human bronchial epithelial cells exposed to high levels of oxygen for 24 hours, another model for BPD. This was accompanied by higher gene expression of the two targets of the microRNA. Experimental addition of a mimic of microRNA 876-3p, which causes gain of function, increased the expression of microRNA 876-3p and reduced the expression of the two targets.

Since Lal and colleagues had previously shown presence of increased Proteobacteria in the airways of infants with severe BPD, they tested the effect of adding Proteobacteria lipopolysaccharide, or LPS, to the animal and cell culture models of BPD. In both models, LPS alone had an effect similar to high levels of oxygen. When LPS and high oxygen were used together in double-injury tests, the researchers found even greater decrease in exosomal microRNA 876-3p; in the animal model, the double injury caused greater impairment of lung development and higher expression of inflammatory cytokines than either high oxygen or LPS alone.

Finally, the researchers tested the effect of giving a gain-of-function mimic of microRNA 876-3p to pups in the animal model of BPD. For both the high-oxygen model and the double-injury model of high oxygen and LPS, mice given the mimic showed protection as measured by less alveolar hypoplasia and decreased neutrophilic inflammation.

"These data establish that exosomal microRNAs have critical and causative roles in neonatal chronic lung disease pathogenesis," Lal said.

A new study reveals that acetaminophen use and over-dosing rise in cold/flu season in the United States, primarily due to increased use of over-the-counter combination medications treating upper respiratory symptoms. Another study reports that acetaminophen is the most commonly used analgesic in France, with more high-dose tablets being consumed in recent years. The findings, which are published in the British Journal of Clinical Pharmacology, indicate that individuals should take special care to follow labeled dosing directions for acetaminophen-containing products.

Acetaminophen is an active ingredient present in hundreds of over-the-counter and prescription medications indicated for pain and fever, including medications used to treat symptoms associated with colds, flu, allergies, and sleeplessness. While safe when taken as directed, taking too much acetaminophen can harm the liver. To examine acetaminophen use and to estimate the prevalence of excess intake, a team led by Saul Shiffman, PhD, of Pinney Associates and the University of Pittsburgh, and David Kaufman, ScD, of Boston University Slone Epidemiology Center, asked individuals to complete daily medication diaries for 7 days. For the study, 14,481 US adults who used acetaminophen in the preceding 30 days were sampled from multiple online research panels from 2011 to 2016.

The investigators found that 6.3% of acetaminophen users exceeded the maximum adult daily dose of 4 grams (4000 mg) on at least one day during a week they used acetaminophen. All told, the 4 gram limit was exceeded on 3.7% of the days that the participants used acetaminophen medications. Use patterns changed with the cold/flu season. Cold/flu symptoms were more likely to be experienced and treated with acetaminophen-containing medications during cold/flu season. The odds of taking more than 4 grams of acetaminophen in a day increased 24% in cold/flu season compared with the off-season (6.5% during cold/flu season versus 5.3% during the off-season). This was primarily due to increased use of over-the-counter combination medications designed to treat upper respiratory cold/flu symptoms.

"This is the first multi-year, year-round study that includes detailed data on how consumers used acetaminophen medications," said Dr. Shiffman. "The study findings suggest the importance of educating consumers about acetaminophen and counseling them about appropriate use and safe dosages of these medications." Dr. Shiffman noted that Johnson and Johnson Consumer, which sponsored the study, has used these findings to develop education for both patients/a> and health professionals. "Getting this message out is especially important during cold/flu season, when people may be more likely to treat illness symptoms with acetaminophen combination products, sometimes without even realizing they contain acetaminophen," Dr. Shiffman stressed. "As we are in the midst of a particularly severe cold/flu season, it's important for consumers to be aware of the limits on acetaminophen use."

Another study that examined trends in the use of pain medications in France found that over the last decade, acetaminophen--also known as paracetamol--remained the most-consumed analgesic in the country, while the use of oxycodone (an opioid) increased significantly.

"To our knowledge, this is the first published study analysing consumption trends for both non-opioids and opioids over the last decade in France. Long-term surveillance over the past 10 years has highlighted quantitative and qualitative changes in analgesic consumption patterns in France," said co-author Philippe Cavalié, PhD, of the French National Agency for Medicines and Health Products Safety.

There was a 53% increase in the use of paracetamol between 2006 and 2015, and the 1000-mg tablets of paracetamol (which are not available in the United States) were the most-used drug among adults since 2008. Their consumption increased over the 10-year period by 140%, whereas consumption of the 500-mg tablet pack decreased by 20%.

Also, despite sharing common regulations for medications, different patterns of pain medication use were observed across Europe in 2015. France ranked first and third place respectively for paracetamol and mild opioid consumption, but its use of strong opioids was among the lowest.

"The very widespread analgesics consumption that we have documented raises the concern of overuse and misuse, as well as addiction to opioids," said Dr. Cavalié. "It appears very useful to accurately monitor user profiles and trends of misuse and to carry out appropriate preventive measures--such as education of patients and health professionals to increase appropriate use of medications and early detection of misuse."

Massachusetts boasts one of the most iconic fisheries in the U.S., but new research suggests that protecting marine coastlines has surpassed commercial fishing as an economic driver.

The study is the first to calculate the economic value of coastal preservation in Massachusetts. The research finds these efforts contributed $179 million to the state's economy in 2014, more than finfish landings ($105 million) and whale-watching ($111 million).

"Marine conservation has become a major economic force in Massachusetts," says lead author Joe Roman, a University of Vermont (UVM) biologist. "For the first time, this study gives us the tools to properly capture the magnitude of this value.

After years of diminishing catches of wild fish - including cod, haddock and flounder - finfish landings have also been surpassed by commercial shellfish operations ($420 million) and recreational fishing ($688.5 million).

The study, by a team of economists and marine experts from UVM, Boston University and Franklin Pierce University, was published today in the journal Frontiers in Ecology and the Environment.

NEW TOOL FOR MEASURING CITIZENS’ VALUE OF NATURE

To calculate marine stewardship’s $179-million value, researchers pioneered a new method to account for the millions in donations and volunteer time flowing to marine conservation nonprofit organizations.

Of Massachusetts philanthropy in 2014, researchers determined that coastal stewardship groups received more than $122 million in monetary donations, and $57 million worth of volunteer time.

The findings are conservative. The team found that environmental groups with a partial marine mission had a greater value – $282 million in 2014 – but chose to focus on organizations primarily addressing coastal ecosystems. They also excluded university programs, direct spending by government agencies (other than select programs or grants), and money from companies for conservation.

Coastal conservation groups support a range of activities, including responses to marine mammal strandings, cleanup of beaches and waterways, marsh and dune restoration, and education and public-awareness campaigns.

“These organizations provide jobs, and the money they raise is often spent on local goods and services,” says co-author Brendan Fisher of UVM’s Gund Institute for Environment and Rubenstein School of Environment and Natural Resources. “And the results of conservation efforts can benefit many people.”

IMPLICATIONS FOR GOVERNMENT

The importance of coastlines - in Massachusetts and elsewhere - are no secret. Nice beaches and harbors attract tourists. Flourishing sea life contributes to cleaner water and more food options. Plenty of people care about the welfare of marine mammals and the quality of the world's oceans.

But quantifying how humans value the environment can be challenging. Business sectors can often dominate policy and regulation discussions, as a result, Roman says.

By highlighting the economic might of marine conservation, Roman hopes to show that environmental groups deserve a place at the table when discussing Massachusetts' ocean economy. "Having better data will help policy makers understand the trade-offs and make better decisions."

While some researchers have conducted surveys to determine how much someone is "willing to pay" to save a humpback whale, those numbers don't require real dollars and sometimes overstate the actual expenditures for such efforts, Roman notes.

AN 'AHA MOMENT' IN CAPE COD

The idea for the study struck Roman on a class trip to Cape Cod to explore the trade-offs of a proposed offshore wind farm. The group met with commercial fishermen, wind developers, conservationists and an oyster farmer.

One morning, his UVM class discovered five dolphins stranded on a beach in Wellfleet, Mass. They watched as the marine stranding experts cared for the mammals' health and released them back into the ocean.

"People had tears in their eyes when they were releasing the dolphins," says Roman, who noticed the workers and volunteers who responded to the stranding. He started counting up the investments in time, equipment and money.

"We're ignoring this whole part of the economy," he thought.

Roman says the valuation could easily apply to other parts of the U.S. coastline - along the Gulf or Pacific Ocean, for example - with adjustments made for the conservation work that's most relevant in each location. Efforts to save sea turtles, for example, are significant in North Carolina.

"As we're making decisions about the future of our oceans," Roman says, "let's make sure stewardship has a role."

A newly-discovered hereditary mutation is responsible for an increased production of erythropoietin (EPO) in the blood. This mutation causes a messenger RNA (mRNA) that is not normally involved in the formation of proteins to be reprogrammed so that it produces EPO, thus abnormally increasing the number of red blood cells. Researchers from the Department of Biomedicine at the University of Basel and University Hospital Basel reported these findings in The New England Journal of Medicine.

In patients suffering from erythrocytosis, the red blood cell mass (erythrocytes) is exceptionally high. The disease is usually triggered by a genetic disorder in the bone marrow, which leads to increased production of red blood cells.

Researchers from the University of Basel and University Hospital Basel have now identified the first mutation in the EPO gene in a family with hereditary erythrocytosis. Ten affected family members from four generations took part in the study.

Using a genome-wide linkage analysis and gene sequencing, the researchers discovered that all of the affected family members lacked a single base in the EPO gene. As the EPO hormone increases the production of red blood cells, it was likely that this mutation caused the disease.

Overproduction instead of failure

However, the researchers were initially puzzled. This mutation would actually lead to a loss of function of the EPO gene, because the absence of the base shifts the reading frame of the genetic code, meaning that no more EPO protein can be formed. Despite this, the concentration of EPO hormone in the patients' blood measurably increased rather than decreased.

The explanation was found using the CRISPR method, which allowed the researchers to engineer cells carrying the EPO mutation. There is a second, hidden mRNA in the EPO gene that is not normally involved in the production of a protein. As the researchers show, the mutation also leads to a shift in the reading frame of this second mRNA, this time with the result that more biologically active EPO hormone is produced.

"The mechanism is intriguing," says study leader Professor Radek Skoda from the University of Basel's Department of Biomedicine. "The mutation reprograms the gene product so that it gains a new function and is misused to overproduce EPO." With consequences for the patients, who suffer from headaches and dizziness thanks to the increased red blood mass.

Mutations in the EPO gene should be taken into account in future searches for the causes of hereditary erythrocytosis, write the researchers in The New England Journal of Medicine.

Watching YouTube videos, Instagram demos, and Facebook tutorials may make us feel as though we're acquiring all sorts of new skills but it probably won't make us experts, according to research published in Psychological Science, a journal of the Association for Psychological Science.

"The more that people watched others, the more they felt they could perform the same skill, too--even when their abilities hadn't actually changed for the better," says study author Michael Kardas of The University of Chicago Booth School of Business. "Our findings suggest that merely watching others could cause people to attempt skills that they might not be ready or able to perform themselves."

Social media platforms have made it easy to record, share, and access instructional videos. But does watching videos without practicing the demonstrated skills actually improve our ability to perform them? Kardas and coauthor Ed O'Brien conducted a series of six experiments to find out.

In one online experiment, the researchers assigned 1,003 participants to watch a video, read step-by-step instructions, or merely think about performing the "tablecloth trick," which involves pulling a tablecloth off a table without disturbing the place settings on top. People who watched the 5-second video 20 times were much more confident in their ability to pull off the trick than were those who watched the video once. However, people who simply read or thought about the trick for an extended period of time did not show this confidence boost. These results provided initial evidence that repeated viewing may lead people to an inflated sense of competence.

To find out whether this perception is borne out by actual performance, Kardas and O'Brien tested a group of 193 participants on their dart-throwing abilities. Those who watched a demo video 20 times estimated that they would score more points than those who saw the video only once--this high-exposure group also predicted that they would be more likely to hit the bull's-eye and reported that they had learned more technique and improved more after watching the video.

But these perceptions did not line up with reality: People who watched the video many times scored no better than those who saw it once.

Kardas and O'Brien found evidence for this phenomenon in other domains, including doing the moonwalk, playing a digital computer game, and juggling. The more that participants watched others perform these skills, the more they overestimated their own abilities.

Why does repeatedly watching a video breed such overconfidence? Participants who watched a variation of the tablecloth trick video that did not show the performer's hands evidenced no exposure-related overconfidence, suggesting that people may feel confident only when they can track the specific steps and actions in performing a skill.

Thinking about detailed steps or learning technical information about the objects involved did not lead participants to form more accurate perceptions. In an experiment focused on juggling, only participants who were able to hold the pins after watching a juggling video revised their estimates, reporting that they had learned less and were less capable than they originally thought after watching.

"We see this as a potentially widespread phenomenon given that people have daily access to outlets for watching others perform," says Kardas. "Anyone who goes online to look up tips before attempting a skill -- from cooking techniques to DIY home repairs to X Games tricks -- would benefit from knowing that they might be overconfident in their own abilities after watching, and should exercise caution before attempting similar skills themselves."

The researchers are interested in testing other strategies--such as playing virtual-reality games--that might mitigate the overconfidence effect, helping people to better appreciate the limitations inherent in merely watching others.

Farm manure could be a viable source of renewable energy to help reduce greenhouse gas emissions that cause global warming.

Researchers at the University of Waterloo are developing technology to produce renewable natural gas from manure so it can be added to the existing energy supply system for heating homes and powering industries. That would eliminate particularly harmful gases released by naturally decomposing manure when it is spread on farm fields as fertilizer and partially replace fossil natural gas, a significant contributor to global warming.

"There are multiple ways we can benefit from this single approach," said David Simakov, a professor of chemical engineering at Waterloo. "The potential is huge."

Simakov said the technology could be viable with several kinds of manure, particularly cow and pig manure, as well as at landfill sites.

In addition to being used by industries and in homes, renewable natural gas could replace diesel fuel for trucks in the transportation sector, a major source of greenhouse gas emissions.

To test the concept, researchers built a computer model of an actual 2,000-head dairy farm in Ontario that collects manure and converts it into biogas in anaerobic digesters. Some of that biogas is already used to produce electricity by burning it in generators, reducing the environmental impact of manure while also yielding about 30 to 40 percent of its energy potential.

Researchers want to take those benefits a significant step further by upgrading, or converting, biogas from manure into renewable natural gas. That would involve mixing it with hydrogen, then running it through a catalytic converter. A chemical reaction in the converter would produce methane from carbon dioxide in the biogas.

Known as methanation, the process would require electricity to produce hydrogen, but that power could be generated on-site by renewable wind or solar systems, or taken from the electrical grid at times of low demand. The net result would be renewable natural gas that yields almost all of manure's energy potential and also efficiently stores electricity, but has only a fraction of the greenhouse gas impact of manure used as fertilizer.

"This is how we can make the transition from fossil-based energy to renewable energy using existing infrastructure, which is a tremendous advantage," said Simakov, who collaborates with fellow chemical engineering professor Michael Fowler.

The modelling study showed that a $5-million investment in a methanation system at the Ontario farm would, with government price subsidies for renewable natural gas, have about a five-year payback period.

A paper on modelling of a renewable natural gas generation facility at the Ontario farm, which also involved a post-doctoral researcher and several Waterloo students, was recently published in the International Journal of Energy Research.

New Rochelle, NY, March 7, 2018--Researchers have shown that a wide variety of synthetic antisense oligonucleotides with different chemical modifications can activate the frataxin gene, which contains a mutation that decreases its expression in the inherited neurologic disorder Friedreich's ataxia (FA). This new finding, which demonstrates a broad range of flexible options for identifying novel compounds capable of increasing frataxin protein expression and alleviating the effects of FA, is published in Nucleic Acid Therapeutics, a peer-reviewed journal from Mary Ann Liebert, Inc. publishers. The article is available free on the Nucleic Acid Therapeutics website until April 7, 2018.

The article entitled "Activation of Frataxin Protein Expression by Antisense Oligonucleotides Targeting the Mutant Expanded Repeat" is coauthored by David Corey UT Southwestern Medical Center at Dallas, TX and coauthors from Ionis Pharmaceuticals (Carlsbad, CA), McGill University (Montreal, Canada), and University of Massachusetts (Worcester, MA). The researchers show that various nucleic acid compounds with a range of chemical modifications are able to bind to the abnormal GAA repeat sequences in the FA gene. They demonstrated this in multiple cell lines derived from FA patients who had varied numbers of GAA repeats, implying a strong foundation for future drug development.

"The resources and long-term commitment required to pursue these types of investigations underline the needs and benefits of academia-industry collaborations that are advancing the field," says Executive Editor Graham C. Parker, PhD, The Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Children's Hospital of Michigan, Detroit, MI.

Research reported in this publication was supported by the National Institutes of Health under Award Number GM R35118103. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.