Culture

STRASBURG, PA- A new study analyzes 30 years of patient data and details the clinical course of 184 individuals with genetically diverse forms of Maple Syrup Urine Disease (MSUD), which is among the most volatile and dangerous inherited metabolic disorders. Researchers collected data on survival, hospitalization rates, metabolic crises, liver transplantation, and cognitive outcome. This represents the largest systematic study of MSUD, with regard to both cohort size and the duration of clinical follow up. The study was a broad collaborative effort led by clinicians and researchers at the Clinic for Special Children (CSC) and will appear in Molecular Genetics and Metabolism.

Before the CSC's inception, one in three children born with MSUD died from neurological complications of the disease before 10 years of age, and the majority of survivors were permanently disabled. Three decades of innovation and clinical care by the CSC team have increased survival from 63% to 95% while hospitalization rates have decreased from 7 to just 0.25 hospital days per patient per year. Specific advances in management include new prescription formulas for children and adults as well as elective liver transplantation, a collaboration with the Hillman Center for Pediatric Transplantation (UPMC Children's Hospital of Pittsburgh) that has been 100% successful for 93 individuals transplanted since 2003.

Treatment of MSUD requires close monitoring of blood amino acid levels. A total of 13,589 amino acid profiles were generated by CSC's on-site clinical laboratory and the data were analyzed to determine the overall effectiveness of treatment. The authors conclude that although stringent dietary therapy maintains blood amino acid concentrations within acceptable limits, it is challenging to implement, especially for individuals older than 10 years of age, and does not fully prevent the cognitive and psychiatric disabilities caused by MSUD.

Eighty-two (82) MSUD patients underwent IQ testing, with higher IQ scores correlating by age with younger patients. On average, MSUD patients scored 23% lower on IQ testing than their unaffected siblings and, as compared to the general population, the prevalence of affective illness (depression, anxiety, and panic disorder) was much higher among both MSUD patients and their unaffected siblings. Based on these observations, the authors conclude that despite advances in clinical care, MSUD remains a morbid and potentially fatal disorder, and there remains a critical unmet need for safer and more effective disease-modifying interventions, including gene replacement or editing therapies.

Children as young as 6 years old who underwent fetal surgery to repair a common birth defect of the spine are more likely to walk independently and have fewer follow-up surgeries, compared to those who had traditional corrective surgery after birth, according to researchers funded by the National Institutes of Health. Their study appears in Pediatrics.

The procedure corrects myelomeningocele, the most serious form of spina bifida, a condition in which the spinal column fails to close around the spinal cord. With myelomeningocele, the spinal cord protrudes through an opening in the spine and may block the flow of spinal fluid and pull the brain into the base of the skull, a condition known as hindbrain herniation.

In 2011, the Management of Myelomeningocele study, funded by NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), found that by 12 months of age, children who had fetal surgery required fewer surgical procedures to divert, or shunt, fluid away from the brain. By 30 months, the fetal surgery group was more likely to walk without crutches or other devices.

For the current study, NICHD-funded researchers re-evaluated children from the original trial when they were 6 to 10 years old. Of the 161 children who took part in the follow-up study, 79 had been assigned to prenatal surgery and 82 had been assigned to traditional surgery. Children in the prenatal surgery group walked independently more often than those in the traditional surgery group (93% vs. 80%). Those in the prenatal surgery group also had fewer shunt placements for hydrocephalus, or fluid buildup in the brain (49% vs. 85%), and fewer shunt replacements (47% vs. 70%). The group also scored higher on a measure of motor skills.

The two groups did not differ significantly in a test measuring communication ability, daily living skills, and social interaction skills.

"Prenatal surgery for myelomeningocele carries benefits and risks, compared to traditional postnatal surgery," said Menachem Miodovnik, M.D., of the NICHD Pregnancy and Perinatology Branch. "This study provides important information for physicians with patients who are considering prenatal surgery."

Jan. 24, 2020--Changes in the lung microbiome may help predict how well critically ill patients will respond to care, according to new research published online in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.

Specifically, according to the authors of "Lung Microbiota Predict Clinical Outcomes in Critically Ill Patients," patients with higher levels of lung bacteria one day after admission to the ICU had fewer ventilator-free days, a strong effect that was not explained by severity of critical illness or the presence of pneumonia.

The identity of lung microbiota - which bacteria were detected - was also predictive of ICU outcomes in these patients. Two bacteria normally found in the gut -- Lachnospiraceae and Enterobacteriaceae spp -- were common in the lung microbiome of patients who had worse ICU outcomes.

The presence of Enterobacteriaceae spp in the lung microbiome was also associated with acute respiratory distress syndrome, or ARDS, a life-threatening illness in which the lungs are severely inflamed.

Prior studies by this research team found that the immune function of patients with ARDS is highly variable and that the translocation of gut bacteria to the lungs may play a role in the development of ARDS. In another earlier study, the researchers showed that the lung microbiome in patients with idiopathic pulmonary fibrosis, or IPF, is also predictive of clinical outcomes.

The human microbiome comprises the genetic material of an estimated 100 trillion microbes. Bacteria is the biggest component of the microbiome, but it also includes viruses, fungi and archaea. Unlike the human genome, which is relatively static, the microbiome is altered, sometimes dramatically, by diet, disease and other factors. While the lungs have historically been considered sterile, in the past decade investigators have used DNA-based methods to reveal that the lung contain diverse and dynamic communities of bacteria.

"We already knew that lung microbiota are altered in critically ill patients, and that this disruption is associated with altered lung immunity," said lead author Robert Dickson, MD, assistant professor of pulmonary and critical care medicine and microbiology and immunology at the University of Michigan. "What the current study tells us is that this disruption of lung microbiota is clinically meaningful. In otherwise similar patients, differences in lung bacteria help explain who recovers and who doesn't."

In their study of 91 critically ill patients, the researchers controlled for disease severity and for whether the patient had pneumonia, which would increase the number of bacteria in the lung microbiome. After taking these factors into account, the associations between ventilator-free days and the bacteria level and detection of gut-associated bacteria in the lung microbiome persisted.

The investigators are encouraged that the lung microbiome may represent a novel target for preventing and treating critical illness.

"The microbiome is something we can potentially manipulate, unlike other risk factors in the ICU," said senior author Lieuwe Bos, MD, PhD, a researcher in pulmonology and critical care and pulmonologist in training at Amsterdam University Medical Center. "We can't change our patients' genes or their chronic diseases, but we can potentially change their bodies' microbiota."

Study limitations include the fact that researchers could not control for medications, including antibiotics, that the patients may have taken before being admitted to the ICU. The researchers could not determine if the gut-associated bacteria found in some patients' lung microbiome had migrated from the lower gastrointestinal tract or whether they were found in the lungs because of aspiration, the accidental inhalation of food or liquid.

The investigators say the next step for the field will be determining whether modifying these lung bacteria influences patients' outcomes. They say this task will require both prospective human studies and animal models of critical illness.

"Predicting ICU outcomes is important, but what we really want is a target for therapy," Dr. Dickson said. "We need to figure out if the lung microbiome is something we can modify, either to prevent lung injury or to help it resolve faster."

Dr. Bos added that a "take home" message of this study and the researchers' previous study on immune function in ARDS patients is that ARDS is a heterogenous disease.

"The lungs of ARDS patients are not all alike," he said. "Knowing that immune function and the microbiome differ among these patients may not only help us predict our patients' outcomes but to change them for the better."

"This study adds to growing evidence that the lung microbiome plays a key role in lung disease," said James Kiley, PhD, director of the Division of Lung Diseases at the National Heart, Lung, and Blood Institute, part of the National Institutes of Health. "It's important that we continue to explore the microbiome and other factors that contribute to lung disease and clinical outcomes."

A new study published on 24 January 2020 in the journal Toxics provides important insight into the recent lung intoxication epidemic referred to as "e-cigarette or vaping product use-associated lung injury" (EVALI). The study presents, for the first time, a comprehensive analysis of products used by EVALI patients. Vitamin E acetate was the main finding in cannabinoid liquids. No compound that could be linked to EVALI was found in the two nicotine products tested.

Researchers from the Wadsworth Center of the New York State Department of Health, the State University of New York at Albany and Albany Medical Center conducted untargeted as well as targeted analyses of 38 liquid samples reportedly used by the first ten cases of EVALI in New York State to identify potential culprits for the serious lung disease epidemic. Two of the samples were nicotine-containing liquids, while the rest were illicit cannabinoid liquids. The latter contained relatively low cannabinoid content compared with typical cannabis oil vaporizer liquids, and some had unusual Δ9-/Δ8-tetrahydrocannabinol (THC) ratios. A variety of pesticide residues, such as myclobutanil and bifenthrin, were detected in some samples. However, the most striking finding was the identification of vitamin E acetate as a major diluent in 64% of the samples, at levels ranging from 16% to 57% by mass. No unknown compound that could potentially cause EVALI was found in the two nicotine products tested.

"Our laboratory was the first to identify vitamin E acetate in vaporizer fluids recovered from pulmonary injury patients, which we promptly reported to officials of the U.S. Centers for Disease Control and Prevention (CDC), the U.S. Food and Drug Administration (FDA) and public health officials from numerous states via conference call and via e-mail on August 19, 2019," said David C. Spink, Ph.D., Chief of the Laboratory of Organic Analytical Chemistry at Wadsworth and corresponding author of the study.

"Based on our work, the New York State Department of Health issued a press release on September 5, 2019 indicating that vitamin E acetate was a key focus of the Department's investigation of potential causes of vaping-associated pulmonary illnesses. To investigate potential sources of the vitamin E acetate in the illicit vaporizer fluids, the Department purchased six products marketed as cannabis oil diluents or thickeners via the internet. Three of these were found to be essentially pure vitamin E acetate," Spink said.

According to the latest CDC data, there have been 1979 hospitalizations and 57 deaths from EVALI in the US. While the exact cause for the condition is still under investigation, there is a strong association between EVALI and the use of THC-containing vaporizer liquids, and vitamin E acetate has been found in product samples tested by the FDA and state laboratories and in bronchioalveolar lavage fluids recovered from the lungs of patients tested by the CDC. While no specific compounds present in nicotine-containing e-cigarette products have been linked to the disease, the contributing cause or causes of illness for individuals reporting use of only nicotine-containing products warrants further study.

A sustained state of vigilance will generate a different type of memory than a momentary startle, and these differences are linked to distinct signaling molecules in the brains of mice. Researchers at the RIKEN Center for Brain Science (CBS) have visualized these dynamics in the living mouse brain for the first time, observing fast and slow molecular pathways that support memory function. These processes take place in brain cells called astrocytes, revealing another important way in which these cells help neurons.

Norepinephrine, also called noradrenaline, is a dual hormone and neurotransmitter that prepares the body for action. Previous research has shown that norepinephrine release is important for modifying synapses, the connections between neurons that form and consolidate memories. Astrocytes are the crucial mediators of these changes, and the researchers were interested in observing, in real time, what happens in these cells when mice are learning. Their study was published in Nature Communications on January 24.

First, the team artificially stimulated brain cells with light, a method called optogenetics, to induce norepinephrine release. They focused on noradrenergic neurons originating in a part of the brain called the locus coeruleus. Norepinephrine release launched two distinct chains of molecular events, the first involving calcium activity and the second cAMP, an important signaling molecule. Calcium levels in astrocytes were quick to become elevated following norepinephrine release, while cAMP levels had a slower but more sustained increase. "We think these fast and slow dynamics are significant because calcium elevation in astrocytes promotes synaptic plasticity, or the ability of cells to form new memory connections, while cAMP elevation mobilizes energy metabolism for memory consolidation," said Hajime Hirase, senior author and team leader at RIKEN CBS.

To see how these fast and slow molecular responses are triggered naturally, mice were given random air puffs to the face to evoke a brief startle response. In this situation, cAMP levels did not go up at all, while calcium became elevated as previously observed. In a second experiment, mice were given a foot shock coupled with a sound to create a fear memory. When they heard the sound again, the mice would freeze in anticipation of a shock. This time, cAMP levels were noticeably elevated, while calcium levels also rose but quickly tapered off. "When mice are in this sustained state of vigilance, a lot of norepinephrine is released, coupled with gradually building cAMP," explains first author Yuki Oe, a research scientist in Hirase's group. "This reflects how the astrocytes support the formation of fear memory." Neither calcium nor cAMP responses were seen in mice that were given norepinephrine-blocking drugs, indicating that norepinephrine release is indeed the trigger for these changes.

The short-term and long-term consequences of norepinephrine release in the brain thus depend on the situation and behavior. Memory formation, in particular, seems to be supported by increases in cAMP levels, while transient or low vigilance states involve short-term elevated calcium. "One of the effects of cAMP is to break down glycogen for quick energy in a fight-or-flight situation," comments Hirase. "This boosting of energy metabolism could help consolidate memories over longer time scales, while rapid calcium boosts could lower the threshold for synaptic plasticity."

A remarkable new species of meat-eating dinosaur has been unveiled at the Natural History Museum of Utah. Paleontologists unearthed the first specimen in early 1990s in Dinosaur National Monument in northeastern Utah. The huge carnivore inhabited the flood plains of western North America during the Late Jurassic Period, between 157-152 million years ago, making it the geologically oldest species of Allosaurus, predating the more well-known state fossil of Utah, Allosaurus fragilis. The newly named dinosaur Allosaurus jimmadseni, was announced today in the open-access scientific journal PeerJ.

The species belongs to the allosauroids, a group of small to large-bodied, two-legged carnivorous dinosaurs that lived during the Jurassic and Cretaceous periods. Allosaurus jimmadseni, possesses several unique features, among them a short narrow skull with low facial crests extending from the horns in front of the eyes forward to the nose and a relatively narrow back of the skull with a flat surface to the bottom of the skull under the eyes. The skull was weaker with less of an overlapping field of vision than its younger cousin Allosaurus fragilis. Allosaurus jimmadseni evolved at least 5 million years earlier than fragilis, and was the most common and the top predator in its ecosystem. It had relatively long legs and tail, and long arms with three sharp claws. The name Allosaurus translates as "different reptile," and the second part, jimmadseni, honors Utah State Paleontologist James H. Madsen Jr.

Following an initial description by Othniel C. Marsh in 1877, Allosaurus quickly became the best known--indeed the quintessential--Jurassic theropod. The taxonomic composition of the genus has long been a debate over the past 130 years. Paleontologists argue that there are anywhere between one and 12 species of Allosaurus in the Morrison Formation of North America. This study recognizes only two species--A. fragilis and A. jimmadseni.

"Previously, paleontologists thought there was only one species of Allosaurus in Jurassic North America, but this study shows there were two species--the newly described Allosaurus jimmadseni evolved at least 5 million years earlier than its younger cousin, Allosaurus fragilis," said co-lead author Mark Loewen, research associate at the Natural History Museum of Utah, and associate professor in the Department of Geology and Geophysics at the University of Utah led the study. "The skull of Allosaurus jimmadseni is more lightly built than its later relative Allosaurus fragilis, suggesting a different feeding behavior between the two."

"Recognizing a new species of dinosaur in rocks that have been intensely investigated for over 150 years is an outstanding experience of discovery. Allosaurus jimmadseni is a great example of just how much more we have to learn about the world of dinosaurs. Many more exciting fossils await discovery in the Jurassic rocks of the American West," said Daniel Chure, retired paleontologist at Dinosaur National Monument and co-lead author of the study.

George Engelmann of the University of Nebraska, Omaha initially discovered the initial skeleton of the new species within Dinosaur National Monument in 1990. In 1996, several years after the headless skeleton was collected, the radioactive skull belonging to the skeleton using a radiation detector by Ramal Jones of the University of Utah. Both skeleton and skull were excavated by teams from Dinosaur National Monument.

"Big Al," another specimen belonging to the new species, was discovered in Wyoming on United States Bureau of Land Management (BLM) land in 1991 and is housed in the collections of the Museum of The Rockies in Bozeman, Montana. Previously thought to belong to Allosaurus fragilis, "Big Al" was featured in the BBC's 2001 "Walking with Dinosaurs: Ballad of Big Al" video. Over the last 30 years, crews from various museums have collected and prepared materials of this new species. Other specimens include "Big Al Two" at the Saurier Museum Aathal in Switzerland and Allosaurus material from the Dry Mesa Quarry of Colorado at Brigham Young University.

"This exciting new study illustrates the importance of continued paleontological investigations on public lands in the West. Discovery of this new taxon of dinosaur will provide important information about the life and times of Jurassic dinosaurs and represents another unique component of America's Heritage," said Brent Breithaupt, BLM regional paleontologist.

Early Morrison Formation dinosaurs were replaced by some of the most iconic dinosaurs of the Late Jurassic

Allosaurus jimmadseni lived on the semi-arid Morrison Formation floodplains of the interior of western North America. The older rocks of the Morrison Formation preserve a fauna of dinosaurs distinct from the iconic younger Morrison Formation faunas that include Allosaurus fragilis, Diplodocus and Stegosaurus. Paleontologists have recently determined that specimens of this new species of dinosaur lived in several places throughout the western interior of North America (Utah, Colorado and Wyoming).

Study summary

Dinosaurs were the dominant members of terrestrial ecosystems during the Mesozoic. However, the pattern of evolution and turnover of ecosystems during the middle Mesozoic remains poorly understood. The authors report the discovery of the earliest member of the group of large-bodied allosauroids in the Morrison Formation ecosystem that was replaced by Allosaurus fragilis and illustrate changes acquired in the genus over time. The study includes an in-depth description of every bone of the skull and comparisons with the cranial materials of other carnivorous dinosaurs. Finally, the study recognizes just two species of Allosaurus in North America with Allosaurus fragilis replacing its earlier relative Allosaurus jimmadseni.

Fact sheet: Major points of the paper

A remarkable new species of meat-eating dinosaur, Allosaurus jimmadseni, is described based on two spectacularly complete skeletons. The first specimen was unearthed in Dinosaur National Monument, in northeastern Utah.

Allosaurus jimmadseni is distinguished by a number of unique features, including low crests running from above the eyes to the snout and a relatively narrow back of the skull with a flat surface to the bottom of the upper skull under the eyes. The skull was weaker with less of an overlapping field of vision than its younger cousin Allosaurus fragilis.

At 155 million years old, Allosaurus jimmadseni is the geologically-oldest species of Allosaurus predating the more well-known State Fossil of Utah Allosaurus fragilis.

Allosaurus jimmadseni was the most common and the top predator in its ecosystem. It had relatively long legs and tail, and long arms with three sharp claws.

Study design

Comparison of the bones with all other known allosauroid dinosaurs indicate that the species possessed unique features of the upper jaw and cheeks (maxilla and jugal) and a decorative crest stretching from just in front of the eyes to the nose.

Many of the comparisons were made with the thousands of bones of Allosaurus fragilis collected from the famous Cleveland-Lloyd Dinosaur Quarry administered by the Bureau of Land Management that are housed in the collections of the Natural History Museum of Utah.

On the basis of these features, the scientific team named it a new genus and species of dinosaur, Allosaurus jimmadseni (translating to "Jim Madsen's different reptile").

Allosaurus jimmadseni is particularly notable for its slender, narrow skull with short sharp nasal crests compared to its close relative and successor Allosaurus fragilis.

The study was funded in part by the University of Utah, the National Park Service and the National Science Foundation.

New dinosaur name: Allosaurus jimmadseni

The first part of the name, Allosaurus, (a·luh·SAW·ruhs) can be translated from Greek as the "other", "strange" or "different" and "lizard" or "reptile" literally to "different reptile". The second part of the name jimmadseni (gym-MAD-sehn-eye) honors the late Utah State Paleontologist James Madsen Jr. who excavated and studied tens of thousands of Allosaurus bones from the famous Cleveland-Lloyd Dinosaur Quarry in central Utah and contributed greatly to the knowledge of Allosaurus.

Size

Allosaurus jimmadseni was approximately 26 to 29 feet (8-9 meters) long.

Allosaurus jimmadseni weighed around 4000 lbs. (1.8 metric tonnes).

Relationships

Allosaurus jimmadseni belongs to a group of carnivorous dinosaurs called "allosauroids," the same group as the famous Allosaurus fragilis.

Other dinosaurs found in rocks containing Allosaurus jimmadseni include the carnivorous theropods Torvosaurus and Ceratosaurus; the long-necked sauropods Haplocanthosaurus and Supersaurus; and the plate-backed stegosaur Hesperosaurus.

Allosaurus jimmadseni is closely related to the State Fossil of Utah, Allosaurus fragilis.

Anatomy

Allosaurus jimmadseni was a two-legged carnivore, with long forelimbs and sharp, recurved claws that were likely used for grasping prey.

Like other allosauroid dinosaurs, Allosaurus jimmadseni had a large head full of 80 sharp teeth. It was also the most common carnivore in its ecosystem.

Age and geography

Allosaurus jimmadseni lived during the Kimmeridgian stage of the Late Jurassic period, which spanned from approximately 157 million to 152 million years ago.

Allosaurus jimmadseni lived in a semi-arid inland basin filled with floodplains, braided stream systems, lakes, and seasonal mudflats along the western interior of North America.

Allosaurus jimmadseni represents the earliest species of Allosaurus in the world.

Discovery

Allosaurus jimmadseni can be found in a geologic unit known as the Salt Wash Member of the Morrison Formation and its equivalents exposed in Colorado, Wyoming, and Utah.

The first specimen of Allosaurus jimmadseni was discovered in the National Park Service administered by Dinosaur National Monument in Uintah County, near Vernal, Utah.

Allosaurus jimmadseni was first discovered by George Engelmann of the University of Nebraska, Omaha on July 15, 1990 during a contracted paleontological inventory of the Morrison Formation of Dinosaur National Monument.

Another specimen of Allosaurus jimmadseni known as "Big Al," was found on land administered by the U.S. Department of the Interior's Bureau of Land Management in Wyoming.

Further specimens of Allosaurus jimmadseni have been subsequently recognized in the collections of various museums.

Allosaurus jimmadseni specimens are permanently housed in the collections of Dinosaur National Monument, Utah; the Museum of the Rockies, Bozeman, Montana; the Saurier Museum of Aathal, Switzerland; the South Dakota School of Mines, Rapid City, South Dakota; Brigham Young University's Museum of Paleontology, Provo, Utah; and the United States National Museum (Smithsonian) Washington D.C.

These discoveries are the result of a continuing collaboration between the Natural History Museum of Utah, the National Park Service, and the Bureau of Land Management.

Excavation

The first skeleton of Allosaurus jimmadseni was excavated during the summers of 1990 to 1994 by staff of the National Park Service's Dinosaur National Monument. The skeleton block was so heavy it required the use of explosives to remove surrounding rock and a helicopter to fly out the 2700 kg block. The head of the skeleton was missing

The first bones of Allosaurus jimmadseni discovered included toes and some tail vertebrae. Later excavation revealed most of an articulated skeleton missing the head and part of the tail.

The radioactive skull of the first specimen of Allosaurus jimmadseni, which had previously eluded discovery, was found in 1996 by Ramal Jones of the University of Utah using a radiation detector.

Preparation

It required seven years to fully prepare all of the bones of Allosaurus jimmadseni.

Much of the preparation was done by then Dinosaur National Monument employees Scott Madsen and Ann Elder, with some assistance from Dinosaur National Monument volunteers and students at Brigham Young University.

Other

The Natural History Museum of Utah houses the world's largest collection of Allosaurus fossils, which are frequently studied by researchers from around the world.

More than 270 National Park Service (NPS) areas preserve fossils even though only 16 of those were established wholly or in part for their fossils. Fossils in NPS areas can be found in the rocks or sediments of a park, in museum collections, and in cultural contexts (building stones, artifacts, historical legends, and documents).

The United States Bureau of Land Management manages more land--247 million acres--than any other federal agency, and manages paleontological resources using scientific principles and expertise.

The benefits of fetal surgery to repair spina bifida, a procedure pioneered at Vanderbilt University Medical Center (VUMC) in 1997, continue through school age, a National Institutes of Health (NIH) study reports today in the journal Pediatrics.

Children who underwent fetal surgery to repair a common birth defect of the spine are more likely to walk independently and have fewer follow-up surgeries compared to those who have the traditional corrective surgery after birth, according to the research funded by the National Institute of Child Health and Human Development (NICHD) of the NIH.

The longitudinal study of 161 children who had repairs for spina bifida, the most common birth defect in the central nervous system, was conducted at the three centers that participated in the original Management of Myelomeningocele Study (MOMS) - VUMC, Children's Hospital of Philadelphia and the University of California, San Francisco.

Myelomeningocele, the most serious form of spina bifida, is a complex congenital anomaly resulting from incomplete neural tube closure early in embryonic development. It occurs in about one in 1,500 births in the United States and results in a section of the spinal cord and spinal nerves being exposed through an opening in the back.

Before 1997, the repairs were performed after birth. The 1997 Vanderbilt surgery, performed by Noel Tulipan, MD, and Joseph Bruner, MD, introduced the ability to make the repairs in utero.

In a previous MOMS study, conducted from 2003-2010, the goal was to enroll 200 patients, but the National Institutes of Health ended the trial early after 183 surgeries, based on clear evidence that the prenatal surgery was effective.

The earlier trial found that fetal surgery reduced the need for a shunt by almost 30% and significantly improved the child's chances of being able to walk.

"This is a really unique cohort of patients," said John W. Brock III, MD, Senior Vice President of Pediatric Surgical Services at Monroe Carell Jr. Children's Hospital at Vanderbilt, Professor and Surgeon-in-Chief Emeritus and an author of the study.

"Vanderbilt has been a major player in this very important study. This study confirms that prenatal closure leads to improved mobility and independent functioning and a decreased need for ventricular peritoneal shunting. We have followed these children and mothers for 17 years and this is a continuation of that long-term follow-up. That's the uniqueness of this -- the mere fact that we have been able to do this for so long."

The current study, referred to as MOMS2, evaluated the long-term impacts of prenatal surgery compared with standard postnatal repair in children once they reached school age.

Of the 161 children taking part, 79 had been assigned to prenatal surgery and 82 to traditional surgery. Children in the prenatal surgery group walked independently more often than those in the traditional surgery group (93% vs. 80%). And those in the prenatal surgery group also had fewer shunt placements for hydrocephalus (fluid build-up) in the brain (49% vs. 85%) and fewer surgeries to replace shunts (47% vs. 70%). The prenatal group also scored higher on a measure of motor skills, but the two groups did not differ significantly in a test measuring communication ability, daily living skills and social interaction skills.

"Prenatal surgery for myelomeningocele carries benefits and risks, compared to traditional postnatal surgery," said Menachem Miodovnik, MD, of the NICHD Pregnancy and Perinatology Branch, in a press release. "This study provides important information for physicians with patients who are considering prenatal surgery."

Brock said that researchers plan to continue to follow the group of children. The specifics have not been decided.

Scientists have detected Marburg virus in fruit bats in Sierra Leone, marking the first time the deadly virus has been found in West Africa. Eleven Egyptian rousette fruit bats tested positive for active Marburg virus infection. Research teams caught the bats separately in three health districts.

The presence of Marburg virus, a close relative to Ebola virus that also causes hemorrhagic disease in people, was detected in advance of any reported cases of human illness in Sierra Leone. However, the virus's presence in bats means people who live nearby could be at risk for becoming infected. No outbreaks have been reported to date.

The findings, based on PCR, antibody and virus isolation data, were officially published today in the journal Nature Communications. Preliminary findings were announced earlier in December 2018 to ensure rapid notification to the citizens of Sierra Leone and the international health community.

The paper highlights the value of collaborating with government and key stakeholders across human, animal and environmental sectors to engage at-risk communities about the discovery, address health concerns and communicate risk-reduction strategies before recognized spillovers occur.

Marburg virus was detected by projects led by the Centers for Disease Control and Prevention, the USAID-funded PREDICT project led by the One Health Institute at the UC Davis School of Veterinary Medicine, Njala University, Sierra Leone and the University of Makeni, Sierra Leone.

"Finding Marburg virus in bats in Sierra Leone before any known cases in people is a huge success, as public health officials and doctors can now include Marburg virus among the possible causes when diagnosing hemorrhagic fever cases in the region," said Tracey Goldstein, co-principal investigator and pathogen detection lead for the PREDICT project from the UC Davis One Health Institute.

Angolan strains detected in bats for first time

To date, there have been 12 known outbreaks of Marburg virus with the most recent in Uganda in 2017. The largest and deadliest outbreak occurred in Angola in 2005 where 227 people died. Five of the new strains identified among the Marburg-positive bats in Sierra Leone were genetically similar to the strain that caused the outbreak in Angola. This is the first time scientists have detected these Angolan-like strains in bats.

The virus-positive bats were all Egyptian rousette bats, the known reservoir for Marburg virus, which primarily feed on fruit. Infected bats shed the virus in their saliva, urine and feces. Egyptian rousette bats are known to test-bite fruits, urinate and defecate where they eat, potentially contaminating fruit or other food sources consumed by other animals or people, particularly children. These bats sometimes serve as a food source for local populations as well. People may be exposed to Marburg virus through bat bites as they catch the bats.

Reducing risk of spillover through community outreach, risk-reduction training

Following the announcement of the preliminary findings by the government of Sierra Leone, the PREDICT team worked with government partners, universities and other key stakeholders to develop and implement evidence-based public health messaging across national, district, and local community levels in Sierra Leone.

Researchers and government officials met with community members to present their findings, answer questions about Marburg virus, and address how to reduce people's risk of exposure and live safely with bats. As an additional national-level public preparedness measure, Marburg virus disease has been included in testing regimens at national laboratories in Sierra Leone.

"PREDICT opened up the window to show there is more beyond Ebola, and demonstrated the need for partnership well before outbreak events unfold," said Amara Jambai, deputy minister of health for Sierra Leone.

Scientists emphasize that people should not attempt to kill or eradicate bats in response to the discovery. Bats play important ecological and agricultural roles. Fruit bats pollinate important crops, and insect-eating bats eat thousands of insects each night, including mosquitoes, which helps control pests that transmit disease and damage crops. Killing and coming into direct contact with bats can actually increase the risk of virus transmission, not halt it.

Finding viruses before they find us

The PREDICT team at UC Davis/University of Makeni and the team led by CDC/Njala University both began work in Sierra Leone in 2016 following the massive Ebola outbreak in West Africa. They each sought to discover the Ebola reservoir, the animal that helps maintain the virus in nature by spreading it without getting sick.

This Marburg discovery, the PREDICT team's discovery of the sixth ebolavirus--Bombali virus--in Angolan and little free-tailed bats in Sierra Leone, and its subsequent finding of Bombali virus in Angolan free-tailed bats in Guinea illustrate the strengths and mission of USAID's PREDICT project, which is to find viruses before they spill over into humans and become epidemics.

"Over a year ago, we worked with our Sierra Leone government colleagues to inform people across the country as fast as possible of this new health risk and remind people not to harm or come in contact with bats," said Brian Bird from the UC Davis One Health Institute and global lead for Sierra Leone and Multi-Country Ebola operations for PREDICT-USAID. "I'm very proud of that work and our teams now that this full report is available."

PHILADELPHIA -- (Jan. 24, 2020) -- In a study by The Wistar Institute and collaborators, a rare, African-specific variant of the TP53 gene called P47S causes iron accumulation in macrophages and other cell types and is associated with poorer response to bacterial infections, along with markers of iron overload in African Americans. Macrophage iron accumulation disrupts their function, resulting in more severe bacterial infections. The study, published online in Nature Communications, also showed that P47S macrophages exhibit improved response to the malaria toxin. This effect may confer protection against generalized inflammation associated with signs of acute malaria pathology.

The TP53 gene possesses numerous genetic variants, some of which are common in the population. Wistar scientists have previously shown that the P47S gene variant, which exists in populations of African descent, is associated with increased cancer risk in African Americans due to defects in an iron-mediated modality of cell death called ferroptosis. They have now discovered another notable effect of disrupted iron metabolism in cells that carry the P47S variant.

"We discovered that macrophages from mice carrying the P47S variant accumulate iron and this impairs their ability to mount an inflammatory response against bacterial infections, making them more susceptible to these diseases," said Farokh Dotiwala, M.B.B.S., Ph.D., assistant professor in the Vaccine & Immunotherapy Center and corresponding author of the study. "The flip side of diminished inflammation is that these mice have a more favorable response to malaria toxin hemozoin, that is responsible for most of the lethal symptoms in the acute phase of disease."

Along with Wistar's Maureen E. Murphy, Ph.D., Ira Brind Professor and leader of the Molecular & Cellular Oncogenesis Program at Wistar, and a co-senior author on the study, Dotiwala and his team found the frequency of the P47S variant to be significantly higher in African Americans from the HEIRS study (Hemochromatosis and Iron Overload Screening). Studying a mouse model carrying the human P47S variant of TP53, generated by the Murphy lab, researchers observed increased iron accumulation in macrophages.

Macrophages from P47S mice with higher iron content were less effective at controlling the growth of different bacterial species in vitro, which reflected faster disease progression and worse outcome.

To dissect the mechanisms of increased susceptibility of P47S mice to bacteria, Dotiwala and colleagues used proteomics to reveal changes in protein levels in macrophages. This approach showed modulation of several proteins involved in the immune response, particularly in metabolic pathways that are essential for macrophages to kill bacteria, such as the arginine pathway, and in ferroptosis. These changes reduced the ability of P47S macrophages to kill bacteria and were reversed by targeting three different affected pathways, thus highlighting future therapeutic potential.

Given the prevalence of the P47S gene variant in malaria-endemic regions of sub-Saharan Africa, the team asked whether this variant could confer a survival advantage to malaria infection. P47S mice injected with the malaria toxin hemozoin showed a weaker inflammatory response than mice carrying the common p53 gene variant. This may limit disease severity, which is a consequence of the massive generalized inflammatory response triggered by the toxin and mostly mediated by macrophages.

"While warranting further studies in humans, we believe that mechanistic knowledge obtained from studying the P47S variant provides a stepping stone in the field of personalized medicine to help address disparities arising from such polymorphisms," said Donna George, Ph.D., associate professor of genetics at the Perelman School of Medicine of the University of Pennsylvania and co-senior author on the study.

This study may also help understand the connection between the TP53 gene variant and iron overload disorders as well as the increased occurrence of certain bacterial infections and cancers found in African Americans.

A new study shows for the first time that the striking iridescent colours seen in some animals increase their chances of survival against predators by acting as a means of camouflage. Rather than reveal it seems these dynamically changing shades are used to conceal, according to the University of Bristol study published today [23 January] in Current Biology.

Until now, it was assumed that the iridescent colours seen in nature have two main purposes: they can help animals find mates, or act as a warning to predators that a prey item may be poisonous.

Researchers at Bristol's Camo Lab wanted to find out why this vivid metallic coloration has evolved in so many different species of animals by investigating its biological function. They chose to test this theory on the vividly coloured jewel beetle (Sternocera aequisignata) because both sexes of this species are iridescent which makes sexual signalling somewhat less likely as a function of the colour.

They tested the idea of iridescence-as-camouflage by placing iridescent and non-iridescent beetle models on leaves in the forest and noted their survival against attacks by wild birds. They found that the models with biological iridescence, survived best against birds, providing evidence that iridescence can increase prey survival and that these bright metallic colours could have evolved in beetles to confuse birds - their primary predator.

Dr Karin Kjernsmo, the study's lead author at the University of Bristol School of Biological Sciences, said: "Iridescent colours are most likely familiar to you from everyday objects such as soap bubbles and CDs, but this striking form of structural colour is also very common in nature. Iridescence has evolved independently in everything from jewel-like insects to shimmering birds and can even be spotted in your garden in insects such as Rose Chafers and Rosemary beetles.

"Although an iridescent insect might be easy to spot in a well-lit museum case, these spectacular colours may not shine as brightly in the dappled light of a natural environment, and so an iridescent beetle on a shiny leaf could be much more difficult to detect. If iridescence is to work as a form of protective coloration, it needs to work against birds, because birds are likely to be the most important predators of many iridescent insects."

However, the team wanted to investigate why the birds didn't attack the iridescent models and whether the increase in prey survival was due to camouflage or a warning colour effect. To test this, the researchers conducted a final experiment in which they asked human participants to search for the beetle models in the same environment. Warning colours should be easy to see, whereas if the beetles survived due to camouflage, the humans would not be able to detect them.

Dr Karin Kjernsmo, "I think that the biggest surprise to us was that when we carried out the same experiment with humans even they really struggled to spot the iridescent beetles. Both birds and humans really do have difficulty spotting iridescent objects in a natural, complex, forest environment.

"While the idea of 'iridescence as camouflage' itself is not new, our study is the first solid evidence for the idea that iridescence can work as highly-effective form of camouflage, and ultimately this could explain why iridescence has evolved in so many different species of animals."

Researchers from the group of Hans Clevers at the Hubrecht Institute (KNAW), in an international collaboration, have developed a method to grow snake venom gland cells as organoids. These lab-grown mini glands produce and secrete active toxins found in snake venom. Snake venom gland organoids can be grown from multiple species and maintained in the lab indefinitely. This new technology holds great promise to reduce the devastating impact and exploit the secrets of snake venom. The results of this research were published in the scientific journal Cell on the 23rd of January.

The dark and bright side of snakes and their venom have fascinated mankind for millennia. Snakebite kills more than 100.000 people (and disables an estimated 400,000 individuals) every year, while many more suffer from ophidiophobia, an abnormal fear of snakes. However, their toxins are also a rich source for new medicines and were already used for treatments in ancient Greece. Since then, many drugs have been inspired by snake venom, including drugs that lower blood pressure lowering drugs and prevent bleeding. Still, even in modern medicine, it has been challenging to fully exploit snake venom for drug development purposes and to protect people against its lethal potential. A few main obstacles are the cumbersome and dangerous process of milking snakes and the difficulty of studying and modifying venom factors in the glands of the snake.

Nine different snakes

Three PhD students working in the group of Hans Clevers at the Hubrecht Institute in Utrecht, the Netherlands, were inspired by their colleagues' successes of growing mini-versions of mammalian organs in the lab, called organoids. They wondered whether this would work for reptilians too, and whether they might be able to produce venom in the lab. They set up a collaboration with snake experts in Leiden, Liverpool and Amsterdam to collect venom glands from 9 different snakes and attempted to grow miniature versions of these glands in a dish.

Body temperature

After some tweaking of the conditions used to grow human organoids, the researchers developed a recipe that supports the growth of snake venom glands indefinitely. "The similarity between the growth conditions for human and snake tissues was staggering, with the main difference being the temperature", says Jens Puschhof (Hubrecht Institute). Since the body temperature of snakes is lower than that of humans, the venom gland organoids only grew at lower temperatures; 32ºC instead of 37ºC.

Active toxins

Through a high-resolution microscope, the researchers observed that the cells of the organoids are filled with dense structures that resemble the venom containing vesicles of the venom glands. Indeed, various analyses showed that the organoids produce the vast majority of venom components, or toxins, made by the snakes. For the first time, the researchers were able to study the toxin production of the individual cells in the venom gland. "We know from other secretory systems such as the pancreas and intestine that specialized cell types make subsets of hormones. Now we saw for the first time that this is also the case for the toxins produced by snake venom gland cells", explains Joep Beumer (Hubrecht Institute). In addition, the researchers found that changing the factors in the growth medium of the organoids could change the composition of the venom, giving them control over the kind of venom that is produced. In a collaborative effort, they showed that neurotoxins produced by the organoids are active and can block nerve firing in various cell systems, similar to the neurotoxins produced by the snakes themselves.

Anti-venoms and drugs

The findings of the researchers may have far-reaching consequences. Venom produced by the snake venom organoids could be used for antivenom production as well as for targeted development of new venom-based drugs. Further studies are in progress to develop these applications in the future. In addition, growing reptilian organoids for the first time suggests that tissues from other vertebrate animals (such as lizards, or fish) could also be grown this way. In fact, the researchers are currently setting up a large collection of venom gland organoids from 50 toxic reptilians, snakes and other venomous animals, together with reptilian expert Freek Vonk at Naturalis Biodiversity Center in the Netherlands, to study these different kinds of venom in the lab. Yorick Post (Hubrecht Institute): "It was amazing to see that what started with our curiosity about potential snake venom gland organoids transformed into a technology with many potential applications affecting human healthcare"

The sound produced by the vocal tract of a 3,000 year-old Egyptian mummy has been synthesized using CT scans, 3D printing and an electronic larynx. The findings are presented in a study published in Scientific Reports. The acoustic output is a single sound; it does not provide the basis for synthesizing running speech.

The precise dimensions of an individual's vocal tract produce a unique sound. If the dimensions of a vocal tract can be established, vocal sounds can be synthesized by using a 3D-printed vocal tract and an electronic larynx. For this to be feasible, the soft tissue of the vocal tract needs to be reasonably intact.

David Howard and colleagues used non-destructive CT to confirm that a significant part of the structure of the larynx and throat of the 3,000 year-old mummified body of the Egyptian priest Nesyamun remained intact as a result of the mummification process. This allowed the authors to measure the vocal tract shape from CT images. Based on these measurements, the authors created a 3D-printed vocal tract for Nesyamun and used it with an artificial larynx commonly used in speech synthesis. They were able to reproduce a single sound, falling between the vowels in the English words 'bed' and 'bad'.

The authors suggest that their proof-of-concept recreation of a vocal tract preserved over three millennia has implications for the way in which the past is presented to the public in the present; it may provide an opportunity to hear the vocal tract output of an individual that lived in ancient times.

Almost one-fifth of the whale sharks (Rhincodon typus) in Western Australia's Ningaloo Reef Marine Park show major scarring or fin amputations, with the number of injured animals increasing in recent years, new research reveals.

Distinctive scar patterns strongly suggest many of the injuries are caused by boat collisions, says whale shark scientist Emily Lester from the Australian Institute of Marine Science (AIMS).

To make the finding, Ms Lester, a PhD candidate at the University of Western Australia (UWA), and colleagues from AIMS and the Department of Biodiversity, Conservation and Attractions (DBCA), reviewed still and moving images of 913 whale sharks taken by Ningaloo tour boat operators between 2008 and 2013.

Of these, 146 or about 16% showed some form of serious injury.

"Some of the major scars were probably bite marks from predators, but most were the marks of blunt trauma, lacerations or amputations arising from encounters with ships, particularly propellers," Ms Lester said.

Whale shark diving is an important part of the Western Australian tourism industry, delivering an estimated at $12.5 million in economic activity for the Ningaloo Reef region.

However, because the species swim for thousands of kilometres beyond the marine park boundaries exactly where the injuries were sustained is unknown.

"Mitigating the impact of scarring from vessel collisions is challenging, particularly outside of our jurisdiction of State waters," said DBCA research scientist and co-author Dr Holly Raudino.

The results of the research show injuries recorded during 2012 and 2013 almost doubled compared to 2011.

"One possible explanation is that there is an increase in shipping activity throughout the whale sharks' range - inside Ningaloo and out - and collisions are becoming more frequent," said Ms Lester.

The data in the study cannot reveal the number of fatal ship collisions, because whale sharks are 'negatively buoyant', meaning that when they die they sink to the ocean floor.

"A collision between a large ocean-going vessel and a whale shark wouldn't be felt by the ship, as a result, it's likely that we're underestimating the number of mortalities from ship strike, since our study could only document sharks that survived their injuries," Ms Lester said.

Dr Raudino, whose expertise is marine fauna, added that the first step in reducing these interactions would be by "identifying hotspots of where these collisions are occurring through spatial modelling".

The research is published in the Marine Ecology Progress Series.

Despite regulatory frameworks designed to prevent environmental damage, pesticide use is still linked to declines in insects, birds and aquatic species, an outcome that raises questions about the efficacy of current regulatory procedures. In a Policy Forum, Christopher Topping and colleagues argue that this discordance between pesticide policy and their observed impacts stems from aging Environmental Risk Assessment (ERA) regulations, which have fallen out of line with environmental policy and with the science behind our current ecological reality. In both the European Union and the United States, basic ERA guidelines are decades old and based on assumptions that misrepresent the dynamic ecological systems in modern agricultural landscapes. For example, ERA typically does not account for the fact that climate change, habitat loss and large-scale landscape homogenization can exacerbate the adverse impacts of pesticides. According to the authors, a radical overhaul of ERA is required in order to implement a regulatory framework that delivers adequate environmental protection. Topping et al. propose a more holistic, integrated systems-based approach to pesticide regulation, which would be better able to align multiple agricultural practices with dynamic agroecological factors in pesticide regulation. While this radical change would require challenging changes to administrative structures and a reevaluation of current protections regulations, the fundamental science, technology and data required to support such a system are already available, the authors say.

Through modern chemistry, we live better. However, as researchers continue to recognize the environmental and health risks associated with the mass production, use and disposal of complex synthetic molecules, a need for safer and more sustainable chemicals has become clear. In this special issue of Science, "Chemistry for Tomorrow's Earth," four Reviews, a Perspective and a related feature from Science's news department chart a path towards a cleaner and greener future for the chemical industry on which we all rely, while reckoning with the hazardous legacy left in its wake. To introduce the issue, Science editors Michael Funk and Caroline Ash ask: "How can we continue to develop molecules that address the challenges we face today while ensuring we understand the effects of the complex and ubiquitous chemicals we produce on our health and the environment? ... Our health, and that of ecosystems around the world, depend on our commitment to gathering this information and taking action accordingly."

Nearly 140,000 different industrial chemicals are currently used worldwide, and their complexity presents a challenge to developing the circular economy needed to make the chemical industry sustainable - one aimed at eliminating waste by circulating and recycling chemical products. In a Perspective, Klaus Kümmerer and colleagues argue that achieving a circular economy for chemicals requires a rethinking of chemistry, involving efforts like keeping molecular complexity to a minimum when designing new compounds and designing products with recycling in mind. In a Review, Julie Beth Zimmerman and colleagues argue that the important inherent properties of new molecules need to be considered at the early stages of chemical design. To avoid the pitfalls of the past, Zimmerman et al. suggest that chemical performance should not only be evaluated by functionality, but also by if compounds are non-depleting, non-toxic and non-persistent. In another Review, Andrew Johnson and colleagues emphasize that the sheer diversity of chemical compounds used today puts the ability to assess their total risks beyond our reach. However, our past experience with environmental chemicals may be used in modeling hazards and gauging relative risk, they say. In a third Review, Beate Escher and colleagues discuss the detection and characterization of chemical mixtures in indoor and outdoor environments. Currently, tracking groups of chemicals and the toxicological effects of the products they inadvertently create when combined is a great challenge. To address this, Escher et al. propose a new approach, which combines chemical analysis with bioassays to identify potentially harmful mixtures in the environment. A final Review, by Roel Vermeulen and colleagues, discusses the "exposome" concept conceived in 2005 as a way of understanding the non-genetic factors associated with disease and health related to chemical exposures. The authors review several recently developed technologies for measuring multiple chemical exposures in high-throughput analyses, similar to genome-wide association studies.

Lastly, in a news Feature, Science contributing correspondent Warren Cornwall reports on how one chemical company is teaming up with some unlikely allies. Many food and beverage cans are lined with BPA, a chemical that has long been the focus of health concerns. Chemical company Sherwin-Williams has taken an unusual approach to finding an alternative: joining up with some of BPA's fiercest critics.