Culture

Finnish research team maps neural activity in response to watching horror movies. A study conducted by the University of Turku shows the top horror movies of the past 100 years, and how they manipulate brain activity.

Humans are fascinated by what scares us, be it sky-diving, roller-coasters, or true-crime documentaries - provided these threats are kept at a safe distance. Horror movies are no different.

Whilst all movies have our heroes face some kind of threat to their safety or happiness, horror movies up the ante by having some kind of superhuman or supernatural threat that cannot be reasoned with or fought easily.

The research team at the University of Turku, Finland, studied why we are drawn to such things as entertainment? The researchers first established the 100 best and scariest horror movies of the past century (Table 1), and how they made people feel.

Unseen Threats Are Most Scary

Firstly, 72% of people report watching at last one horror movie every 6 months, and the reasons for doing so, besides the feelings of fear and anxiety, was primarily that of excitement. Watching horror movies was also an excuse to socialise, with many people preferring to watch horror movies with others than on their own.

People found horror that was psychological in nature and based on real events the scariest, and were far more scared by things that were unseen or implied rather than what they could actually see.

- This latter distinction reflects two types of fear that people experience. The creeping foreboding dread that occurs when one feels that something isn't quite right, and the instinctive response we have to the sudden appearance of a monster that make us jump out of our skin, says principal investigator, Professor Lauri Nummenmaa from Turku PET Centre.

MRI Reveals How Brain Reacts to Different Forms of Fear

Researchers wanted to know how the brain copes with fear in response to this complicated and ever changing environment. The group had people watch a horror movie whilst measuring neural activity in a magnetic resonance imaging scanner.

During those times when anxiety is slowly increasing, regions of the brain involved in visual and auditory perception become more active, as the need to attend for cues of threat in the environment become more important. After a sudden shock, brain activity is more evident in regions involved in emotion processing, threat evaluation, and decision making, enabling a rapid response.

However, these regions are in continuous talk-back with sensory regions throughout the movie, as if the sensory regions were preparing response networks as a scary event was becoming increasingly likely.

-Therefore, our brains are continuously anticipating and preparing us for action in response to threat, and horror movies exploit this expertly to enhance our excitement, explains Researcher Matthew Hudson.

Like animals and humans, plants possess a kind of immune system. It can e.g. recognize pathogenic fungi by the chitin in their cell walls, triggering disease resistance. Some fungi hide from the immune system by modifying some of the chitin building blocks, converting chitin into chitosan. Researchers of the University of Münster now found that plants can react to a certain pattern in this chitosan, stimulating their immune system. They are already developing a chitosan-based plant immune-stimulant in order to reduce the use of chemical pesticides in agriculture. Their results are published in JACS (Journal of the American Chemical Society).

Background

Chitosans, so-called polysaccharides, are probably the most versatile and promising functional biopolymers. Chitosans can make plants resistant to diseases, promote their growth, and protect them from heat or drought stress. Under chitosan dressings, even large wounds can heal without scars, chitosan nanoparticles can transport drugs across the blood/brain barrier, and chitosans can replace antibiotics in animal fattening as antimicrobial and immunostimulating feed additives. But of course, chitosans are not miracle cures either. "There are many different chitosans and for each individual application, exactly the right one must be found to make it work. Until now, we knew far too little about their effects and how they can be used effectively. With our research, we have now come a step closer to this understanding", explains Prof Bruno Moerschbacher from the Institute for Biology and Biotechnologies of Plants at Münster University.

Chitosans consist of chains of different lengths of a simple sugar called glucosamine. Some of these sugar molecules carry an acetic acid molecule, others do not. Chitosans therefore differ in three factors: the chain length and the number and distribution of acetic acid residues along the sugar chain. For about twenty years, chemists have been able to produce chitosans of different chain lengths and with different amounts of acetic acid residues, and biologists have then investigated their biological activities. Thus, an understanding slowly developed of how these two factors influence the antimicrobial or plant-strengthening effect of chitosans. Such well-characterized chitosans, now called second-generation chitosans, are currently used as the basis for new chitosan-based products such as the plant biostimulant "Kitostim" which was developed based on the research results of the Münster team. It promotes growth and development of plants, and it strengthens them against disease and heat stress.

Bruno Moerschbacher suspected early on that the third structural factor, the distribution of acetic acid residues along the sugar chain, also plays a decisive role in determining biological activities. However, this hypothesis could not be tested for a long time because the acetic acid residues are randomly distributed in all chemically produced chitosans. As biochemists and biotechnologists, the members of his team have therefore used enzymes for the production of chitosans, i.e. the natural 'tools' involved in the biosynthesis of chitosan in chitosan-containing fungi. With their help, they have now succeeded in producing short chitosan chains, so-called oligomers, with a defined arrangement of acetic acid molecules, and tested their bioactivity.

For this test, the researchers used rice cells that they treated with chitosan oligomers to stimulate their immune system. When they used chitosan oligomers consisting of four sugar units (so-called tetramers) carrying only a single acetic acid residue, they found that the tetramer with the acetic acid residue at the first ('left-most') sugar unit (the so-called non-reducing end) had a strong immunostimulating effect, while the other three tetramers were less active or inactive. Thus, very clear differences in bioactivity were found between chitosans with the same chain length (four) and the same number of acetic acid residues (one) when they differed in the position of the acetic acid residue. The researchers led by Bruno Moerschbacher are currently testing the use of this tetramer as a kind of vaccine that stimulates the plants' natural immune system.

Outlook

Such a clear dependence of the bioactivity of a complex sugar on its molecular structure has almost never been observed before. The first and to date only example was human heparin, whose anticoagulant effect is based on a certain distribution of sulphuric acid residues along the sugar chain. It is now known that heparin achieves this effect by binding a coagulation factor to this specific binding site, thus inactivating it. And on the basis of this knowledge, it has been possible to develop anticoagulants with precisely dosed effects and without side effects, which are a blessing for e.g. dialysis patients. "It is now our hope that the precisely defined chitosans can be used in a similar way to enable, for example, scar-free wound healing under chitosan dressings," said Bruno Moerschbacher, whose research group is already collaborating with dermatologists and other biomedical experts.

Particularly in the case of accelerated drug approvals and drugs for rare diseases (orphan drugs), the evidence available at the time of market access is often insufficient for the early benefit assessment of drugs. Often, the studies are too short or no data on patient-relevant outcomes were collected. Comparisons with the German standard of care are also often lacking. In order to close such evidence gaps, in future, routine practice data are also to be included in early benefit assessments of drugs.

But how must the data be collected and processed so that they can be used by the Federal Joint Committee (G-BA) for benefit assessments in Germany? In order to answer this question, the G-BA commissioned the Institute for Quality and Efficiency in Health Care (IQWiG) to develop scientific concepts for the generation of routine practice data and their analysis for benefit assessments of drugs - especially with regard to the option of quantifying the added benefit of a new drug. According to the "Gesetz für mehr Sicherheit in der Arzneimittelversorgung" (GSAV, Law for More Safety in the Supply of Medicines), the G-BA may in future commission the collection of routine practice data on selected drugs to support the quantification of added benefit.

Summarizing the most important result of the IQWiG analysis, Jürgen Windeler, IQWiG's Director, notes: "Extensive analyses of the methodological literature and intensive discussions with registry operators and external statisticians have led us to the conclusion that, in the case of high-quality patient registries, it is possible to base studies on these registries and use the routine practice data collected for extended benefit assessments of drugs."

Such registry studies can be conducted either with or without randomization, but the high quality of the data is the decisive factor in both cases.

In order to support the individual registries in particular and the registry landscape in Germany in general in the collection of routine practice data, on the basis of current national and international recommendations, IQWiG compiled criteria for data quality and for ensuring data quality for routine practice data collections for benefit assessments of drugs, condensed them to the essentials, and organized them in a clear and concise manner. In addition, the rapid report provides registry operators, sponsors of registry studies as well as health policy decision-makers with specific recommendations for action on how the collection of routine practice data in registries can be made usable for benefit assessments of drugs.

Focus on collection of routine practice data in registries

Routine practice data are data collected within the context of usual health care in patient populations that can receive the drug under assessment in the approved therapeutic indication. The data can be collected in studies with or without randomization.

In their rapid report, the IQWiG authors describe that the use of routine practice data for benefit assessments of drugs mandatorily requires a comparison between the new drug and the comparator therapy specified by the G-BA, which makes it necessary to conduct comparative studies. In general, four data collection tools are available for comparative studies: study-specific data collection as well as data collection from registries, electronic patient records, and claims data of health insurance funds.

The IQWiG authors are convinced that the collection and processing of routine practice data from electronic patient records and claims data from health insurance funds is currently not possible with regard to benefit assessments of drugs and will not be possible in the near future. This is mainly because the data quality in these sources is insufficient and important data are not collected. These problems cannot be solved in the short or medium term. In contrast, the assessment of disease-related patient registries yielded positive results.

Data quality of registries has improved

As the IQWiG authors note, of the data collection tools not primarily geared towards comparative studies, registries are most likely to offer the option of adapting the data collection requirements for these studies. This concerns both the specification of the necessary data and the data quality.

The authors also note that the question as to whether existing patient registries are currently suitable for the collection of routine practice data according to §35a Social Code Book (SGB V) cannot be answered in a general way. This depends on the respective registry and, above all, on the specific research questions posed. In the discussions with selected registry operators, however, it also became apparent that from a technical and organizational point of view, the registries are generally prepared to implement any necessary extensions of the data set.

Thomas Kaiser, Head of IQWiG's Drug Assessment Department explains: "In recent years, the objectives and scope of documentation of registries have been extended. In particular, the increasing documentation of clinical information in registries that can be used to describe patient populations, interventions and outcomes for benefit assessments is an important step forward. For certain research questions, data on patient-reported outcomes should also be included in registries. This is already the case in some registries."

Benefit assessments always require fair comparisons

As emphasized by the IQWiG authors, if routine practice data are to be used in benefit assessments, it must be taken into account that the basis of any conclusion on the effects of interventions is a comparison. This is because only on the basis of a comparison is it possible to distinguish between "after intervention A" and "due to intervention A"; this distinction is necessary for a causal conclusion. A comparison is only meaningful if the starting conditions are fair (similarity of the groups in terms of prognostic factors). Ideally, this is achieved through randomization, i.e. the random allocation of study participants to the two study arms.

When studies are conducted without randomization, the adjustment of interfering factors (confounders) is an essential part of the assessment. For this purpose, the relevant confounders - such as the severity of a concomitant disease or a genetic mutation - must be determined and documented in the data collection. The completeness and accuracy of the data on confounders is just as important as that of the other data. Depending on the research question and the data already available, it may therefore be less resource-intensive to conduct a study with randomization.

As the IQWiG authors note, in order to be able to use routine practice comparative studies for benefit assessments, it should already be ensured in the study planning phase that the study process and the data collected are of the necessary quality to produce interpretable results.

They therefore compiled a clear list of criteria to ensure that only data of sufficient quality are used. This list is divided into four categories: mandatory criteria for ensuring data quality; general criteria that are always relevant for registry studies used in benefit assessments of drugs; general criteria that, depending on the research question, are relevant for registry studies used in benefit assessments of drugs; and criteria whose degree of fulfilment is to be assessed in relation to the research question.

Thomas Kaiser notes: "In the context of the suitability testing of a specific registry, this list should be used to evaluate for the respective research question whether all necessary data have been collected or whether possible deficits can be corrected with reasonable effort in a registry-based study."

Without randomization, no more than a hint of an effect is conceivable

The smaller the expected differences in treatment effects in a comparison, the more important is a fair comparison in terms of the similarity of the groups in terms of prognostic factors described above. From this, the IQWiG authors conclude that from comparative studies without randomization, a conclusion drawn from the observed effects with regard to the benefit or harm of an intervention is only meaningful if a certain effect size is exceeded. Otherwise, it cannot be excluded that the observed effect was not caused by the intervention, but by confounders. Since without randomization it cannot be excluded, even in a good study, that unknown confounders may influence the results, it is therefore generally not possible to derive more than a hint of an effect from comparative studies without randomization.

According to IQWiG's analysis, whether it is possible to consider retrospective study designs depends on whether the available data sources contain the necessary data in the required quality. Thus, comparisons of patient populations receiving a new drug with patient populations comprising historical controls only appear realistic if the same data source is used for both (e.g. a disease-specific clinical registry).

Registry-based randomized trials as an option

In general, comparative studies with randomization always have a higher informative value than those without randomization. They remain the gold standard because quantification of the added benefit is more reliable. The IQWiG authors emphasize that, particularly after drug approval, routine practice comparative trials with randomization can - depending on the existing research question - also be conducted with a limited collection of data in "large simple trials". Conducting studies in registries has an additional potential to accelerate the studies and make them less complex and resource-intensive (registry-based comparative studies with randomization).

Jürgen Windeler, IQWiG's Director, concludes: "The generation of routine practice data and their analysis is potentially feasible in the near future - but for the time being, in addition to study-specific data collection, only via data collection from registries. We have documented which data must be available in the registries and in what quality. The registry operators were very open-minded in their discussions with us, so I expect that the first data from high-quality registries will soon be available for use in benefit assessments of drugs." In this context, Windeler also calls on politicians to act: "The conditions for high quality registries could be better. This concerns both funding and the fact that there are different requirements for data protection in different German federal states."

Fentanyl use by people who use drugs has doubled since 2015, and two-thirds of people are aware they've taken it, finds new research out of British Columbia, the Canadian province that has experienced the highest number of illicit drug toxicity deaths as a result of the opioid crisis.

The findings point to the importance of taking comprehensive measures to reduce the risk for people who take the toxic opioid knowingly or unknowingly. The study, by the BC Centre for Disease Control (BCCDC) and University of British Columbia, is based on 2018 survey data collected from people who visit harm reduction sites for supplies like new syringes and needles or safer smoking supplies. The study, published this week in the International Journal of Drug Policy, provides valuable insights into fentanyl use that will inform efforts to reduce overdoses and deaths in B.C. and beyond.

"This research shows the majority of people who use fentanyl know they're doing so," says Dr. Jane Buxton, BCCDC epidemiologist, harm reduction lead and professor in the UBC School of Population and Public Health. "Making people who use drugs aware of the presence of fentanyl in the drug supply isn't enough; we need harm reduction services, substance use treatment, overdose prevention resources, and pharmaceutical alternatives to the toxic drug supply to reduce the devastating impact of fentanyl and its analogues on our communities."

Fentanyl is a synthetic opioid 50 to 100 times more toxic than morphine According to preliminary data from the BC Coroner's Service, fentanyl or its analogues such as carfentanil were found in 85 per cent of fatal overdose cases in 2019.

When fentanyl first appeared in the drug supply, many people took fentanyl unknowingly in the drugs they sought like heroin, counterfeit opioid tablets or other substances. At the time, B.C. saw a huge spike in deaths from the contaminated drug supply and instituted measures to prevent deaths including distribution of kits containing the overdose reversing drug naloxone, increased access to treatments for opioid use disorder susbtitiuation treatment, and expansion of overdose prevention services and supervised consumption sites. Scientists and health care workers wanted to know whether people were still unaware they were taking fentanyl, so they repeated a study done in 2015, shortly after fentanyl entered the drug supply.

The study drew on data collected from 303 participants recruited from 27 harm reduction sites across B.C. The participants completed a brief survey on their drug use and provided a urine sample that researchers tested for fentanyl and other substances.

Sixty per cent of participants in 2018 had fentanyl detected in their urine, of these people, 64 per cent knew they had taken fentanyl. The study done in 2015 found 29 per cent of participants tested positive for fentanyl, with only 27 per cent aware that they'd used it.

Researchers do not fully understand the factors that contribute to people knowingly taking fentanyl, but the reasons are varied. Some people may use fentanyl because they are aware it is present in most of the illicit supply of opioids and therefore have no other choice, while some may prefer the experience of taking fentanyl regardless of other options.

"This research lays groundwork that will help us learn more about why fentanyl use is increasing," says Mohammad Karamouzian, PhD student at UBC's School of Population and Public Health and a lead author of the study. "These findings will also contribute to more effective messaging campaigns and harm reduction strategies to help reduce preventable deaths and support the health of people who use substances, their families, and their communities."

Quick facts

Other key findings from the study include:

Recent fentanyl use was more common in people living in urban settings.

People who used fentanyl were more likely to have also recently used heroin/morphine or crystal meth.

Self-reported cannabis use was associated with reduced fentanyl use.

The data for this study were collected at harm reduction sites that provide a range of services to people who use drugs including, but not limited to: condom distribution, needle and syringe distribution and take-home naloxone kits. There are approximately 375 of these facilities across B.C.

A study led by BCCDC in 2019 showed the rapid expansion of harm reduction services (e.g., take home naloxone, opioid agonist therapy and overdose prevention sites) in response to B.C.'s overdose crisis averted more than 3,000 overdose deaths during a 20-month period in 2016-2017.

Arlington, Va. - New research funded by the Frozen Food Foundation evaluates current environmental monitoring practices being implemented across the frozen food industry to prevent and control Listeria monocytogenes (Lm). The findings were published in the January 24, 2020, Journal of Food Protection®.

The University of Georgia (UGA) study used an anonymous survey tool to understand existing environmental monitoring programs across a variety of frozen food manufacturing facilities. Information from more than 45 frozen food facilities was collected and, while monitoring practices were varied across the industry, the data indicated that facilities were predominantly testing for Listeria spp. in the environment (i.e. walls, floors and drains).

"This study is part of the frozen food industry's commitment to better understand Listeria in frozen food facilities by reviewing current practices," said Frozen Food Foundation Executive Vice President Dr. Donna Garren. "This research helps implement the frozen food industry's science-based environmental monitoring programs to identify and reduce the risk of Lm that are available at AFFIFoodSafety.org."

The lead researcher, Dr. Mark Harrison stated that, "There is a need for facilities to review their sampling strategy including the frequency and timing of sampling." He further added, "Facilities should focus on looking for Lm at times and in places where they are most likely to find the pathogen for a realistic assessment."

"Lm is a challenge because of its ubiquity and ability to survive freezing," said Dr. Garren. "UGA's research will help the frozen food industry identify appropriate sampling locations, timing and frequency to address the potential risk of this pathogen."

This research will continue throughout 2020 as UGA analyzes quantitative environmental monitoring data aggregated from frozen food companies to serve as an important baseline for future assessments.

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."