Culture

Reston, VA--Insights into how the heart recovers after myocardial infarction (heart attack) can be obtained with a new radiotracer that targets fibroblast activity prior to it causing permanent damage. According to research published in the December issue of The Journal of Nuclear Medicine, 68Ga-FAPI-04 positron emission tomography (PET) can effectively image fibroblast activation after myocardial infarction, identifying a time window during which cardiac fibrosis can be prevented and the disease course altered.

After a heart attack, fibroblasts play an important role in tissue replacement, preserving the structural integrity of the heart. However, excessive fibrosis can lead to increased left ventricle stiffness and decreased cardiac contraction. As heart failure remains a major source of late morbidity and mortality after a heart attack, study authors sought to evaluate the feasibility of imaging activated fibroblasts after myocardial infarction using a novel 68Ga-labeled fibroblast activation protein (FAP) inhibitor.

"We know that the temporospatial presence of activated fibroblasts in the injured myocardium predicts the quality of cardiac remodeling after a heart attack," noted Zohreh Varasteh, PhD, research fellow at Klinikum rechts der Isar der TUM in Munich, Germany. "Therefore, imaging of activated fibroblasts using 68Ga-FAPI-04 PET may have significant diagnostic and prognostic value, which could aid in the clinical management of patients after myocardial infarction."

The preclinical study included 20 rats subjected to myocardial infarction by permanent ligation of the left anterior descending coronary artery, as well as four sham-operate rats that underwent the same procedure except the ligation. In vivo imaging with 68Ga-FAPI-04 PET was performed at one, three, six, 14, 23 and 30 days after the myocardial infarction and with 18F-FDG three days after myocardial infarction. Dynamic 68Ga-FAPI-04 PET and blocking studies were performed on the myocardial infarction rats on day seven. Ex vivo imaging, autoradiography, histologic studies and immunofluorescence staining were also conducted to validate results of in vivo imaging.

Researchers found that uptake of 68Ga-FAPI-04 PET peaked six days after ligation and decreased rapidly to the background level by two weeks after infarction. Uptake accumulated mainly at the border zone of the infarcted myocardium, with high contrast and minimal uptake in normal myocardium. Minimal uptake was noted in rats that received a blocking dose of non-labeled FAPI-04. The exact location of the 68Ga-FAPI-04 uptake was confirmed by ex vivo imaging, as well as autoradiography and histologic findings.

"While preclinical development of potential anti-fibrotic approaches is far advanced, there has been little clinical validation due to the lack of sensitive and specific imaging technologies for assessing cardiac fibrosis progression or regression. In this regard, 68Ga-FAPI-04 PET has emerged as an important tool for the detection of fibrotic processes in the efforts to improve heart failure therapy," Varasteh said.

Varasteh continued, "In the future, these advances in imaging may also be applied to other conditions associated with the activation of fibroblasts, such as hypertension, ischemic, dilated and hypertrophic cardiomyopathies, cancer therapy-related cardiotoxicity, liver cirrhosis and pulmonary fibrosis."

Researchers from the University of Maryland School of Medicine and their colleagues have identified the structure of the most lethal toxin produced by certain strains of Clostridium difficile bacteria, a potentially deadly infection associated with the use of antibiotics. The finding, published today in the Proceedings of the National Academy of Sciences journal, used cryo electron microscopy, X-ray crystallography and other biophysical methods to identify the microscopic structures of the bacteria. The researchers mapped out the delivery and binding components of the toxin, which could pave the way for new drugs to neutralize it.

"We identified two structures that help explain the molecular underpinnings of C. difficile toxicity," said study co-author David Weber, PhD, a Professor of Biochemistry and Molecular Biology and Director of the Center for Biomolecular Therapeutics at UMSOM. "These structures will be important for targeting this human pathogen using structure-based therapeutic design methods."

Certain C. difficile infections are notoriously difficult to treat and often arise from antibiotic therapy given to fight other infections, which wipes out the beneficial bacteria that normally keep C. difficile bacteria in check. More than 500,000 cases occur annually in the United States, according to the Centers for Disease Control and Prevention, resulting in an estimated 15,000 deaths, usually from strains that are resistant to antibiotic treatment.

There is currently no drug approved by the Food and Drug Administration that targets the C. difficile toxin (CDT) or "binary toxin".

The work was done in conjunction with researchers at the City University of New York, City College of New York, the National Institute of Standards and Merck & Co.

With the mapping of the structures of one of the binary toxins, called CDTb, the researchers next aim to answer important new questions regarding the molecular mechanism of the C. difficile toxin, which can also benefit drug discovery. For example, they will investigate how the active binary toxin complex assembles and dissociates, how it binds to a healthy cell in a patient's gastrointestinal tract and how it enters the cell.

Nations across the world are following a United Nations blueprint to build a more sustainable future - but a new study shows that blueprint leads less to a castle in the sky, and more to a house that needs constant remodeling.

Sustainability scientists have developed systematic and comprehensive assessment methods and performed the first assessment of a country's progress in achieving all 17 UN Sustainable Development Goals (SDGs) not just as a nation, but also at the regional levels, and not just as a snapshot - but over time.

In "Assessing progress towards sustainable development over space and time" in this week's Nature, scientists from Michigan State University (MSU) and in China show that indeed all sustainability, like politics, is local.

Even as a country can overall claim movement toward a sustainable future, areas within the country reflect the gains and losses in the struggle with poverty, inequality, climate, environmental degradation and for prosperity, and peace and justice. Most striking, the study found, is the disparities between developed regions and ones that are developing.

"We have learned that sustainability's progress is dynamic and that sometimes gains in one important area can come at costs to another area, tradeoffs that can be difficult to understand but can ultimately hobble progress," said Jianguo "Jack" Liu, MSU Rachel Carson Chair in Sustainability and senior author. "Whether it's protecting precious natural resources, making positive economic change or reducing inequality - it isn't a static score. We must carefully take a holistic view to be sure progress in one area isn't compromised by setbacks in other areas."

The group assessed China with methods that can be applied to other countries. China's vast size and sweeping socioeconomic changes at national and provincial levels showed how progress in sustainability can shift. Between 2000 and 2015, China has improved its aggregated SDG score.

At the provincial level, however, there is a disparity between the country's developed and developing regions. East China - which is home to the country's economic boom -- had a higher SDG Index score than the more rural west China in the 2000s. In 2015, south China had a higher SDG Index score than the industrialized and agricultural-intensive north China.

Zhenci Xu, a recent PhD graduate from MSU's Center for Systems Integration and Sustainability (MSU-CSIS) who led the study, notes that countries are tasked with urgent goal of achieving sustainability even as populations grow, economies develop unevenly, natural resources like water and energy become scarce, land degrades, and income and gender inequities intensify.

Developed provinces had higher (and thus better) SDG Index scores than developing provinces throughout the study period of 2000-2015. But the average SDG Index scores in developing provinces were increasing faster compared to developed provinces.

"China's eastern region began developing during the reform and opening-up policy in the late 70s to spur economic development along the coasts, which was accompanied by better social services," Xu said. "In 1999, China started to address the rural western parts which had lagged in progress. That saw improvements both in infrastructure and ecological conservation, which seems to have boosted their sustainable development. The eastern parts have begun to struggle with the consequences of rapid economic growth - such as pollution and inequities."

The authors note that overall sustainability is advancing thanks to better education, healthcare and environmental conservation policies. The study points out that even amidst progress, it is important to scrutinize what is happening at regional levels to know where to direct resources and attention.

Heart disease remains the largest killer in Australia and around the world. A new study has shown that a protein therapy- recombinant human platelet-derived growth factor-AB (rhPDGF-AB) - could improve outcomes following heart attack.

After a heart attack, scar tissue forms and this negatively affects heart function. Now, researchers from The Westmead Institute for Medical Research (WIMR) and the University of Sydney found that, infusing rhPDGF into subjects that have had heart attacks improves the quality of the scar, leads to the formation of new blood vessels in the heart, and reduced rates of dangerous heart arrhythmia (irregularities of heart rhythm that can cause sudden death).

This study was in a pre-clinical large animal model.

The discovery publishes today in the leading journal Science Translational Medicine.

Corresponding author who led the research team, Associate Professor James Chong, said: "This is an entirely new approach with no current treatments able to change scar in this way.

"By improving cardiac function and scar formation following heart attack, treatment with rhPDGF-AB led to an overall increase in survival rate in our study.

"While the treatment did not affect overall scar size, importantly we found that rhPDGF-AB led to increased scar collagen fibre alignment and strength. This improved heart function after the heart attack.

"Our collaborator Professor Richard Harvey,from the Victor Chang Cardiac Research Institute, had previously shown that the protein can improve heart function in mouse models following heart attack.

"This project has been developed over more than 10 years and we now have compelling data in two species for the effectiveness of this treatment.

Following heart attack, the heart muscle is damaged, causing thick scar tissue to form. This can limit the heart's ability to function efficiently, and can increase the risk of heart failure, and sudden cardiac death.

Current treatments aim to restore blood and the oxygen supply to the heart as quickly as possible to reduce scarring. While this improves clinical outcomes, up to a quarter of patients experiencing their first heart attack will develop heart failure within one year.

Associate Professor Chong said: "While we have treatment protocols in place, it's clear that there is an urgent, unmet need for additional treatments to improve patient outcomes particularly after large heart attacks.

"Heart disease is the leading cause of death in Australia. It is thought that more than 400,000 Australians have had a heart attack at some stage in their lives and that there is roughly one heart attack every 10 minutes. Through our research, we have the opportunity to change the negative impact of these statistics.

"Some further animal studies are required to clarify safety and dosing. Then we can start looking towards clinical trials in humans very soon. rhPDGF-AB is clearly a promising therapeutic option, and could potentially be used alongside existing treatments to improve heart attack patient outcomes and survival rates.

"We now hope to further investigate the treatment, including whether it could be used in other organ systems impacted by scar tissue, such as the kidneys."

More than half of Earth's rivers freeze over every year. These frozen rivers support important transportation networks for communities and industries located at high latitudes. Ice cover also regulates the amount of greenhouse gasses released from rivers into Earth's atmosphere.

A new study from researchers in the University of North Carolina at Chapel Hill Department of Geological Sciences found that annual river ice cover will decline by about six days for every one degree Celsius increase in global temperatures. This decline will have economic and environmental consequences. The study, "The past and future of global river ice," was published Jan. 1 in the journal Nature. It is the first study to look at the future of river ice on a global scale.

"We used more than 400,000 satellite images taken over 34 years to measure which rivers seasonally freeze over worldwide, which is about 56% of all large rivers," said Xiao Yang, a postdoctoral scholar in the UNC-Chapel Hill geological sciences department and lead author on the paper. "We detected widespread declines in monthly river ice coverage. And the predicted trend of future ice loss is likely to lead to economic challenges for people and industries along these rivers, and shifting seasonal patterns in greenhouse gas emissions from the ice-affected rivers."

The team also looked at changes to river ice cover in the past and modeled predicted changes for the future. Comparing river ice cover from 2008-2018 and 1984-1994, the team found a monthly global decline ranging from .3 to 4.3 percentage points. The greatest declines were found in the Tibetan Plateau, eastern Europe and Alaska.

"The observed decline in river ice is likely to continue with predicted global warming," the study explains.

For the future, the team compared expected river ice cover through 2009-2029 and 2080-2100. Findings showed monthly declines in the Northern Hemisphere ranging from 9-15% in the winter months and 12-68% during the spring and fall. The Rocky Mountains, northeastern United States, eastern Europe and Tibetan Plateau are expected to take the heaviest impact.

"Ultimately, what this study shows is the power of combining massive amounts of satellite imagery with climate models to help better project how our planet will change," said UNC-Chapel Hill Associate Professor of global hydrology Tamlin Pavelsky.

Anti-abortionists 'appropriating' laws that protect same-sex couples and Black citizens

Pro-lifers are using civil rights protections to lobby against early abortions, according to research published in the peer-reviewed journal Sexual and Reproductive Health Matters.

The first known study of its kind has analysed the tactics of anti-abortionists for promoting controversial 'heartbeat' bills. Findings show supporters of these measures, which prohibit terminations from six weeks into pregnancy, are trying to strengthen their case by comparing fetuses to the plight of Black Americans and LGBTQIA people.

New pro-life strategies to restrict abortion include quoting laws designed to protect slaves and same-sex couples, while deliberately misrepresenting medical facts to argue a heartbeat indicates life. This is based on a detailed examination of debates and testimony from pro-life lawmakers and citizens in Georgia, one of nine US states this year to ban terminations once a fetal cardiac activity can be detected.

The researchers say their findings could help opponents devise effective strategies to combat these controversial but growing policies, both in the US and worldwide.

"Early abortion ban legislation is evolving quickly and likely to be replicated in global contexts," says co-author Dr. Dabney P. Evans, Emory University, Atlanta, USA.

"Our analysis provides an initial understanding of evolving early abortion strategy and its tactics for challenging established legal standards and precedent."

"Fetal 'heartbeat' bills have become the anti-abortion legislative measure of choice in the US war on sexual and reproductive health and rights. Comparing the 'heartbeats' of fetuses to historical and current efforts against White supremacy and homophobia demeans the lived experience of those facing such systemic oppressions."

Georgia's 'heartbeat' law was set to become effective in January 2020 after being passed and signed into law in 2019. A temporary injunction has since halted its progress until the courts make a judgement.

The authors set out to identify and characterise the arguments and tactics used by supporters of the state's early abortion ban bill. They analysed video archive debates and testimony from 41 members of two Georgia legislative bodies -- the House Health and Human Services, and Senate Science and Technology committees. Testimony from community members supportive of the bill was also examined.

The researchers identified key themes the bill's backers used to strengthen their case. These included arguing a heartbeat is an indicator of life and therefore personhood. According to the authors supporters used medically inaccurate terms and misconstrued scientific evidence in making this argument.

Another tactic was attempting to create a special class of person -- 'fetuses in utero' -- entitled to legal protection. Some supporters drew parallels between 'unborn children' and civil rights claims by same-sex couples and Black Americans.

They asserted that fetuses should have the same protections as these groups under the 14th Amendment, for example referencing the case of a former slave denied his claim to constitutional protections.

Lobbying for the 'unborn' by adopting the discrimination faced by Black Americans and LGBTQIA people is 'devaluing' the experiences of these groups, say the researchers, and minimises the harm they face.

In some debates, the researchers noted that arguments were made in favour of states using their powers to go beyond federal protections. Supporters called for a 'national standard' that would support fetal rights.

The analysis of the committee hearings identifies how medical science and law was used to further the aims of anti-abortionists. The study highlights facts were misrepresented to add credibility, often by inventing emotive medical-sounding vocabulary eg. 'early infant.'

New Rochelle, NY, December 31, 2019--Before gene therapy can be used to treat renal diseases, delivery of therapeutic genes to the kidney must become much more efficient. A novel approach in which three different gene delivery vectors were injected intravenously and directly into the kidneys of mice was reported in an article published in Human Gene Therapy, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article free on the Human Gene Therapy website through January 31, 2020.

Jeffrey Rubin, Tien Nguyen, Kari Allen, Katayoun Ayasoufi, and Michael Barry of the Mayo Clinic coauthored the article entitled "Comparison of Gene Delivery to the Kidney by Adenovirus, Adeno-Associated Virus, and Lentiviral Vectors after Intravenous and Direct Kidney Injections." As the kidney filters out large compounds from the bloodstream, the researchers chose to study the ability to deliver three different sized vectors via an intravenous route: small adeno-associated virus (AAV) vectors (25 nm), larger adenovirus vectors (100 nm) and lentiviral vectors (120 nm). To bypass this filtering mechanism they also tested two different direct injection routes into the kidney and found these to be superior to intravenous injections. However, some of the vectors were able to leak out of the kidney, creating the possibility for off-target tissue effects. The potential for direct injections opens new possibilities for treating kidney diseases with gene therapy, but additional improvements are needed.

"The great burden of kidney diseases in the U.S .and Europe has yet to be impacted by gene therapy," says Editor-in-Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medi-cal Education and Dean, Provost, and Executive Deputy Chancellor, University of Mas-sachusetts Medical School, Worcester, MA. "The Mayo Clinic team has performed an important head-to-head comparison of currently available gene therapy technology, to identify which may best be used to address this im-portant group of diseases."

Tiny bits of DNA collected from waters off the West Coast allowed scientists to identify more species of marine vertebrates than traditional surveys with trawl nets. They also reflect environmental shifts such as unusual ocean temperatures that affect the organisms present, new research shows.

The findings published in Frontiers in Marine Science demonstrate that environmental DNA, or eDNA, can add valuable detail to longstanding marine surveys. They revealed the presence of important species that usually evade trawl nets such as great white sharks and salmon. Ongoing collection of eDNA can also help detect environmental changes when marine life shifts habitat with changes in the ocean, the study found.

"eDNA is adding details that we might not get any other way, and giving us a more complete picture," said Collin J. Closek, an Early Career Science fellow at the Center for Ocean Solutions at Stanford University. Closek is lead author of the paper with other scientists from Stanford University, University of California Santa Cruz, and NOAA's Southwest Fisheries Science Center.

Increasingly Powerful Genetic Tool

Marine life constantly sheds bits of genetic material into surrounding water. eDNA techniques capture that DNA from water samples and identify the species it comes from. New laboratory sequencing methods help scientists examine many samples at once. They have made eDNA an increasingly powerful tool for detecting the range of species that have passed through the water.

In fact, Closek said that collecting water samples and archiving them can provide a lasting record of the DNA record at a particular place and time. This allows scientists to tap that data years later.

"This helps us most in identifying species distribution," said Elliott Hazen, a research ecologist at the Southwest Fisheries Science Center and coauthor of the study. "With rapid sampling at unprecedented scales, once we understand what it is telling us, we can get a lot of information about marine life across a large area relatively quickly."

The method does not provide all the answers, though. For example, current eDNA sequencing results do not yet allow researchers to count the number or abundance of each species. They do not identify the age or size of the species represented. This means that eDNA will not replace traditional monitoring such as trawl or acoustic surveys any time soon.

Closek and his colleagues worked aboard the NOAA Ship Reuben Lasker in 2016 and 2017. They joined NOAA Fisheries' Rockfish Recruitment and Ecosystem Assessment Survey, which has evaluated the California current forage community since 1983. The eDNA team collected 131 one-liter samples of water in roughly the same places where the ship deployed trawl nets. They collected samples of juvenile rockfish and other forage species. Observers aboard the ship also simultaneously counted the number of marine mammals and seabirds seen during daytime hours. The scientists then compared the results.

It was the first survey of eDNA across such a wide geographic scale on the West Coast.

eDNA Identified Most Species Overall

The trawl surveys identified 28 types of fish over the two years, 11 of which were identified only in the trawl surveys and not by eDNA. By itself, eDNA identified 65 different marine vertebrates, both fish and marine mammals. Together eDNA and trawl surveys identified 80 different fish and marine mammals. They included baleen whales, porpoises, dolphins, seals and sea lions, said John Field, a research fisheries biologist at the Southwest Fisheries Science Center.

"The eDNA analysis detected both the fish and marine mammals in the habitats that we would expect to find them, which gives us greater confidence in the technology to provide accurate details of the species present across the ecosystem," he said. "It may sound basic, but this is an important step in validating this powerful new method of surveying marine life."

Comparing 2016 to 2017, there were differences between the organisms present and their distribution. In 2016 the remnant warmth from a marine heat wave known as "the Blob" was dissipating. Unusual warm-water species were widely spread through West Coast waters.

In 2017, more normal conditions returned. Many of those unusual organisms diminished and eDNA found greater differences between the marine vertebrates present in different areas. These results indicate that eDNA results can help track changes in the environment.

"We don't have the resources to survey everywhere for everything, and eDNA expands our reach," said Alexandria Boehm, a professor in the Department of Civil and Environmental Engineering at Stanford and senior author of the new study. "Now that we know that the methods are in some agreement, it validates the methods so that people feel more confident using eDNA."

As our brains take in information about the world and use it to steer our actions, two key principles guide our choices: seek pleasure and avoid pain. Researchers at Cold Spring Harbor Laboratory (CSHL) have zeroed in on an information-processing hub in the brains of mice to discover how neurons there divide the labor to handle these opposing behavioral motivations.

Their work, reported December 31, 2019 in the journal Neuron, reveals that different classes of neurons control positive and negative motivation, sending opposing signals along a shared motivation-processing brain circuit. Ultimately, the balance of activity between these two groups of cells may determine whether a person acts to seek out pleasurable experiences or avoid negative ones, says CSHL Professor Bo Li, who led the study.

Li wants to understand the brain's motivation-processing circuits because the behaviors they control are often disrupted in people with mental illness. People suffering from depression may stop doing things that once gave them pleasure, for example, whereas people with anxiety disorders may go to greater lengths to avoid potential threats.

The ability to recognize and respond to potential rewards or punishments depends in part on a part of the brain called the ventral pallidum. Researchers have observed activity in this brain region when animals seek rewards, such as a sip of water, or avoid punishments, such as an annoying puff of air. What Li wanted to understand was how the different types of neurons that reside in this part of the brain ensure an animal responds appropriately to signals associated with both types of motivation.

To investigate, his team took advantage of research tools that allowed them to monitor the activity of individual brain cells and to confirm those cells' identities with a flash of light. After training mice to associate certain sounds with either a sip of water or a puff of air, Li and his colleagues used the technique to monitor neural activity in the ventral pallidum. They found that neurons that used the neurotransmitter known as GABA to dampen activity in the circuit influencing motivation were important in motivating the mice to seek a water reward. The neurons that used the neurotransmitter known as glutamate to excite the brain circuit, on the other hand, were essential for avoiding the air-puff punishment.

In more complex situations, where animals were presented with the potential for both punishment and reward, both sets of neurons responded. Mice made different choices in response to the combined stimuli: Thirsty animals, for example, were more willing to risk an air puff to obtain a sip of water than animals that had just drunk their fill. But if the team artificially shifted the balance of activity in the ventral pallidum by manipulating one class of neurons or the other, they could alter the animals' behavior.

That balance between signals that either inhibit or excite neurons in the ventral pallidum appears critical in controlling which motivation an animal acts on, Li says. Now, he is eager to find out whether it is disrupted in people with psychiatric disorders. "Behavioral changes in people with depression or stress-induced anxiety may be caused by changes in this circuit," he says. With the new findings, his team has important leads about how to investigate the causes and symptoms of these disorders more deeply.

Writing in the December 30, 2019 online issue of Neurology, researchers at University of California San Diego School of Medicine and Veterans Affairs San Diego Healthcare System report that accumulating amyloid -- an abnormal protein linked to neurodegenerative conditions such as Alzheimer's disease (AD) -- occurred faster among persons deemed to have "objectively-defined subtle cognitive difficulties" (Obj-SCD) than among persons considered to be "cognitively normal."

Classification of Obj-SCD, which has been previously shown to predict progression to mild cognitive impairment (MCI) and dementia, is determined using non-invasive but sensitive neuropsychological measures, including measures of how efficiently someone learns and retains new information or makes certain types of errors.

The new findings, say authors, suggest that Obj-SCD can be detected during the preclinical state of AD when amyloid plaques are accumulating in the brain, neurodegeneration is just starting, but symptoms of impairment on total scores on thinking and memory tests have not yet been recorded.

"The scientific community has long thought that amyloid drives the neurodegeneration and cognitive impairment associated with Alzheimer's disease," said senior author Mark W. Bondi, PhD, professor of psychiatry at UC San Diego School of Medicine and the VA San Diego Healthcare System. "These findings, in addition to other work in our lab, suggest that this is likely not the case for everyone and that sensitive neuropsychological measurement strategies capture subtle cognitive changes much earlier in the disease process than previously thought possible.

"This work, led by Dr. Kelsey Thomas, has important implications for research on treatment targets for AD, as it suggests that cognitive changes may be occurring before significant levels of amyloid have accumulated. It seems like we may need to focus on treatment targets of pathologies other than amyloid, such as tau, that are more highly associated with the thinking and memory difficulties that impact people's lives."

Study participants were enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI), an on-going effort (launched in 2003) to test whether regular, repeated brain imaging, combined with other biological markers and clinical assessments, can measure the progression of MCI and early AD. Seven hundred and forty-seven persons were involved in this study: 305 deemed cognitively normal, 153 with Obj-SCD and 289 MCI. All underwent neuropsychological testing and both PET and MRI scans.

The research team found that amyloid accumulation was faster in persons classified with Obj-SCD than in the cognitively normal group. Those classified as Obj-SCD also experienced selective thinning of the entorhinal cortex, a region of the brain impacted very early in Alzheimer's disease and associated with memory, navigation and perception of time. Persons with MCI had more amyloid in their brain at the start of the study, but they did not have faster accumulation of amyloid compared to those with normal cognition. However, those with MCI had more widespread temporal lobe atrophy, including the hippocampus.

Broadly speaking, scientists believe that for most people, AD is likely caused by a combination of genetic, lifestyle and environmental factors. Increasing age is a primary, known risk factor. The amyloid hypothesis or amyloid cascade model posits that accumulating amyloid protein plaques in the brain kill neurons and gradually impair specific cognitive functions, such as memory, resulting in AD dementia. However, many scientists are now questioning the amyloid hypothesis given the large number of clinical trials in which drugs targeted and successfully cleared amyloid from the brain but did not impact the trajectory of cognitive decline.

The ability to identify those at risk for AD before significant impairment and before or during the phase of faster amyloid accumulation would be a clinical boon, said authors, providing both a way to monitor disease progression and a window of opportunity to apply potential preventive or treatment strategies.

Currently, both approaches are limited. Some risk factors for Alzheimer's can be minimized, such as not smoking, managing vascular risk factors such as hypertension or following a healthy diet with regular exercise. There are a handful of medications approved for treating symptoms of AD, but as yet, there is no cure.

"While the emergence of biomarkers of Alzheimer's disease has revolutionized research and our understanding of how the disease progresses, many of these biomarkers continue to be highly expensive, inaccessible for clinical use or not available to those with certain medical conditions," said first author Thomas, PhD, assistant professor of psychiatry at UC San Diego School of Medicine and research health scientist at the VA San Diego Healthcare System.

"A method of identifying individuals at risk for progression to AD using neuropsychological measures has the potential to improve early detection in those who may otherwise not be eligible for more expensive or invasive screening."

The thermoelectric conversion efficiency of a particular material is determined by the value of its thermoelectric figure of merit zT. It is a complex function of the absolute temperature and several pertinent transport properties including the Seebeck coefficient, the electrical and thermal conductivities. These quantities are usually measured in parallel to each other, reflecting the longitudinal thermoelectric effect.

Optimization of zT in conventional thermoelectric materials meets severe limitations. For instance, one comes from the charge compensation of electrons and holes that contribute oppositely to the Seebeck effect. The other is the Wiedemann-Franz law that fundamentally ties the electrical and the thermal conductivity, making independent optimization of the two quantities impossible.

A recent paper of J. S. Xiang et al. published in Sci. China-Phys. Mech. Astron. has demonstrated a much larger transverse figure of merit in a topological semimetal in low magnetic fields, relative to its longitudinal counterpart. This simply resembles the much larger transverse (Hall) conductivity over its longitudinal counterpart that is generically observed in many topological semimetals in low fields.

The large transverse zT values in topological semimetal benefit from some of its inherent features. These include the coexistence of electrons and holes which, in the case of transverse thermoelectricity, will contribute additively to each other, and the topologically protected high charge mobility is, to a large extent, free of the lattice imperfection. Actually, the Dirac semimetal Cd3As2, which is focused in this paper, has a very high electron mobility in spite of its negligible lattice thermal conductivity for this reason.

More excitingly, topological semimetals can have excess transverse thermoelectric effect, known as anomalous Nernst effect, arising from the pronounced Berry curvature near the Fermi level. Furthermore, if one considers a magnetic topological semimetal, the large transverse thermoelectricity will appear in the absence of external field.

As the paper reads, the transverse thermoelectric effect offers some more merits over its longitudinal counterpart: one does not need two (n and p) types of thermoelectric materials for constructing one device; because the electrical and thermal currents are orthogonal and decoupled in this case, high electrical conductivity and low thermal conductivity desired for large transverse figure of merit can be easily realized by using an anisotropy compound.

A new study led by researchers at Baylor College of Medicine and published in the Proceedings of the National Academy of Sciences reveals that human noroviruses, the leading viral cause of foodborne illness and acute diarrhea around the world, infect cells of the small intestine by piggybacking on a normal cellular process called endocytosis that cells use to acquire materials from their environment.

The study found that two compounds present in bile - bile acids and the fat ceramide - are necessary for successful viral infection of a laboratory model of the human small intestine. In addition, the researchers report for the first time that bile acids also stimulate endocytosis in the small intestine. The findings support further exploration of the possibility of reducing norovirus infection by modulating the levels of bile acids and/or ceramide.

"Human noroviruses invade cells of the small intestine where they replicate and cause gastrointestinal problems," said co-first author Victoria R. Tenge, graduate student of molecular virology and microbiology in Dr. Mary Estes's laboratory. "Previous work from our lab showed that certain strains of norovirus required bile, a yellowish fluid produced by the liver that helps digest fats in the small intestine. In the current study, we investigated which bile components were involved in promoting norovirus infection."

The researchers worked with human enteroids, a laboratory model of human intestinal cells that retains properties of the small intestine and is physiologically active.

"Mini-guts, as we call them, closely represent actual small intestine tissue, and, importantly, they support norovirus growth, allowing researchers to study how this virus causes disease," said co-first author Dr. Umesh Karandikar, a research scientist in the Estes lab.

Creating a stage that favors viral infection

The researchers discovered that bile acids and ceramide in bile were necessary for viral infection.

"Interestingly, we also discovered that bile acids stimulated the process of endocytosis in mini-guts. Our findings led us to propose that as bile acids activate endocytosis, they create a stage that norovirus takes advantage of by riding along with it to enter the cells and subsequently replicate, causing disease," said corresponding author, Dr. Mary K. Estes, Cullen Foundation Endowed Professor Chair of Human and Molecular Virology at Baylor College of Medicine and emeritus founding director of the Texas Medical Center Digestive Diseases Center. "Bile acid-induced endocytosis in the small intestine was not previously appreciated."

"This strategy works well for a food-borne virus," said co-first author Dr. Kosuke Murakami, who was working in the Estes lab during most of this project. He is currently at the National Institute of Infectious Diseases in Tokyo. "As people ingest food, the body's normal response is to secrete bile into the small intestine. Noroviruses contaminating food piggyback on this natural bodily response to invade cells in the small intestine, replicate and cause disease."

Working with mini-guts not only showed new insights into how norovirus causes disease, but also illuminated details about the basic biological process of endocytosis in the small intestine that had not been reported before.

"Our findings suggest the possibility that modulating the amount of bile acids and/or ceramide could help reduce norovirus infection," Tenge said.

"This strategy might be particularly helpful to people who have norovirus infections for months, even years," Karandikar said.

For sick or prematurely born babies spending their first days of life in a hospital's neonatal intensive care unit (NICU), the soothing voice and gentle touch of a loving parent can have a tremendous impact toward a positive outcome -- that is, unless mom or dad's visit leaves the infant with something extra: a dangerous bacterial infection.

Now, a Johns Hopkins Medicine research team reports it has developed and tested a relatively simple strategy for reducing the chance of parents exposing their babies in the NICU to one of the most commonly diagnosed and potentially deadly microbial scourges in a hospital: Staphylococcus aureus. The researchers detailed the positive findings from their preliminary clinical trial in the Dec. 30, 2019, online posting by the Journal of the American Medical Association (JAMA).

"Traditional procedures for preventing hospital-acquired Staph infections in the NICU have primarily focused on keeping staff and facilities as sterile as possible," says Aaron Milstone, M.D., M.H.S., associate hospital epidemiologist at the Johns Hopkins Hospital, professor of pediatrics at the Johns Hopkins University School of Medicine and lead author of the JAMA paper. "Our study is among the first to focus on parents as a source of the bacteria and then test the effectiveness of an intervention to combat the problem."

According to the U.S. Centers for Disease Control and Prevention, an estimated 30% of the adult population are long-term carriers of Staphylococcus aureus bacteria. Most of the time, these people are healthy and the microorganisms they harbor cause no harm. However, in healthcare settings where patients may have weakened immune systems, the bacteria can become a serious, even deadly, threat. An unchecked spread of the bacteria -- both the antibiotic-susceptible and antibiotic-resistant (such as methicillin-resistant Staphylococcus aureus, or MRSA) strains -- can lead to severe complications, including bacteremia or sepsis (blood infections), pneumonia, endocarditis (heart valve infection) and osteomyelitis (bone infection).

In the NICU, S. aureus infections not only threaten a sick or premature infant's survival but their neurological development as well. In a 2015 study, Milstone and others estimated that there are more than 5,000 cases of invasive S. aureus infections each year in NICUs across the nation and that 10% of the children will likely die before hospital discharge.

To reduce the spread of S. aureus, the Johns Hopkins Medicine researchers turned to a simple regimen for mothers and fathers to follow while their child is in intensive care. The preventive measure includes the application of an antibiotic (mupirocin) ointment into the nose and skin cleansing with a wipe containing 2% chlorhexidine gluconate, an antiseptic widely used on patients to remove surface bacteria around a surgical site before an operation.

The Treating Parents to Reduce NICU Transmission of S. aureus (TREAT Parents) clinical trial was conducted to test the proposed strategy's effectiveness. The researchers selected for study 190 newborn babies admitted to two NICUs at Johns Hopkins-affiliated hospitals in Baltimore, Maryland, between November 2014 and December 2018. Each of the infants had at least one parent who tested positive for S. aureus when screened at the time of their child's entry into the NICU. Baseline S. aureus counts were done for the infants at the same time.

The parents of 89 babies self-administered the antibiotic nasal ointment twice a day for five days and cleaned designated skin areas (hands, arms, legs, chest, neck, back and the skin between the buttocks and groin) with antiseptic wipes for the same time period. The control group, consisting of the remaining 101 parental couples, used identically packaged placebo treatments of petroleum jelly and non-antiseptic wipes.

Both sets of babies were monitored for S. aureus colonization until discharge from the NICU. Bacteria recovered from the infants were analyzed to determine if they were the same strain as seen in at least one parent.

Among the 190 infants studied overall, 42, or about 22%, acquired S. aureus that matched bacteria recovered from either their mother or father, or from both parents. In this group, four babies had MRSA strains acquired from a parent.

Of the 101 babies with parents in the control group, 29 (nearly 29%) had parentally acquired bacteria compared with only 13 of the 89 babies (nearly 15%) whose parents were given actual antibiotic ointment and antiseptic wipes to use.

"These results from our preliminary trial indicate that treatment with intranasal mupirocin and chlorhexidine wipes may significantly reduce the number of infants in the NICU who will get S. aureus from contact with a parent," Milstone says. "It is our hope that one day this technique can be combined with personal cleanliness for medical staff and environmental safety protocols for facilities to provide a stronger defense against NICU-acquired infections."

Before that goal can be reached, Milstone says, larger clinical trials are needed to replicate and validate these findings, along with determining whether the parental cleanliness protocol should be applied to the families of all infants in the NICU or just those with babies at greatest risk. He adds that this research should be followed by efforts to refine the procedure to optimize its effectiveness and ease of use.

The callers pretended to be well-meaning parents who were trying to safely dispose of unneeded antibiotics and opioid-based prescription painkillers after their child's surgery. Fewer than half of the California pharmacies they called provided correct prescription drug disposal details, a percentage that dropped sharply if the "secret shoppers" made their call on a weekend, according to a brief research report published online Dec. 31, 2019, in Annals of Internal Medicine.

"The Food and Drug Administration advises consumers about how to safely dispose of unneeded medicines and, because pharmacists can play an integral role in this conversation, the American Pharmacists Association says prescription medication disposal should follow FDA guidelines," says Rachel E. Selekman, M.D., MAS, a pediatric urologist at Children's National Hospital and the study's lead author. "We found very few California pharmacies permitted take-back of unneeded medications. There was also a striking difference in the accuracy and completeness of drug disposal information depending on whether they answered the call on a weekday or a weekend. That suggests room for improvement," Dr. Selekman says.

The multi-institutional research team, led by Primary Investigator and senior author Hillary L. Copp, M.D., MS, at University of California, San Francisco, identified licensed pharmacies located in urban and rural settings in California. That state that accounts for 10% of all U.S. pharmacies. They wrote a script that guided four male and two female "secret shoppers" to ask about what to do about leftover antibiotics (sulfamethoxazole-trimethoprim tablets) and a liquid opioid-based painkiller (hydrocodone-acetaminophen). From late-February to late-April 2018, they called 898 pharmacies from 8 a.m. to 8 p.m., asking about the correct way to dispose of these medicines.

According to the FDA, consumers should mix most unused medicines with an unappealing substance, like kitty litter, place it in a sealed container and toss the container in the trash. Medicines that can be harmful to others, like opioids, should be flushed down the sink or toilet. Many pharmacies have programs or kiosks to handle unused prescription medicines.

Of the pharmacies surveyed in California:

389 (47%) provided correct information about disposing of antibiotics

251 (29%) provided correct information about how to dispose of both antibiotics and opioids

204 (19%) provided correct information about how to dispose of opioids

49% provided correct antibiotic disposal information and 20% provided correct opioid disposal information on weekday calls

15% provided correct antibiotic disposal information and 7% provided correct opioid disposal information on weekend calls

Asked specifically about drug take-back programs, just 11% said their pharmacy had one that could be used to dispose of antibiotics or opioids.

"Unused prescription medications can be misused by others and can result in accidental childhood poisonings," Dr. Selekman adds. "The bottom line is that we often talk about how to address the problem of too many unused medications lingering in homes. There are many reasons this is a problem, but part of the problem is nobody knows what to do if they have too many prescription medicines. Because of this research, we have discovered that pharmacies don't uniformly provide accurate information to our patients. Patients, families and health care professionals who advise families should work together to help improve and expand safe disposal options for these powerful medications."

Research on fossilized fish from the late Devonian period, roughly 375 million years ago, details the evolution of fins as they began to transition into limbs fit for walking on land.

The new study by paleontologists from the University of Chicago, published this week in the Proceedings of the National Academy of Sciences, uses CT scanning to examine the shape and structure of fin rays while still encased in surrounding rock. The imaging tools allowed the researchers to construct digital 3D models of the entire fin of the fishapod Tiktaalik roseae and its relatives in the fossil record for the first time. They could then use these models to infer how the fins worked and changed as they evolved into limbs.

Much of the research on fins during this key transitional stage focuses on the large, distinct bones and pieces of cartilage that correspond to those of our upper arm, forearm, wrist, and digits. Known as the "endoskeleton," researchers trace how these bones changed to become recognizable arms, legs and fingers in tetrapods, or four-legged creatures.

The delicate rays and spines of a fish's fins form a second, no less important "dermal" skeleton, which was also undergoing evolutionary changes in this period. These pieces are often overlooked because they can fall apart when the animals are fossilized or because they are removed intentionally by fossil preparators to reveal the larger bones of the endoskeleton. Dermal rays form most of the surface area of many fish fins but were completely lost in the earliest creatures with limbs.

"We're trying to understand the general trends and evolution of the dermal skeleton before all those other changes happened and fully-fledged limbs evolved," said Thomas Stewart, PhD, a postdoctoral researcher who led the new study. "If you want to understand how animals were evolving to use their fins in this part of history, this is an important data set."

Seeing ancient fins in 3D

Stewart and his colleagues worked with three late Devonian fishes with primitive features of tetrapods: Sauripterus taylori, Eusthenopteron foordi and Tiktaalik roseae, which was discovered in 2006 by a team led by UChicago paleontologist Neil Shubin, PhD, the senior author of the new study. Sauripterus and Eusthenopteron were believed to have been fully aquatic and used their pectoral fins for swimming, although they may have been able to prop themselves up on the bottom of lakes and streams. Tiktaalik may have been able to support most of its weight with its fins and perhaps even used them to venture out of the water for short trips across shallows and mudflats.

"By seeing the entire fin of Tiktaalik we gain a clearer picture of how it propped itself up and moved about. The fin had a kind of palm that could lie flush against the muddy bottoms of rivers and streams," Shubin said.

Stewart and Shubin worked with undergraduate student Ihna Yoo and Justin Lemberg, PhD, another researcher in Shubin's lab, to scan specimens of these fossils while they were still encased in rock. Using imaging software, they then reconstructed 3D models that allowed them to move, rotate and visualize the dermal skeleton as if it were completely extracted from the surrounding material.

The models showed that the fin rays of these animals were simplified, and the overall size of the fin web was smaller than that of their fishier predecessors. Surprisingly, they also saw that the top and bottom of the fins were becoming asymmetric. Fin rays are actually formed by pairs of bones. In Eusthenopteron, for example, the dorsal, or top, fin ray was slightly larger and longer than the ventral, or bottom one. Tiktaalik's dorsal rays were several times larger than its ventral rays, suggesting that it had muscles that extended on the underside of its fins, like the fleshy base of the palm, to help support its weight.

"This provides further information that allows us to understand how an animal like Tiktaalik was using its fins in this transition," Stewart said. "Animals went from swimming freely and using their fins to control the flow of water around them, to becoming adapted to pushing off against the surface at the bottom of the water."

Stewart and his colleagues also compared the dermal skeletons of living fish like sturgeon and lungfish to understand the patterns they were seeing in the fossils. They saw some of the same asymmetrical differences between the top and bottom of the fins, suggesting that those changes played a larger role in the evolution of fishes.

"That gives us more confidence and another data set to say these patterns are real, widespread and important for fishes, not just in the fossil record as it relates to the fin-to-limb transition, but the function of fins broadly."