Culture

(Boston)-- Researchers from Boston University School of Medicine, working with scientists across the nation on the Alzheimer's Disease Sequencing Project (ADSP), have discovered new genes that will further current understanding of the genetic risk factors that predispose people to the development of Alzheimer's disease (AD). The ADSP was developed by the National Institutes of Health (NIH) in response to the National Alzheimer's Project Act milestones to fight AD.

The incidence of AD is increasing each year and is the most common cause of dementia. Also, it is the fifth leading cause of death in those 65-years and older, according to the CDC. AD is characterized by the formation of senile plaques (extracellular deposits of β-amyloid protein) and neurofibrillary tangles (aggregates of hyper-phosphorylated tau protein) in the brain, leading to neurodegeneration and decline in memory, and eventually death. Despite the growing prevalence of AD and cost to society, the genetic and environmental factors that make some more susceptible to the development of AD is still not well understood.

"This large and deep gene sequencing study is an important part of identifying which variations may play a part in risk of getting Alzheimer's or protection against it," said Eliezer Masliah, MD, director of the Division of Neuroscience at the National Institute on Aging, part of NIH. "Big data efforts like the ADSP are really helping research move forward. Identifying rare variants could enhance our ability to find novel therapeutic targets and advance precision medicine approaches for Alzheimer's disease."

By comparing the exomes (gene-coding portions of entire genetic sequences) of nearly 6,000 individuals with AD and 5,000 cognitively healthy older adults, the researchers were able to find rare variations in genes that they believe may contribute to the development of common AD. These newly discovered genes may suggest an inflammatory response and changes in the protein production. These combined changes are thought to contribute to the overall neurodegeneration witnessed in AD.

The researchers hope their work will help bridge the knowledge gaps of the genetic architecture related to AD, which is a necessary step toward a better understanding of mechanisms leading to AD and eventual therapeutic treatments. "Many of our findings will provide insight into disease mechanisms and targets for biological experiments to gain further understanding about the role of these genes in AD pathogenesis," explained corresponding author Lindsay A. Farrer, PhD, Chief of Biomedical Genetics and a professor of Medicine, Neurology, Ophthalmology, Epidemiology and Biostatistics at Boston University Schools of Medicine and Public Health.

The research team emphasizes that further research will need to be done to find other genes hidden throughout the genome, as the current paradigm is that many genes contribute to the development of AD.

An undergraduate researcher has developed a method to screen frogs for an infectious disease that has been linked to mass die-offs of frogs around the world. Thanks to her method, scientists will be able to track the disease and try to figure out why it is triggering the deaths.

Emily Karwacki, who recently earned her biology degree from the University of Central Florida, didn't set out to track the deadly pathogen Perkinsea, but after landing a research spot in Assistant Professor Anna Savage's lab, she was set with the task of trying to test for the disease. Frogs, which are indicators of environmental changes, have been dying off in mass quantities. They are also an important part of the food chain. Without frogs, many other species would die, Savage said.

Scientists have narrowed down what's most affecting frogs to three pathogens, including Perkinsea.

"Not a lot of people have studied Perkinsea because it has only recently been identified," Karwacki said. "It's different from other diseases because of the way it attacks the host."

The pathogen enters the frog through the skin or may be ingested through its mouth. Scientists know it goes straight to the liver, embedding itself, before moving onto the rest of the tissue. It spreads and then the frog dies.

Karwacki, along with Savage and doctoral student Matt Atkinson, suspected that Perkinsea was killing frogs in Central Florida, but the researchers needed a way to test for it first. Karwacki was tasked with creating the molecular test. The method is called qPCR, but because Perkinsea was newly discovered, there wasn't enough genetic data to make a specific test. Karwacki had to create what's called a primer pair, and match it with a DNA sequence of Perkinsea, to get the qPCR test to work.

"The test amplifies the DNA so you know if your pathogen is there or not," Emily said. "I had to align a bunch of DNA sequences from our samples with others from around the word to create my primer set. It was four or five months before we had both the primers and the probe to create a successful test."

Karwacki was the first to do this for Perkinsea and her work was recently published in the journal Diseases of Aquatic Organisms.

Using Karwacki's qPCR assay, the team of researchers found that 25 percent of the frogs they sampled tested positive for the pathogen. They sampled three sites in Florida: Gold Head Branch State Park in Keystone Heights, the UCF Arboretum in Orlando, and the Archbold Biological Station in Venus. The area they found with the most prevalent infection was Gold Head Branch, which is the farthest north. Archbold, the farthest south, had no infection at all.
"There are only three papers on this disease that identify it specifically," Karwacki said. "It has greatly been affecting amphibians in the southeastern United States and should be studied more. It's most likely at least a co-factor in these extinction events we are seeing."

Karwacki's method will now allow researchers all over the world to test for the disease. After graduating this summer, she is working on a new study, swabbing frog tissue samples at the Florida Museum of Natural History in Gainesville. She's swabbed more than 900 samples, and has found that Perkinsea dates back to 1922. This proves the disease has been in frog populations before, and scientists are trying to figure out why it's only now killing off large numbers of frogs.
"Now with my qPCR, people can test areas where they are trying to release frogs to rebound populations," Karwacki said. "Scientists can test water and soil to see if Perkinsea is there so we don't send frogs out to die."

Karwacki is entering the nonprofit business management master's program at UCF before pursuing graduate school. She will continue her work as a research associate in Savage's lab.

COLUMBUS, Ohio - Researchers have found a surprising new explanation of how young brains are shaped for sexual behavior later in life.

Immune cells usually ignored by neuroscientists appear to play an important role in determining whether an animal's sexual behavior will be more typical of a male or female, according to research led by Kathryn Lenz, an assistant professor of psychology and neuroscience at The Ohio State University.

The study, which was done in rats, appears in the Journal of Neuroscience.

To better understand the role of the mast cells in sexual behavior, Lenz and her colleagues silenced the cells in male fetal rats and then observed the rats' development later in life.

The researchers paired one of these male animals with a female that was receptive to mating and watched to see whether the male sexually pursued the female - basically, whether he chased her and mounted her.

The experimental males were far less interested than typical males, acting almost like females.

The researchers also manipulated female newborn rats, activating the mast cells with a stimulating chemical.

As adults, they acted like males.

"It's fascinating to watch, because these masculine females don't have the hardware to engage in male reproductive behavior, but you wouldn't know it from the way they act," said Lenz, a researcher in Ohio State's Institute for Behavioral Medicine Research. "They appear to be strongly motivated to try to engage in male sexual behavior with other females."

The researchers found that estrogen (which plays a major role in development of masculine traits in rats) activates mast cells in the brain and that those mast cells drive the animal's sexual development.

Though scientists know that sex differences are programmed by hormones during early development, they have limited information about the cellular-level changes that contribute to the manner in which the brain and behavior are formed.

"We're really interested in the fundamental mechanisms that drive brain development and sex-specific brain development, and this study found that mast cells - immune cells involved in allergic responses - play a key role," Lenz said.

If human development mirrors what was seen in this animal study, it's possible that relatively minor influences - such as an allergic reaction, injury or inflammation during pregnancy - could steer sexual behavior development in offspring, Lenz said. It's even conceivable that taking antihistamines or pain relievers during pregnancy could play a role, she said.

Furthermore, this discovery could help explain risks for psychiatric and neurological disorders that are more common in males, including autism, she said.

"These mast cells in the brain appear crucial for life-long brain development, even though there are relatively few of them, and this should really open our eyes to the potential role of different immune cells in the human brain. There's so much we don't know, and we need to pay attention to all the cells in the brain and how they talk to each other," she said.

The study focused on the pre-optic area of the brain, which is part of the hypothalamus.

"This is the most sexually dynamic area of the brain - we know that it's highly important for male-type reproductive and social behaviors such as mounting and for initiating maternal behavior in female animals," Lenz said.

Previous work by the researchers uncovered the role of another type of brain cell, microglia, in directing sexual behavior. In the new study, they found that mast cells activate the microglia.

"This new mast cell discovery is really one of those accidents of science," Lenz said, explaining that another researcher was conducting some unrelated work on sex differences in gene expression and noticed that there appeared to be some differences in mast cell genes depending on whether the brains were from a male or female.

In addition to the behavioral changes documented in the study, the researchers examined cellular-level changes as well. Female newborn rats exposed to a dose of the masculinizing hormone estrogen had an increase in mast cells in the brain. Those cells released histamine, which stimulated other brain cells (the microglia) to activate male-typical brain patterning.

Scientists at The University of Texas Health Science Center at Houston (UTHealth) have identified the brain networks that allow you to think of an object name and then verbalize that thought. The study appeared in the July issue of BRAIN. It represents a significant advance in the understanding of how the brain connects meaning to words and will help the planning of brain surgeries.

Their discovery could help explain why people with neurodegenerative disease often forget the names of objects. An estimated 5.7 million Americans of all ages have Alzheimer's dementia. Described as the tip-of-the-tongue phenomenon in healthy individuals, the inability to recall the name of items is a condition called anomia.

"Object naming has been a core method of study of anomia, but the processes that occur when we come up with these names, generally in less than a second, are not well understood. We mapped the brain regions responsible for naming objects with millimeter precision and studied their behavior at the millisecond scale," said Nitin Tandon, M.D., the study's senior author and a professor in the Vivian L. Smith Department of Neurosurgery at McGovern Medical School at UTHealth.

"The role of the basal temporal lobe in semantic processes has been underappreciated. Surgeons could use this information to design better approaches for epilepsy and tumor surgery, and to reduce the cognitive side effects of these surgical procedures," said Tandon, who is also the director of the epilepsy program with the Memorial Hermann Mischer Neuroscience Institute-Texas Medical Center and a member of the faculty at The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences.

Tandon added that this study is of particular value as it produced convergent maps with three powerful techniques: electrophysiology, imaging and brain stimulation.

While their brain activity was being monitored for epileptic seizures, 71 patients were asked to look at a picture of an object and identify it and/or asked to listen to a verbal description of an object and name it. Much like explorers mapped the wilderness, the researchers used these brain data to map out the brain networks responsible for certain processes.

With the aid of both electrocorticography and functional magnetic resonance imaging, researchers zeroed in on the specific brain regions and networks involved in the naming process. This was then confirmed with a pre-surgical mapping technique called direct cortical stimulation that temporarily shuts down small regions of the brain.

"The power of this study lies in the large number of patients who performed name production via two different routes and were studied by three distinct modalities," said Kiefer Forseth, the study's lead author and an M.D./Ph.D. student at MD Anderson UTHealth Graduate School.

Historically, water managers throughout the thirsty state of California have relied on hydrology and water engineering -- both technical necessities -- as well as existing drought and flood patterns to plan for future water needs.

Now, climate change is projected to shift water supplies as winters become warmer, spring snowmelt arrives earlier, and extreme weather-related events increase. Some water utilities have started to consider these risks in their management, but many do not. Lack of climate change adaptation among water utilities can put water supplies and the people dependent on them at risk, especially in marginalized communities, a new University of California, Davis, paper suggests.

The paper, which analyzes various approaches to climate science by drinking water utility managers in California, was presented along with new research at the American Sociology Association Conference in Philadelphia on Aug. 11. The paper, "Climate Information? Embedding Climate Futures within Social Temporalities of California Water Management," was published this spring in the journal Environmental Sociology.

Timely study

"Recent events and political conversation around water management and climate change in California makes this study especially timely," said Zeke Baker, a UC Davis doctoral candidate and lead author of the study.
To conduct the study, Baker worked with co-authors and additional researchers in 2016 to interview 60 water managers. These managers were selected as a sample of the more than 3,000 water utilities in California.

Some look closely at climate change, others disregard

"We found significant variation in how water managers engage with climate information," Baker said. "A finding we didn't expect is that perspectives and experiences of water utility managers clustered in cultural terms, regarding how they understand the future." The authors label these "social temporalities" in order to bring attention to alternative ways that water managers view climate change and the future generally. Based on the interviews, the researchers found three types of manager's temporalities, or philosophies.

One type were those water managers who "modeled futures," or looked closely at climate change to anticipate and plan for water needs. Those were generally large metropolitan utilities with multiple resources and access to expertise, researchers noted. For them, envisioning uncertain futures 30 years out is a matter of course.

In the half century since the birth of the women's movement in the West in the 1960s, support for gender equality has spread around the globe -- but in uneven ways. A multinational study by University of California, Davis, sociologists charts three distinct transitions in gender attitudes associated with national characteristics.

Professor Xiaoling Shu and graduate students Bowen Zhu and Kelsey Meagher used two-step machine learning to analyze data from the World Values Survey on more than 70,000 people in 47 countries -- the largest number of countries ever studied on gender attitudes -- to compare support for women's rights as well as support for women combining work and family.

They will present the study, "Classifying and Mapping Gender Ideologies Globally: Gender Attitudes in 47 Countries," in Philadelphia at the 113th Annual Meeting of the American Sociological Association (ASA) on Aug. 14.

The researchers compared gender attitudes with individual variables such as gender, income, education and religion, as well three country-level influences: economic development, women's economic independence and workforce participation.

They found the highest support for equal rights and gender roles in countries with the highest rates of women participating in the labor force.

"Although economic development has liberalized attitudes toward gender equality, it has not led to growing support for women's dual roles as mothers and workers, largely due to the policies of liberal and conservative welfare states which are based on a male breadwinner model and provide little institutional support for working women," the authors conclude.

"On the other hand, despite high levels of women as primary wage earners and strong maternity provision in former socialist countries, women's paid employment has not routinely led to beliefs about their equal rights and status with men."

They identified three distinct trajectories of transition in gender attitudes away from traditional patriarchal views:

The first taken by the social democratic countries of Finland, Sweden and Norway is characterized by high economic development, high rates of women's labor force participation and high levels of women's economic independence. These features promote a highly egalitarian gender ideology toward women's rights and dual mother-worker roles.

The second trajectory taken by liberal and conservative Western countries such as the United States, Germany and New Zealand are characterized by economic wealth, modest rates of women's labor force participation, fewer women as chief wage earners and meager maternity provisions. This combination produces a liberal individualist ideology, endorsing women's equality with men while subjecting women to culturally prescribed expectations of intensive mothering.

The last route has been taken by former socialist states such as Russia, China and Romania, which features far less economic development, a high degree of women as chief wage earners and decent maternity leave provisions. These characteristics foster an ideology that upholds male supremacy.

Previous studies have been mixed on the links between women's labor participation and gender attitudes. They examined only a few industrialized countries and didn't control for other national characteristics.

"Our analysis shows that people in countries with high rates of women's employment strongly endorse women's equal rights and dual roles," Shu and colleagues write.

They found that a country's wealth, as measured by gross national product, fosters support for gender equality but diminishes approval for women's dual work/family roles.

Conversely, women's economic independence, by itself, has a different effect from GDP per capita. In countries with high proportions of female breadwinners and generous childcare leave provisions, support rose for women working to support their families but it is not associated with endorsement for women to gain equal rights and opportunities.

Sometimes, even in the more liberal nations, attitudes reverse direction.

In another study, presented at an ASA meeting in 2014 and recently published in the journal Social Forces, Shu and Meagher found that declining support for gender equality in the United States in the 1990s and early 2000s corresponds to a rise of professional men working long hours and women picking up the slack in caring for home and family.

Shu and Zhu will present the new research findings during a 10:30 a.m.-12:10 session on globalization, immigration and gender at the Philadelphia Marriott Downtown, Level 5, Salon H, on Tuesday, Aug. 14.

RIVERSIDE, Calif. -- A team of astronomers led by George Becker at the University of California, Riverside, has made a surprising discovery: 12.5 billion years ago, the most opaque place in the universe contained relatively little matter.

It has long been known that the universe is filled with a web-like network of dark matter and gas. This "cosmic web" accounts for most of the matter in the universe, whereas galaxies like our own Milky Way make up only a small fraction. Today, the gas between galaxies is almost totally transparent because it is kept ionized-- electrons detached from their atoms--by an energetic bath of ultraviolet radiation.

Over a decade ago, astronomers noticed that in the very distant past -- roughly 12.5 billion years ago, or about 1 billion years after the Big Bang -- the gas in deep space was not only highly opaque to ultraviolet light, but its transparency varied widely from place to place, obscuring much of the light emitted by distant galaxies.

Then a few years ago, a team led by Becker, then at the University of Cambridge, found that these differences in opacity were so large that either the amount of gas itself, or more likely the radiation in which it is immersed, must vary substantially from place to place.

"Today, we live in a fairly homogeneous universe," said Becker, an expert on the intergalactic medium, which includes dark matter and the gas that permeates the space between galaxies. "If you look in any direction you find, on average, roughly the same number of galaxies and similar properties for the gas between galaxies, the so-called intergalactic gas. At that early time, however, the gas in deep space looked very different from one region of the universe to another."

To find out what created these differences, the team of University of California astronomers from the Riverside, Santa Barbara, and Los Angeles campuses turned to one of the largest telescopes in the world: the Subaru telescope on the summit of Mauna Kea in Hawaii. Using its powerful camera, the team looked for galaxies in a vast region, roughly 300 million light years in size, where they knew the intergalactic gas was extremely opaque.

For the cosmic web more opacity normally means more gas, and hence more galaxies. But the team found the opposite: this region contained far fewer galaxies than average. Because the gas in deep space is kept transparent by the ultraviolet light from galaxies, fewer galaxies nearby might make it murkier.

"Normally it doesn't matter how many galaxies are nearby; the ultraviolet light that keeps the gas in deep space transparent often comes from galaxies that are extremely far away. That's true for most of cosmic history, anyway," said Becker, an assistant professor in the Department of Physics and Astronomy. "At this very early time, it looks like the UV light can't travel very far, and so a patch of the universe with few galaxies in it will look much darker than one with plenty of galaxies around."

This discovery, reported in the August 2018 issue of the Astrophysical Journal, may eventually shed light on another phase in cosmic history. In the first billion years after the Big Bang, ultraviolet light from the first galaxies filled the universe and permanently transformed the gas in deep space. Astronomers believe that this occurred earlier in regions with more galaxies, meaning the large fluctuations in intergalactic radiation inferred by Becker and his team may be a relic of this patchy process, and could offer clues to how and when it occurred.

"There is still a lot we don't know about when the first galaxies formed and how they altered their surroundings," Becker said.

By studying both galaxies and the gas in deep space, astronomers hope to get closer to understanding how this intergalactic ecosystem took shape in the early universe.

In the first study of its kind, researchers characterized the skin microbiome of a population of free-ranging snakes to begin to understand how the animals' environmental microbial community may promote disease resistance as well as how it may be disrupted by infection.

The study, which was recently published in Scientific Reports, a Nature research journal, focused on eastern massasaugas in Illinois. This species of endangered rattlesnake is highly susceptible to the fungal pathogen Ophidiomyces ophiodiicola, which causes snake fungal disease (SFD). SFD results in disfiguring sores on snake skin, has a high mortality rate, and poses a significant threat to snake populations in North America and Europe. The mechanism by which the pathogen causes disease is unknown.

"Globally, fungal pathogens are increasingly associated with wildlife epidemics, such as white-nose syndrome in bats and chytridiomycosis in amphibians," said Dr. Matt Allender, a faculty member at the University of Illinois College of Veterinary Medicine and an affiliate of the Illinois Natural History Survey (INHS), part of the university's Prairie Research Institute. "Snake fungal disease has been identified in a number of snake species, but very little is known about contributing factors for infection."

Dr. Allender, who heads the Wildlife Epidemiology Laboratory, has been investigating SFD for more than 8 years. In 2014 he introduced a quantitative polymerase chain reaction (qPCR) test to quickly identify the fungus from a swabbed sample.

"In a 20-year collaborative study led by INHS researchers, we have been the primary investigator of numerous studies documenting disease trends in the eastern massasauga including overall health, but none of these health parameters seemed to explain the emergence of SFD. This study was undertaken in light of recent promising findings about the importance of environmental microbial communities in animal and human health."

Based on their analysis of 144 skin swabs collected from 44 snakes in 2015 and 52 snakes in 2016, all near Carlyle Lake, Ill., researchers determined that infection with SFD altered the bacterial and fungal diversity of the snakes studied. On the infected snakes, Ophidiomyces was present even at locations on the snakes' bodies distant to the open sores, indicating that the skin's entire microbiome is altered by the infection.

No Ophidiomyces spores were detected on SFD-negative snakes, as would have been expected had those snakes' microbiome proven protective against the pathogen.

Findings related to the specific bacteria and fungi found in greater or lesser abundance depending on the disease status of the snake are detailed in the study.

The researchers believe their findings will have broad relevance to other snake species and habitats and will provide insight into mechanisms of pathogen emergence, fluctuations in wellness of individuals, and development of therapeutic interventions.

Lipid droplets: they were long thought of merely as the formless blobs of fat out of which spare tires and muffin tops were made. But these days, they're "a really hot area of research," says Michael Welte, professor and chair of biology at the University of Rochester.

That's in part because lipid droplets have been found to play critical roles in the life cycles of certain proteins involved in gene expression. Now, a study by Welte and his colleagues, published in the journal eLife, describes how lipid droplets regulate these proteins. The research has implications for understanding what helps embryos survive and could cause us to reconsider how we look at lipid-related diseases like obesity.

BEYOND FAT STORAGE

You may not know it, but whenever you eat cheese, ice cream, or yogurt, you are also ingesting microscopic lipid droplets.

"The mammary gland cells that make milk make lots of lipid droplets and then secrete those," says Welte. "Any dairy product or animal product that we consume is full of lipid droplets."

Lipid droplets perform functions in various parts of the human body: in the liver, they store vitamin A; in the retina of the eye, they help store the pigment that cells use to recognize light. They are even in the sebaceous glands, which make the oily material that covers our hair and skin.

But lipid droplets aren't just fat deposits. According to Welte, recent research found that lipid droplets have three main functions beyond their roles in fat storage:

-Maturation: Some proteins, when they are first made, need lipid droplets to achieve their mature form.

-Breakdown: Lipid droplets keep certain proteins out of the way when the proteins are either damaged or obsolete but are not yet destroyed.

-Storage: Lipid droplets act as storage units for various proteins, so the proteins are sequestered until they are needed elsewhere in the cell.

'PACEMAKERS' FOR HISTONES

Welte's current research uses fruit fly embryos to study how lipid droplets influence a particular set of proteins called histones. Histones are present in many organisms, from yeast to fruit flies to humans, and are responsible for wrapping long strands of DNA so the DNA will fit into a cell's nucleus. Fruit flies embryos are ideal to study because they duplicate their DNA about every 10 minutes, and, as a result, need large quantities of histones.

Histones are essential to life for most organisms "because they control everything in the nucleus and package DNA to regulate gene expression," Welte says. "If we have the wrong amount of histones--either too many or too few--there will be widespread defects."

If there are too few histones, genes might be expressed that shouldn't be. Too many histones can cause cells to have trouble dividing their chromosomes.

Welte discovered that lipid droplets play an important role in regulating a particular histone called H2Av. A mother fly produces huge amounts of histones, which are then transferred to her eggs so an embryo's DNA can be packaged as the embryo develops and makes more cells. Acting like pacemakers, the lipid droplets regulate how fast H2Av enters a cell's nucleus by storing the H2Av until the nucleus needs it.

The researchers used sophisticated microscopy to observe exactly how lipid droplets keep out H2Av. Welte and his colleagues discovered, to their surprise, that the storage function is not static--histones don't stay on the droplets all the time. Instead, the H2Av molecules are constantly shuffled back and forth between lipid droplets. The exchange allows the fruit fly embryo to always have free H2Av available to transport into the cell nucleus, but at the same time keeps the concentration of free H2Av low so that it is transported to the nucleus at a slower pace--a pace more in sync with the speed of DNA synthesis.

The researchers also showed that the regulating function is turned off in the fruit fly embryo once the embryo reaches a particular stage, indicating that cells can control when to employ the protein-handling function of lipid droplets.

EMBRYO SURVIVAL AND LIPID-RELATED DISEASES

Identifying these functions of lipid droplets gives researchers more insight into how embryos develop and survive: without lipid droplets regulating H2Av, embryos can become compromised.

What we now know about the various functions of lipid droplets also means that researchers need to consider these factors when examining the effects of obesity. Lipid droplets are dysfunctional in disease states like obesity (too many lipid droplets) or lipodystrophies (too few lipid droplets), Welte says. "The cause of these diseases--too much or too little fat--has to do with how much lipid you have. Our work suggests that when looking at these disease states, people also need to look at what happens to the proteins, because these lipids droplets have this second function beyond handling fat."

Improved compensation, expanded mentorship and training opportunities, and concrete measures to improve workforce diversity are all needed to address attrition from the ranks of physician scientists specializing in infectious diseases, and to ensure that the next generation of that work force is sufficient to bring quests for new life-saving treatments and cures to fruition, according to recommendations released today by three medical societies.

The numbers of infectious diseases trainees pursuing opportunities as physician researchers has steadily declined in recent years, even as needs for biomedical research to tackle emerging as well as established diseases continue, the Infectious Diseases Society of America, the HIV Medicine Association and the Pediatric Infectious Diseases Society note in Policy Recommendations for Optimizing the Infectious Diseases Physician-Scientist Workforce published in the Journal of Infectious Diseases today. Enumerating challenges facing physicians specializing in infectious diseases and filling the roles of both clinician and scientist, the authors of the article write that efforts to address attrition and bring new trainees into the field will require attention from federal, university, and professional entities.

Inadequate funding for fellowship opportunities as well as steep compensation disparities are among the factors driving the decline in numbers, according to the article - with median pay 20 percent less for infectious diseases researchers than for hospital or clinic employed infectious diseases physicians, and 27 percent less for those in private practice. In addition, structural barriers as well as implicit bias, leading to lower training completion and to significant pay disparities, also have limited entry into a field in which racial and gender diversity is critical, the authors write.

The authors recommend specific steps to increase both the number and quality of training opportunities, including expanded entry criteria for federal grant opportunities and collaborations between research and advocacy organizations.

NEW YORK, NY--August 14, 2018--Whether treatment for opioid abuse and dependence most commonly emphasized methadone administration, naltrexone injection, group psychotherapy or another procedure in 2017 depended on the state or region where the patient received care, according to a new white paper and state-by-state infographics from FAIR Health, a national, independent, nonprofit organization dedicated to bringing transparency to healthcare costs and health insurance information. Which procedures made up the largest share of total expenditures for opioid abuse and dependence also varied by region and state.

Analyzing 2017 data from its database of more than 26 billion privately billed healthcare claim records dating back to 2002, FAIR Health identified the top 10 procedure codes for specific treatments and services associated with opioid abuse and dependence diagnoses by utilization and aggregate cost in each US census region (Northeast, Midwest, South, West) and also reported the top 5 codes by utilization and aggregate cost in each state and the District of Columbia. Procedures include therapeutic procedures and other services, such as drug tests and visits to doctor's offices or emergency departments (EDs).

Among the regional differences the study revealed:

Methadone administration (H0020) was one of the 10 most common procedures by utilization in every region, but it was among the top 10 by cost in only one region, the Northeast.

Naltrexone injection (J2315) was in the top 10 list by cost in only one region, the Midwest.

Group psychotherapy (CPT® 90853) was one of the 10 most common procedures by utilization in every region except the South.

The top 10 procedures by utilization in the South included 7 drug tests or test-related procedures, more than in any other region.

The top 10 procedures by cost in the West included 6 therapeutic procedures, more than in any other region.

Two outpatient rehabilitative services were found in the top 10 lists by utilization or cost only in the South and West: intensive outpatient treatment (H0015) and partial hospitalization (S0201).

Two inpatient treatments, sub-acute detoxification (H0010) and short-term residential (H0018), were included among the top 10 procedures by cost in one region, the West.

ED visits were found in the top 10 lists by cost only in the Northeast and Midwest.

Across states, the study found these differences, among others:

Only New York had group counseling (H0005) as one of its five most common procedures by utilization and cost.

Only five states--Delaware, Nebraska, North Dakota, South Dakota and Wisconsin--included psychotherapy, 45 minutes (CPT 90834), as one of their five most common procedures by utilization.

Only California had intensive outpatient treatment in its top five list by utilization.

Sub-acute detoxification appeared in the top five lists of only two states, Mississippi and Tennessee, and there only by cost.

Only Wyoming included among its top five procedures by cost an ED visit, high severity, immediate significant threat to life or physiologic function (CPT 99285).

Dr. Martin A. Makary, Johns Hopkins Professor of Health Policy, said: "FAIR Health has issued an excellent study of an important aspect of the opioid crisis. Treatment of opioid abuse and dependence should be driven by science. This report represents a step in that direction."

FAIR Health President Robin Gelburd commented: "Our study unveils a tapestry of variation by region and state in the procedures most commonly associated with opioid abuse and dependence. The findings transform the states into living laboratories, offering opportunities to research the outcomes linked to the different treatment strategies."

This is the fourth in a series of white papers released by FAIR Health on the opioid epidemic. The first white paper examined national trends in the epidemic; the second, the impact of the epidemic on the healthcare system; and the third, geographic variations in the epidemic.

Aug. 13, 2018 - Medicare patients nationwide have low rates of preventive care visits - https://journals.lww.com/lww-medicalcare/Fulltext/2018/09000/Ethnoracial_Disparities_in_Medicare_Annual.5.aspx?PRID=MC_PR_081318" with the lowest rates found in older adults of minority race/ethnicity, reports a study in the September issue of Medical Care. The journal is published in the Lippincott portfolio by Wolters Kluwer.

Lower use of the Medicare Annual Wellness Visit (AWV) by non-white patients is partially explained by income and education - suggesting that the difference is related to factors associated with racial and ethnic inequality, according to the research by Kimberly E. Lind, PhD, MPH, and colleagues of the Colorado School of Public Health and the University of Colorado School of Medicine at the Anschutz Medical Campus in Aurora, Colo.

Dr. Lind comments, "While the Medicare AWV may help to reduce racial/ethnic health disparities, efforts will be needed to increase its use - not only by minority patients, but for the entire Medicare population. Education and income inequality by race and ethnicity have been a historical constant and remain a problem." Dr. Lind is now a research fellow at the Centre for Health Systems and Safety Research in the Australian Institute of Health Innovation at Macquarie University.

Factors Besides Race/Ethnicity Explain Variations in Medicare AWV Rates
The study included data on nearly 15,000 Medicare fee-for-service beneficiaries, aged 66 or older, participating in the nationally representative Medicare Current Beneficiary Survey from 2011 to 2013. Trends in use of the AWV were analyzed, including factors associated with higher or lower use of this preventive care visit. The study was the first to evaluate AWV utilization using self-reported race, ethnicity, income and education as opposed to Medicare administrative and claims data.

Introduced in 2011 as part of the Affordable Care Act, the AWV seeks to prevent disease and disability by increasing preventive services such as screening and vaccinations, based on the patient's current health and risk factors. The AWV is available once yearly, with no out-of-pocket costs to patients. (It is different from the "Welcome to Medicare" visit, which is only available in the first year of enrollment.)

"The absence of out-of-pocket payments makes the AWV a promising approach to increase utilization of preventive care," Dr. Lind and colleagues write. Because minority patients are more likely to have lower income and less likely to have supplemental insurance, the AWV might help to reduce racial/ethnic health disparities.

Throughout the study period, use of the AWV was low. In 2011, only 8.1 percent of Medicare beneficiaries used the AWV. In 2011 the rate was highest for white patients, 8.5 percent; and lowest in black patients, 4.5 percent. By 2013, the overall rate of AWV use increased to 13.4 percent. The greatest increase was seen in black patients, for who the rate of AWV use nearly tripled to 15.4 percent.

Overall, AWV use was lower in racial/ethnic minority groups (black, Hispanic, and "other race"), compared to white beneficiaries. After adjustment for income and education, racial/ethnic group was no longer a statistically significant factor. Dr. Lind comments, "This suggests that possible explanations of these differences are factors that are strongly associated with racial and ethnic differences, such as access to care, preferences for care, and knowledge of this relatively new benefit."

Use of the AWV was lower for beneficiaries living in rural area and higher for those who had a usual place for healthcare, other than the emergency room.

"Utilization of the AWV has increased modestly since its introduction, but remains low," Dr. Lind and colleagues conclude. "Our findings suggest the need to further promote the AWV among beneficiaries and providers...assuming that future research supports the effectiveness of the AWV in increasing preventive services and improving beneficiary health."

More than 100 years ago, German Nobel laureate Paul Ehrlich popularized the "magic bullet" concept -- a method that clinicians might one day use to target invading microbes without harming other parts of the body. Although chemotherapies have been highly useful as targeted treatments for cancer, unwanted side effects still plague patients. Now, researchers at the University of Missouri have demonstrated that specialized nucleic acid-based nanostructures could be used to target cancer cells while bypassing normal cells.

"Most of the therapeutic drugs are not able to discriminate the cancer cells from healthy cells," said David Porciani, a postdoctoral fellow in Donald Burke's lab at the MU Bond Life Sciences Center. "They are killing both cell populations (healthy and malignant), and the treatment can have harsher side effects than the cancer itself in the short term. We are developing 'smart' molecules that can bind with receptors that are found on the surface of cancer cells, thus representing a cancer signature. The idea is to use these smart molecules as vehicles to deliver chemotherapeutic drugs or diagnostics."

Using a molecular process that mimics a highly-accelerated form of natural evolution, Porciani and his team sought out nucleic acid ligands, or aptamers. Because of their three-dimensional structures, aptamers can be trained to bind to certain target molecules with high affinity and selectivity. When the target is a cancer-associated receptor, these aptamers can be used as molecular tools to recognize specifically diseased cells.

The team then "loaded" the aptamers with large, fluorescent RNAs generating nucleic-acid nanostructures. Upon incubation with target cancer and non-target cells, only malignant cells were illuminated by the nanostructure showing that the structures had correctly bonded with their intended targets.

"Next steps for our studies are to prove that these aptamers can be loaded with therapeutic molecules that specifically target and treat cancer cells leaving normal tissues untouched," Porciani said. "While aptamers have been proven in the past as tools to deliver small drugs, our method paves the way to deliver even larger and potentially more powerful RNA-based drugs possibly creating that 'magic bullet' that Erhlich described in the last century."

This research highlights the power of translational precision medicine and the promise of the proposed Translational Precision Medicine Complex at the University of Missouri. The TPMC will bring together industry partners, multiple schools and colleges on campus, and the federal and state government to enable precision and personalized medicine. Scientific advancements made at MU will be effectively translated into new drugs, devices and treatments that deliver customized patient care based on an individual's genes, environment and lifestyle, ultimately improving health and well-being of people.

Somewhere in the American Southwest or northern Mexico, there are probably the ruins of a scarlet macaw breeding operation dating to between 900 and 1200 C.E., according to a team of archaeologists who sequenced the mitochondrial DNA of bird remains found in the Chaco Canyon and Mimbres areas of New Mexico.

Remains of a thriving prehistoric avian culture and breeding colony of scarlet macaws exist at the northern Mexican site of Paquimé, or Casas Grande. However, this community existed from 1250 to 1450, well after the abandonment of Chaco Canyon, and could not have supplied these birds to Southwest communities prior to the 13th century, said Richard George, graduate student in anthropology, Penn State.

Historically, scarlet macaws lived from South America to eastern coastal Mexico and Guatemala, thousands of miles from the American Southwest. Previously, researchers thought that ancestral Puebloan people might have traveled to these natural breeding areas and brought birds back, but the logistics of transporting adolescent birds are difficult. None of the sites where these early macaw remains were found contained evidence of breeding -- eggshells, pens or perches.

"We were interested in the prehistoric scarlet macaw population history and the impacts of human direct management," said George. "Especially any evidence for directed breeding or changes in the genetic diversity that could co-occur with different trade networks."

The researchers sequenced the mitochondrial DNA of 20 scarlet macaw specimens, but were only able to obtain full sequences from 14. They then directly radiocarbon-dated all 14 birds with complete or near complete genomes and found they fell between 900 and 1200 CE.

"We looked at the full mitochondrial genome of over 16,000 base pairs to understand the maternal relationships represented in the Chaco Canyon and Mimbres regions," said George.

Mitochondrial DNA exists separate from the cell nucleus and is inherited directly from the mother. While nuclear DNA combines the DNA inherited from both parents, mitochondrial DNA can show direct lineage because all siblings have the same mtDNA as their mother, and she has the same mtDNA as her own siblings and mother, all the way back through their ancestry.

Scarlet macaws in Mexico and Central America have five haplogroups -- genetically similar, but not identical mitochondrial DNA lines -- and each haplogroup has a number of haplotypes containing identical DNA lines. The researchers found that their scarlet macaws were all from haplogroup 6 and that 71 percent of the birds shared one of four unique haplotypes. They report the results of this analysis today (Aug 13) in the Proceedings of the National Academy of Sciences.

The researchers found that the probability of obtaining 14 birds from the wild and having them all come from the same haplogroup, one that is small and isolated, was extremely small. A better explanation, especially because these specimens ranged over a 300-year period, is that all the birds came from the same breeding population and that this population existed somewhere in the American Southwest or northern Mexico.

"These birds all likely came from the same source, but we don't have any way to support that assumption without examining the full genome," said George. "However, the genetic results likely indicate some type of narrow breeding from a small founder population with little or no introgression or resupply."

However, no one has found macaw breeding evidence dating to the 900 to 1200 period in the American Southwest or northern Mexico.

"The next step will be to analyze macaws from other archaeological sites in Arizona and northern Mexico to narrow down the location of this early breeding colony," said Douglas Kennett, professor and head of anthropology, Penn State, and co-director or the project.

Tobacco content remains common on UK prime time TV, cropping up in a third of all programmes, despite advertising and broadcasting regulations designed to protect children from this kind of exposure, reveals research published online in the journal Tobacco Control.

The amount of exposure has hardly changed in five years, and is likely to heavily influence young people's take-up of smoking, say the researchers.

Tobacco content in film has been covered extensively, but relatively little attention has been paid to its inclusion on prime time TV, despite the fact that children are likely to spend more time watching TV than they are films, they point out.

The researchers therefore analysed the tobacco content of all programmes, adverts, and trailers broadcast on the five national free to air TV channels between 1800 and 2200 hours during the course of three separate weeks in September, October, and November 2015.

Their analysis included any actual or implied use, such as holding a cigarette without smoking it, or making a comment about smoking; smoking/tobacco paraphernalia; and presence of branding in 1 minute intervals. The results were then compared with those of a similar analysis carried out in 2010.

In all, 420 hours of broadcast footage, including 611 programmes, 909 adverts, and 211 trailers, were analysed.

Some 291 broadcasts (17% of all programmes) included tobacco content. The channel with the most tobacco content was Channel 5, and the one with the least was BBC2.

Tobacco content occurred in one in three TV programmes broadcast, and nearly one in 10 (8%) adverts or trailers.

Actual tobacco use occurred in one in eight (12%) programmes, while tobacco related content--primarily no smoking signs--occurred in just 2 percent of broadcasts. Implied use and branding were rare.

Although most tobacco content occurred after the 9 pm watershed, it still occurred on the most popular TV channels before then. And comparison with the previous analysis in 2010 showed that the number of 1 minute intervals containing any tobacco content increased, rising from 731 to 751 in 2015.

Tobacco advertising, promotion and sponsorship, including paid product placement in TV adverts, is banned in the UK, but tobacco imagery in TV programmes and trailers is exempt, and covered instead by media regulator, OfCom's, broadcasting code.

This code is designed to protect children by restricting depictions of tobacco use in children's programmes, and preventing the glamorisation of smoking in programmes broadcast before 9 pm.

"Audiovisual tobacco content remains common in prime-time UK television programmes and is likely to be a significant driver of smoking uptake in young people," emphasise the researchers.

"Guidelines on tobacco content need to be revised and more carefully enforced to protect children from exposure to tobacco imagery and the consequent risk of smoking initiation," they add.