Culture

While youth vaping rates have increased in recent years, most middle and high school students don't vape or smoke and very few vape or smoke daily, finds a study led by researchers at NYU School of Global Public Health.

The study, published this month in the journal Nicotine & Tobacco Research, finds that over 80 percent of youth do not use any tobacco and over 86 percent don't vape--and among the minority who do vape, most are not regular users. In addition, the study reveals that most youth who are vaping are also current or former smokers.

"Our findings underscore the importance of examining the full context of how youth are using vaping and tobacco products," said Allison Glasser, an assistant research scientist at NYU School of Global Public Health and the study's lead author. "The key to protecting youth in the United States is determining the patterns of frequency of use and co-use of vaping and tobacco products, which will give public health decision makers the best possible information to protect the public's health."

While the FDA and CDC's National Youth Tobacco Survey has shown a concerning increase in youth vaping in recent years, little is known about the frequency with which youth use e-cigarettes--if it's an occasional occurrence or a daily habit--as well as whether they also use more harmful smoked tobacco products like cigarettes and inexpensive cigars or cigarillos.

In this study, the researchers analyzed the 2018 National Youth Tobacco Survey in which more than 20,000 middle and high school students were asked about their use of various tobacco and vaping products in the past 30 days. The analysis was conducted on the 2018 survey, the latest available full data set; the 2019 National Youth Tobacco Survey, which showed that youth vaping continued to grow from 2018 to 2019, has not yet been made available for public analysis.

A critical finding across all surveys from 2013 to 2019 is that smoking actually decreased much more rapidly to a record low during the very same years vaping increased. From 2015 to 2018, daily cigarette smoking among youth declined from 1.2 percent to 0.9 percent, while regular vaping (20 or more out of the past 30 days) increased from 1.7 percent to 3.6 percent.

"The faster drop in smoking suggests vaping is helping displace youth use of much more deadly smoking--a net harm reduction benefit to the population as a whole," said David Abrams, a professor of social and behavioral sciences at NYU School of Global Public Health and a study coauthor.

The researchers also found that while youth vaping increased from 2017 to 2018, the increase was driven by infrequent e-cigarette use rather than regular use: in 2018, while 13.8 percent of students had vaped in the 30 days, more than half of them vaped five days or fewer.

Critically, the majority of youth vapers also use or have used more deadly tobacco products (60 to 88.9 percent, depending on the frequency of vaping). While there has been fear that e-cigarettes are introducing nicotine to many young people who otherwise would not have smoked, the data show otherwise--only a small proportion of tobacco-naïve youth report vaping.

"Examining tobacco and e-cigarette use patterns in youth is informative about the risk of continued use in adulthood. While in a perfect world young people would not be smoking or vaping, if the vast majority of youth who vape are already current or former smokers, vaping could offer them a safer alternative than cancer-causing cigarettes," said Ray Niaura, a professor of social and behavioral sciences at NYU School of Global Public Health and a study coauthor.

"This study provides us with a better understanding of youth vaping patterns, which is critical for creating effective public health policies around nicotine and tobacco. Reacting too quickly to reports of youth vaping without considering the full context could do more harm than good," added Abrams. "We need to avoid prohibitionist regulations like banning e-cigarettes--while leaving much more deadly cigarettes and cigars in corner stores--and instead should consider strong enforcement of age 21 sales restrictions. Prohibition creates a black market for vaping products or inadvertently pushes individuals back to smoking tobacco."

A cancer researcher at the University of Alberta has made a discovery that could unlock new ways to treat a rare blood disease.

By taking biopsies of skin lesions from patients suffering from cutaneous T-cell lymphoma, U of A dermatology researcher Robert Gniadecki discovered that the cancer cells found in the lesions on the skin originate from the blood, not the skin as was believed.

The protocol to treat the disease was to eliminate the cancer cells from the skin.

Based on his findings, Gniadecki believes it would be more effective to treat the malignant clones in the blood rather than waiting until the cells reach the skin and present as lesions.

He also noted that even when a patient has a barely noticeable lesion, there is already an abundance of cancer cells in the blood.

"They [the malignant clone cells in the blood] are less variable than the cells that grow in the skin, they are more immature, so it's easier to kill them," explained Gniadecki, who is the director of the Division of Dermatology and a member of the Cancer Research Institute of Northern Alberta.

Cutaneous T-cell lymphoma is a rare type of cancer that begins in T cells, which are part of the immune system. They develop mutations that cause them to attack skin cells causing lesions.

Gniadecki is also working with the Alberta Machine Intelligence Institute (Amii) to run the genetic information from his samples through a machine learning program to see whether there are any identifiable biomarkers in the blood that could suggest how the disease progresses.

"Those who have a horrible prognosis, we should treat them aggressively from day one," Gniadecki said.

Because cutaneous T-cell lymphoma is so rare--roughly 150 in the Edmonton area live with it--knowledge in the medical community about it is quite low and it's often not recognized early, said Gniadecki.

"The diagnostic delay can be up to five years until somebody actually makes the diagnosis; it's not psoriasis, it's not a bad infection of the skin, it's actually cancer growing in your skin," said Gniadecki. "It's progressive, and we have no cure for this. It's a huge medical need."

ITHACA, N.Y. - One wasp species has evolved the ability to recognize individual faces among their peers - something that most other insects cannot do - signaling an evolution in how they have learned to work together.

A team led by Cornell University researchers used population genomics to study the evolution of cognition in the Northern paper wasp, Polistes fuscatus. The research suggests the wasps' increasing intelligence provided an evolutionary advantage and sheds light on how intelligence evolves in general, which has implications for many other species - including humans.

"The really surprising conclusion here is that the most intense selection pressures in the recent history of these wasps has not been dealing with climate, catching food or parasites but getting better at dealing with each other," said Michael Sheehan, professor of neurobiology and behavior, and senior author on the paper. "That's pretty profound."

Many vertebrate animals can recognize individual faces, at least in some circumstances, but among insects, facial recognition is quite uncommon. This study explored how and when this ability evolved by analyzing patterns of genetic variations within species.

"It's kind of like 23andMe, but with paper wasps," Sheehan said.

The few species of insects that can recognize faces share one trait: communal societies with multiple queens. In communal groups with a single queen, like honeybee colonies, the roles are clear, and each individual knows its place. But paper wasps may have five or more queens in one nest and facial recognition helps these queens negotiate with one another.

While the research focused on paper wasps, the primary question Sheehan and his colleagues wanted to answer was how intelligence evolves in general.

"Our finding indicated that cognitive evolution is not necessarily incremental," Sheehan said. "There are mutations happening that cause big shifts. This suggests the possibility that rapid adaptation of cognitive ability could have been important in other species as well, like language in humans."

A protein naturally produced in the body has been found to suppress breast cancer metastasis in animal models of human tumors. Researchers led by Baylor College of Medicine also found that high levels of this protein, AKAP8, predicts a better survival for breast cancer patients.

The findings, in the current edition of the journal Nature Communications, show that AKAP8 inhibits metastasis by interfering with the production of proteins that promote metastatic behavior in cells, and suggest strategies that may help treat metastatic cancer in the future.

"Our laboratory investigates cellular mechanisms that regulate breast cancer metastasis. In a previous study we provided the first evidence that alternative splicing, a cellular process that enables cells to switch between different forms of the same protein, can functionally control tumor metastasis," said corresponding author Dr. Chonghui Cheng, associate professor at the Lester and Sue Smith Breast Center, of molecular and human genetics and of molecular and cellular biology at Baylor.

Alternative splicing is a natural cellular process that helps cells conduct many functions, such as wound healing and embryonic development. Through alternative splicing, cells can make a large number of proteins from a limited number of genes. It would be like putting together a number of different outfits by combining in different ways a limited number of pieces of clothing. In humans, around 95 percent of all genes are processed through alternative splicing. Just recently has this process also been shown to be involved in cancer.

In that pioneering study that brought alternative splicing to the field of cancer research, Cheng and her colleagues showed that of the two distinct forms of the protein CD44 that can be produced by alternative splicing, named CD44s and CD44v, only the former contributed to cancer cell survival. These findings have been confirmed by other reports about breast cancer and also other types of cancer.

In the current study, the researchers further investigated how alternative splicing contributes to cancer metastasis by looking for proteins that regulate alternative splicing events linked to metastasis.

AKAP8 helps keep cells in a non-metastatic state

Cheng and her colleagues screened cells looking for proteins functioning as alternative splicing modulators that prevented cells from becoming metastatic. They identified a set of proteins that were potentially key for tumor metastasis regulation and focused on AKAP8.

"We studied AKAP8 in metastatic breast cancer animal model systems of cancer cells from human patients," Cheng said. "We found that depletion of the AKAP8 protein in patient cancer cells promoted breast cancer metastasis in these mouse models. Furthermore, providing an external source of AKAP8 inhibited metastasis."

Taking it all together, the results support AKAP8 as an important regulator of alternative splicing events linked to tumor metastasis. It is not only able to predict metastatic breast cancer outcomes in patients, but also can inhibit metastatic breast cancer progression in animal models.

Cheng and her colleagues continued their investigations to determine how AKAP8 mediated its metastasis-suppressing effects. They discovered that, in addition to modulating alternative splicing of CD44, AKAP8 also regulated the alternative splicing of another protein called CLSTN1. In this case, of the two forms of CLSTN1, named CLSTN1S and CLSTN1L, AKAP8 tipped the balance toward the production of the former, which was associated with preventing cells from progressing toward a metastatic state. This was a previously unknown function of CLSTN1.

"We think that modulators of alternative splicing participate in a delicate balancing act of many different cellular proteins, such as CD44 and CLSTN1. Two types of modulators play a part in keeping the balance. One type, like AKAP8, modulates alternative splicing toward the production of proteins that help cells remain in a normal state. The other type tips the balance toward proteins that promote metastatic transformation," Cheng said. "If the balance is disturbed, tumor progression can be promoted. By investigating how the balance is kept and the factors that disturb the balance, we hope to understand a new layer of regulation of tumor metastasis and gain insights that could lead to treatments for metastatic cancer, a deadly disease."

Boston - Affecting more than 7 million adults in the United States, gout is characterized by a sudden onset of pain, swelling and stiffness in the joints and caused by the formation of urate crystal in small spaces between joints that builds up when high amounts of uric acid circulate in the blood. While gout is linked to consuming some foods, including red meat, seafood, and alcohol, it is also a common complication of blood pressure management and a frequently cited reason patients don't take their medication as directed. However, few studies provide guidance for physicians selecting antihypertensive medications for patients at risk for gout.

A new study led by physician-researchers at Beth Israel Deaconess Medical Center (BIDMC) reports that the antihypertensive drug amlodipine lowered long-term gout risk compared to two other drugs commonly prescribed to lower blood pressure. The findings are published in the Journal of Hypertension.

"Our study is clinically relevant as the prevalence of gout has been rising in the United States and the number of Americans meeting newly-revised diagnostic thresholds for hypertension has doubled," said corresponding author Stephen Juraschek, MD, PhD, Assistant Professor of Medicine at BIDMC. "Our study demonstrated that amlodipine was associated with a lower risk of gout compared with chlorthalidone or lisinopril, which has never been reported prior to this study."

Juraschek and colleagues conducted a secondary analysis of the data generated by the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). This clinical trial evaluated the effect of common blood pressure drugs on cardiovascular outcomes in more than 20,000 participants treated at 623 medical centers in North America between 1994 and 2002.

"Further research is needed to confirm these findings," said Juraschek. "Other health outcomes, such as heart failure, should also be considered with choosing a blood pressure drug."

A team led by researchers at Baylor College of Medicine found that not only do individual mammalian cells in a population fail to respond synchronously to estrogen stimulation, neither do individual gene copies, known as alleles. The findings, published in the recent edition of the journal Nucleic Acids Research, also showed that neither the level of estrogen receptor nor its activation status determined asynchronous cellular responses.

However, a small molecule inhibitor of selected estrogen coregulators increased the response of individual alleles to hormone, establishing a previously unrecognized mode of regulation of estro-gen-induced gene activation at the single cell level.

"Estrogen is a type of steroid hormone that modulates a large number of biological functions, both in males and females, by regulating the activity of hundreds of genes per cell," said first au-thor Dr. Fabio Stossi, associate professor of Molecular and Cellular Biology and technical direc-tor of the Integrated Microscopy Core at Baylor.

A great deal is known about how estrogen triggers its effects. It binds to a nuclear transcription factor (estrogen receptor, or ER), which in turn interacts with specific DNA sequences facilitating the recruitment of coregulators that participate in the regulation of gene expression. It was as-sumed that this process would likely happen simultaneously in all the ER-containing cells in a population that was stimulated with estrogen, but little was known of how actual single cells or individual copies of the same gene responded. Which is why researchers did not anticipate these finding at the single cell level.

Looking at individual cells and alleles

"In the current study, we worked with human breast cancer cell lines grown in the lab. Using both molecular and imaging analyses, we determined, at single cell and allele levels, the expres-sion of two well-characterized genes, GREB1 and MYC, whose activity is regulated by estro-gen," said corresponding author, Dr. Michael A. Mancini, professor of Molecular and Cellular Bi-ology, and Pharmacology and Chemical Biology at Baylor. Mancini is also the academic director of the long-running Integrated Microscopy Core (IMC) at Baylor and director of the recently-formed GCC Center for Advanced Microscopy and Image Informatics (CAMII), a CPRIT-funded resource across Baylor and the Texas A&M Institute for Bioscience and Technology.

The researchers incubated the cells in the lab and treated them with estrogen. Then they looked at the expression of GREB1 and MYC genes in individual cells, and at the expression of individ-ual alleles in each cell. As expected, they found that estrogen activated GREB1 and MYC genes quickly, within 15 minutes, but there was an unexpected and marked asynchronous response to hormone simulation at both the individual cell and allele levels.

"Our analyses showed that gene activation of cells in a population appeared more random than we expected. In single cells, the response of each copy of the gene was independent from that of its neighboring cells. In some cells, no alleles of the genes were active, whereas cells next to them would have some or all their gene copies active," Stossi said.

Nevertheless, the researchers explained, that although these findings had not been described before in estrogen receptor biology, they were not a complete surprise.

Studies in genetically identical bacteria have shown that, when subjected to the same treatment, not all the bacteria respond the same way. This is called phenotypical heterogeneity.

"We have been interrogating mechanisms of action of ER via state-of-the-art imaging/analysis since the 90's, with continual improvements in our resources as they are developed or when they come to market, but these recent studies have uncovered novel characteristics of estrogen ac-tion in mammalian cells for the first time," Mancini said. "Having phenotypical heterogeneity con-fers an important adaptation strategy to cell populations, whether they are cancerous or normal. If all the cells in a population responded the same way to a harmful stimulus, for instance, by stopping an essential function, then they would not have the capability of surviving. But respond-ing differently may allow some cells to survive."

What causes an asynchronous response?

The next experiments intended to determine what caused asynchronous estrogen-triggered gene activation. Since the imaging and image analysis routines that were developed and used were amenable to the fully automated, high throughput imaging/analysis platforms within the IMC and CAMII, we had a unique opportunity to explore this question.

First, the researchers hypothesized that cells responded differently to estrogen because the number of estrogen receptors per cell varied. They were surprised to find out that the number of the estrogen receptors expressed in cells was not strictly dictating whether a cell was going to activate the target genes. Then, the researchers investigated whether the cellular response to estrogen depended on the activation status of the estrogen receptor using a patient-linked, con-stitutively-active receptor, but again, they found no correlation.

Next, the researchers explored the possibility that estrogen receptor coregulators were involved in modulating the allele-by-allele response to estrogen. Utilizing the automated high throughput resources of the IMC/CAMII, they tested a collection of small molecule epigenetic inhibitors and identified one, called MS049, an inhibitor of two protein arginine methyltransferases, that mark-edly increased the expected number of active alleles per cell under estrogen stimulation, in a gene-specific manner.

"For the first time we were able to alter the nature of the estrogenic response at the allele level, indicating that there are pathways that serve as rheostats to maintain variability of response to a stimulus, thus preventing maximal and uniform behavior in a population of cells," Stossi said. "These findings suggested that modifying the activity of coregulators can tweak the variation of allele-by-allele hormonal responses in a gene-specific manner."

The findings provide novel insights into the complex nature of the regulation of gene expression in mammalian cells.

A 'Big Brother' data culture in rugby driven by performance management threatens to create heightened distrust, anxiety and insecurity among players, according to a new study.

The qualitative research, based on interviews with 10 players, coaches and analysts at an English Premiership club, suggests that data culture in the professional game can have unintended negative consequences on team morale.

Publishing their findings in the journal Organization, researchers from the University of Bath's Department for Health suggest performance metrics can play an important role in team management and coaching, but argue that teams must be mindful of their potential negative effects on players and on team morale.

For their study, interviewees told a story of how metrics and key performance indicators (KPIs) surrounded their every movement of their lives on and off the pitch. As a result, the researchers concluded, players increasingly focused on their own statistics rather than the performance of the team as a whole.

Against a backdrop where players were evaluated against KPIs covering factors such as their weight and diet, through to their performance on the pitch, including tackle rate in order to 'achieve optimal performances' some of the responses included:

"I can't do this because my stats might be wrong, might look wrong and why would I put myself in that position on a Monday morning because I can't win. That is exactly what it was, and players froze."

"You know we're not a financial institution, we're not run on numbers, we're people, we're emotional people."

"I say I don't have a problem with the amount of statistics, with the amount of monitoring they do with me, but it's the way they [the coaches] then deal with those statistics. I'm very much aware of how you can make statistics appear a certain way to certain people and manipulate them, so that's only where my concern comes in, where one minute it's positive but at whatever point they want to, because of the amount they have on you, they can turn either way, they can bend it wherever they want."

One particular concern for interviewees involved a notional score given to players: a so-called 'Work Efficiency Index', a number calculated based on multiple factors in the game. It was one example among others where players felt increasingly judged on numbers rather than their true performance.

The researchers stress that it is not necessarily the amount of data collected in training and in matches that is a concern, but rather how data is interpreted and communicated by clubs.

Dr Shaun Williams of the University of Bath's Department for Health explained: "The constant inhalation of numbers shackled the players' natural affinity and decision making, as they became subordinate to the metrics. Our study poses vital questions for those involved in high performance in terms of how linear and mechanical life can be made for employees or athletes. In this longitudinal study, we found fear and resentment both grew as players became too rational and risk averse in the constant presence of surveillance and monitoring."

Lead author Dr Andrew Manley, also of the Department for Health at the University of Bath, added: "Although the use of analytics can work to reveal hidden value and generate efficiencies, it is important that further research focuses on the restrictive consequences and emotive responses tied to a more encompassing form of worker control. Our study points to some of the unintended consequences that can occur as a result of such heavy data surveillance and the impact constant performance management has on the personal lives of those subjected to such organisational environments."

Since the 1900s, neuroscientists have known that the peripheral nervous systems of tetrapods (four-footed animals) vary greatly, but how these differences affect the way that animals walk, run, or move has not been well understood. Now, a study published in the Journal of Experimental Biology on January 27, authored by a New York Institute of Technology anatomy professor, suggests that neuromuscular adaptations in mammals and birds may have allowed them to become more nimble than reptiles and amphibians.

"This research could explain why tigers have a much smoother walk than crocodiles, which lumber and drag their abdomens, and perhaps one reason why today's humans have evolved to walk with such uniform steps," says lead author Michael Granatosky, Ph.D., assistant professor of Anatomy at New York Institute of Technology College of Osteopathic Medicine (NYITCOM).

Tetrapods have small receptors in their muscles called Golgi tendon organs, which protect muscles from forces during locomotion (walking) and other physical activity. When muscle tension becomes dangerous, these receptors signal the nervous system to produce reflexes that release tension and prevent injury. Amphibians and reptiles, which diverged from early tetrapods before mammals and birds, have freeform Golgi tendons located further from the muscle-tendon junction, suggesting that they detect stress across the entire muscle. In contrast, birds and mammals have encapsulated Golgi tendon organs set directly at the muscle-tendon junction, signifying an ability to detect tension in precise muscle areas, which would allow for more controlled motion. Now, researchers pose that birds and mammals owe their agile strides to these finely tuned receptors.

"These structural variations are well known, but no one has questioned what they actually mean for the animals," says Granatosky. "We studied the largest collection of zoological locomotive data to date, which spanned 30 years and 55 species, and found that these variations directly affect how animals respond to the forces acting on their limbs."

Continuing the work of his post-doctorate mentor Callum Ross, Ph.D., professor of Organismal Biology and Anatomy at the University of Chicago, Granatosky analyzed vast sets of data from zoos and research facilities in the U.S., Canada, and Germany. To survey bodyweight distribution in motion, animal steps were measured with a three-dimensional scale called a force plate. Reptile and amphibian strides were found to vary greatly with each step, but mammals and birds crossed the force plate with very consistent strides. The findings suggest that, while in motion, a predictable response to force provides a selective advantage that could conserve energy and allow birds and mammals to swiftly regain footing from a fall. Granatosky also believes that the less responsive nervous systems of reptiles and amphibians may have caused a need for protection that led the animals to adapt stronger bones.

"Reptile and amphibian bones can sustain forces ten times heavier than their weight, whereas bird and mammal bones can only sustain forces two and a half times their weight. It's possible that birds and mammals adapted lighter, more energy-efficient bone structures in response to no longer needing heavy, protective frames that demanded a great deal of energy," he says.

To test his theory, Granatosky will study whether Golgi tendon organs played an evolutionary role in bone density adaptation and energy expenditure. He is also collaborating with New York Institute of Technology engineering, architecture, and digital arts students to build robots that accurately simulate animal locomotion. The first robot will simulate the walking patterns of the blue-tongued skink, an Australian lizard commonly used as a model for early tetrapod locomotion.

Muscles need dystrophin in order to regenerate. Persons suffering from Duchenne muscular dystrophy lack this essential muscular protein due to mutations in the gene which is responsible for producing dystrophin. As a result, their existing muscle cells deteriorate over time and are gradually replaced by connective and fatty tissue; muscle strength weakens during the course of the disease. The first symptoms usually appear around the age of five. Children with the disease begin to have difficulties with movements they previously completed with ease, for example climbing stairs or getting up from the floor. At approximately the age of twelve, they are no longer able to walk, later losing movement in their arms and hands. Due to concomitant respiratory and cardiac failure, the majority of patients does not reach the age of 40. DMD affects mainly boys, since the responsible mutations are located in the dystrophin gene on the X chromosome.

Gene scissors remove defective gene sequence

An interdisciplinary Munich research team led by scientists from TUM has for the first time succeeded in correcting the mutated dystrophin gene in living pigs. In order to cut the defective gene sequence from the DNA of the animals' muscle and heart cells, the researchers modified the Crispr-Cas9 gene scissors. "These gene scissors are highly efficient and specifically corrected the dystrophin gene," says Prof. Wolfgang Wurst, developmental geneticist at TUM and the German Research Center for Environmental Health. It became then again possible to viably read the gene which had been unreadable because of the genetic defect, thus allowing for a successful protein biosynthesis. Now the shorter but stably formed dystrophin protein was able to improve muscle function. The animals treated were less susceptible to cardiac arrhythmia and had an increased life expectancy compared to animals with the disease that did not receive the therapy.

A permanent therapy

"Muscle and heart cells are long-lived cell structures. One half of all myocardial cells remain functional from birth throughout the entire lifecycle of a human being," says Prof. Christian Kupatt, cardiologist at university hospital TUM Klinikum rechts der Isar. "The genome of a cell is used for protein biosynthesis as long as the cell is alive, and once a cell has been affected by the therapy, it remains corrected. So if we change the genome of a myocardial cell, the correction is a long-term success, in contrast to the results of previous methods."

Therapeutic success with clinically relevant model

The gene sequence responsible for the dystrophin protein has already been successfully corrected in the past, however in mice and other animal models. "Our results are very promising, since for the first time, we have now been able to demonstrate therapeutic success in a clinically relevant large animal model," says Prof. Maggie Walter, neurologist at the LMU university hospital. In terms of important biochemical, clinical and pathological changes, the pig model mirrors Duchenne muscular dystrophy in humans. "Since the disease proceeds faster in our pig model, we were able to verify the efficacy of the therapeutic approaches within a manageable period of time," says Prof. Eckhard Wolf, LMU specialist in veterinary medicine.

A University of California, Berkeley, archaeologist has dug up ancient human feces, among other demographic clues, to challenge the narrative around the legendary demise of Cahokia, North America's most iconic pre-Columbian metropolis.

In its heyday in the 1100s, Cahokia -- located in what is now southern Illinois -- was the center for Mississippian culture and home to tens of thousands of Native Americans who farmed, fished, traded and built giant ritual mounds.

By the 1400s, Cahokia had been abandoned due to floods, droughts, resource scarcity and other drivers of depopulation. But contrary to romanticized notions of Cahokia's lost civilization, the exodus was short-lived, according to a new UC Berkeley study.

The study takes on the "myth of the vanishing Indian" that favors decline and disappearance over Native American resilience and persistence, said lead author A.J. White, a UC Berkeley doctoral student in anthropology.

"One would think the Cahokia region was a ghost town at the time of European contact, based on the archeological record," White said. "But we were able to piece together a Native American presence in the area that endured for centuries."

The findings, just published in the journal American Antiquity, make the case that a fresh wave of Native Americans repopulated the region in the 1500s and kept a steady presence there through the 1700s, when migrations, warfare, disease and environmental change led to a reduction in the local population.

White and fellow researchers at California State University, Long Beach, the University of Wisconsin-Madison and Northeastern University analyzed fossil pollen, the remnants of ancient feces, charcoal and other clues to reconstruct a post-Mississippian lifestyle.

Their evidence paints a picture of communities built around maize farming, bison hunting and possibly even controlled burning in the grasslands, which is consistent with the practices of a network of tribes known as the Illinois Confederation.

Unlike the Mississippians who were firmly rooted in the Cahokia metropolis, the Illinois Confederation tribe members roamed further afield, tending small farms and gardens, hunting game and breaking off into smaller groups when resources became scarce.

The linchpin holding together the evidence of their presence in the region were "fecal stanols" derived from human waste preserved deep in the sediment under Horseshoe Lake, Cahokia's main catchment area.

Fecal stanols are microscopic organic molecules produced in our gut when we digest food, especially meat. They are excreted in our feces and can be preserved in layers of sediment for hundreds, if not thousands, of years.

Because humans produce fecal stanols in far greater quantities than animals, their levels can be used to gauge major changes in a region's population.

To collect the evidence, White and colleagues paddled out into Horseshoe Lake, which is adjacent to Cahokia Mounds State Historical Site, and dug up core samples of mud some 10 feet below the lakebed. By measuring concentrations of fecal stanols, they were able to gauge population changes from the Mississippian period through European contact.

Fecal stanol data were also gauged in White's first study of Cahokia's Mississippian Period demographic changes, published last year in the Proceedings of the National Academy of Sciences journal. It found that climate change in the form of back-to-back floods and droughts played a key role in the exodus of Cahokia's Mississippian inhabitants.

But while many studies have focused on the reasons for Cahokia's decline, few have looked at the region following the exodus of Mississippians, whose culture is estimated to have spread through the Midwestern, Southeastern and Eastern United States from 700 A.D. to the 1500s.

White's latest study sought to fill those gaps in the Cahokia area's history.

"There's very little archaeological evidence for an indigenous population past Cahokia, but we were able to fill in the gaps through historical, climatic and ecological data, and the linchpin was the fecal stanol evidence," White said.

Overall, the results suggest that the Mississippian decline did not mark the end of a Native American presence in the Cahokia region, but rather reveal a complex series of migrations, warfare and ecological changes in the 1500s and 1600s, before Europeans arrived on the scene, White said.

"The story of Cahokia was a lot more complex than, 'Goodbye, Native Americans. Hello, Europeans,' and our study uses innovative and unusual evidence to show that," White said.

WASHINGTON (Jan. 27, 2020) -- The rate of recovery and a patient's length of stay at nursing and rehabilitation facilities are associated with a patient's mobility and their ability to provide self-care when they are discharged following hip fracture surgery, according to a new study from the George Washington University (GW), published in JAMA Network Open.

The authors of the study suggest that a care team should prioritize identifying a patient's recovery trajectory early enough in care to promote the best possible outcomes and allocate resources efficiently.

Medicare is shifting from payment for post-acute care services based on the volume provided to a payment system based on value as determined by patient characteristics and functional outcomes, placing responsibility on facilities to determine what a patient's care will entail. Nursing and rehabilitation facilities are responsible for ensuring that a patient's therapy time and length of stay match their needs. This formula of appropriate patient care matched with patient needs is critical to optimizing functional outcomes and manage costs of rehabilitation.

"This study is very timely," said Alison Cogan, PhD, OTR/L, adjunct assistant professor of health, human function, and rehabilitation sciences at the GW School of Medicine and Health Sciences (SMHS) and first author on the study. "There is a lot of pressure to be cost effective in clinical care across the board and maintain appropriate rehabilitation time for patients."

The researchers provided a retrospective analysis of data on patients from four inpatient rehabilitation facilities and seven skilled nursing facilities in the United States who received rehabilitation services for hip fracture and who had Medicare fee-for-service as their primary payer. The team categorized the patients into nine recovery groups based on low, medium, and high therapy minutes per day and low, medium, or high rate of functional gain per day. They measured the groups for functional mobility independence and self-care capabilities at the time each patient was discharged.

Cogan and the team found that rate of recovery and length of stay in skilled nursing and rehabilitation facilities were associated with mobility and self-care outcomes at discharge following hip fracture surgery. In particular, the authors found that for medium gain patients, being discharged from a facility in under 21 days may transfer additional the burden of care to family and caregivers, home health, and outpatient services, because these patients typically achieve functional independence at around 28 days in rehab.

"The inclination is typically to give a patient more therapy per day," said Trudy Mallinson, PhD, associate dean for health sciences research at SMHS, director of the Advanced Metrics Lab, where the study was produced, and senior author of the study. "But perhaps more isn't always the right thing to do. Maybe a longer stay is the right thing for some patients.

"This study is a first step. It's a way to start thinking about how we can help clinicians, patients, and caregivers think about what amount of therapy is appropriate for each patient's unique situation."

The next steps, according to the team, are to study with a larger national sample and also to apply the same methodology to other questions for patients with other conditions requiring rehabilitation services, such as stroke and joint replacement.

The rate of survival of very preterm babies in Canada increased 25% after the national Evidence-based Practice for Improving Quality (EPIQ) program was introduced in neonatal intensive care units (NICUs) across the country, according to new research in CMAJ (Canadian Medical Association Journal). http://www.cmaj.ca/lookup/doi/10.1503/cmaj.190940

The EPIQ program was introduced in 2003 by the Canadian Neonatal Network in 25 neonatal units to improve outcomes for premature babies. The study, originating from Sinai Health in Toronto, analyzed the effect of changes in care practices on outcomes for 50 831 infants born prematurely between 2004 and 2017. Researchers found that survival without major adverse health effects increased from 56.6% to 70.9% (25%) for very preterm babies and from 70.8% to 74.5% (5%) for babies born between 23 and 25 weeks' gestation, over the course of the 14-year program.

Preterm babies often have chronic health issues due to early premature birth, and this quality improvement program resulted in a significant reduction in several adverse outcomes for such babies. For example, the researchers also found that participation in the program was associated with a 15% decrease in bronchopulmonary dysplasia, a chronic lung disease associated with prematurity, and a 44% decrease in late-onset sepsis and other adverse conditions.

"Within the Canadian neonatal community, we have developed a system of continuously learning from each centre about how evidence-based strategies are implemented and what are the barriers and facilitators for improving quality," says Dr. Prakesh Shah, Paediatrician-in-Chief at Sinai Health and Director of the Canadian Neonatal Network. "This learning, combined with a regular flow of data to guide our practices, has significantly improved outcomes for most vulnerable newborns."

An international study of 10 high-income countries found that neonatal outcomes improved the most in Canada, perhaps because of the EPIQ program, which is now standard practice in Canadian NICUs. It has also been adapted in other countries.

"Our study shows that if we apply what we know in a systematic way, we can improve quality of care and outcomes over the longer term for preterm babies," says Dr. Shah.

In a related commentary, Dr. Mary Brindle, Cumming School of Medicine, University of Calgary, writes "EPIQ demonstrates a rare sustained achievement...which clearly illustrates the importance of commitment to ongoing improvement in national quality-improvement programs." She contrasts EPIQ with several other initiatives that have struggled to sustain change on a large scale. http://www.cmaj.ca/lookup/doi/10.1503/cmaj.200008

"Outcomes and care practices for preterm infants born at less than 33 weeks' gestation: a quality-improvement study" is published January 27, 2020

Higher income American households pay the most to finance the nation's health care system, but the burden of payments as a share of income is greatest among households with the lowest incomes, according to a new RAND Corporation study.

Households in the bottom fifth of income groups pay an average of 33.9% of their income toward health care, while families in the highest income group pay 16% of their income toward health care.

The analysis finds that households in the middle three income tiers pay between 19.8% and 23.2% of their income toward health care. The analysis considered all payments made by households to support health care, including taxes and employer contributions.

The study is published online by the journal Health Services Research.

"Our findings suggest that health care payments in the U.S. are even more regressive than suggested by earlier research," said Katherine G. Carman, lead author of the study and a senior economist at RAND, a nonprofit research organization. "As national discussions continue about health reform and health equity, it's important to understand how the current health care system distributes costs and payments."

In 2015, health care spending accounted for nearly 18 percent of the U.S.'s gross domestic product, a measure of the total value of goods produced and services provided by the nation. Ultimately all health care costs are paid by households, either in obvious ways such as through insurance premiums or out-of-pocket costs, in addition to less-visible ways such as employer-paid premiums and taxes.

RAND researchers analyzed a variety of sources of information to examine the burden that different families face to pay for health care, as well as the relationship between who pays for care and who receives care.

Researchers combined data from multiple sources collected in 2015, including the Survey of Income and Program Participation, the Medical Expenditure Panel Survey, the Kaiser Family Foundation/Health Research Education Trust Employer Health Benefits Survey, the American Community Survey and the National Health Expenditure Accounts.

Previous research has examined the distribution of health care financing, but the new RAND study considers payments made to finance health care, the dollar value of benefits received, and the impact on different groups by age, source of insurance and size of income.

The RAND study also is the first to consider the burden of health costs among people who are in nursing homes and other institutions, a calculation that led to higher estimates of health spending. The burden is particularly large on low-income people who need long-term care because in order to qualify for public benefits they must first spend most of their savings.

"We think this is a particularly important addition because those in nursing homes are among the most vulnerable in terms not only of their health, but also of the large financial burden that they face," Carman said.

While out-of-pocket spending, including insurance premiums, is the most obvious payment most people make for health care, the RAND study found it accounted for just 9.1% of health care costs. The vast bulk of health care costs are paid through health insurance premiums and taxes.

The study found that payments to finance health care was $9,393 per person, or 18.7% of average household income.

Examining benefits by type of insurance, researchers found that Americans with Medicare receive the greatest dollar value of health care, a result of older people generally using more health care services.

Those with Medicaid have the largest dollar value of health care received as a percent of income, which corresponds to the lower income and generally poorer health among the group. People with employer-sponsored insurance received the lowest dollar value of health care.

Unsurprisingly, those with lower income are much more likely to benefit from redistribution of health care payments made by others toward health care services.

The study found that households in the three lowest income groups receive more health care services than they pay for through all forms of payments. In the fourth income group, payments and the dollar value of care received are similar.

Households in the highest of the five income groups are paying much more into the system than they receive in health care services.

"Understanding how different groups contribute to and and benefit from health care spending is difficult for researchers, policymakers and the general public," Carman said. "This work provides better insight into how the American health care system redistributes contributions and spending across different parts of society."

At a glance:

Research using heart cells from squirrels, mice and people identifies an evolutionary mechanism critical for heart muscle function.

Gene defect that affects a protein found in the heart muscle interferes with this mechanism to cause hypertrophic cardiomyopathy, a potentially fatal heart condition.

Imbalance in the ratio of active and inactive protein disrupts heart muscle's ability to contract and relax normally, interferes with heart muscle's energy consumption.

Treatment with a small-molecule drug restores proper contraction, energy consumption in human and rodent heart cells.

If affirmed in subsequent studies, the results can inform therapies that could halt disease progression, help prevent common complications, including arrhythmias and heart failure.

The heart's ability to beat normally over a lifetime is predicated on the synchronized work of proteins embedded in the cells of the heart muscle.

Like a fleet of molecular motors that get turned on and off, these proteins cause the heart cells to contract, then force them to relax, beat after life-sustaining beat.

Now a study led by researchers at Harvard Medical School, Brigham and Women's Hospital and the University of Oxford shows that when too many of the heart's molecular motor units get switched on and too few remain off, the heart muscle begins to contract excessively and fails to relax normally, leading to its gradual overexertion, thickening and failure.

Results of the work, published Jan. 27 in Circulation, reveal that this balancing act is an evolutionary mechanism conserved across species to regulate heart muscle contraction by controlling the activity of a protein called myosin, the main contractile protein of the heart muscle.

The findings--based on experiments with human, mouse and squirrel heart cells--also demonstrate that when this mechanism goes awry it sets off a molecular cascade that leads to cardiac muscle over-exertion and culminates in the development of hypertrophic cardiomyopathy (HCM), the most common genetic disease of the heart and a leading cause of sudden cardiac death in young people and athletes.

"Our findings offer a unifying explanation for the heart muscle pathology seen in hypertrophic cardiomyopathy that leads to heart muscle dysfunction and, eventually, causes the most common clinical manifestations of the condition," said senior author Christine Seidman, professor of genetics in the Blavatnik Institute at Harvard Medical School, a cardiologist at Brigham and Women's Hospital and a Howard Hughes Medical Institute Investigator.

Importantly, the experiments showed that treatment with an experimental small-molecule drug restored the balance of myosin arrangements and normalized the contraction and relaxation of both human and mouse cardiac cells that carried the two most common gene mutations responsible for nearly half of all HCM cases worldwide.

If confirmed in further experiments, the results can inform the design of therapies that halt disease progression and prevent complications.

"Correcting the underlying molecular defect and normalizing the function of heart muscle cells could transform treatment options, which are currently limited to alleviating symptoms and preventing worst-case scenarios such as life-threatening rhythm disturbances and heart failure," said study first author Christopher Toepfer, who performed the work as a postdoctoral researcher in Seidman's lab and is now a joint fellow in the Radcliffe Department of Medicine at the University of Oxford.

Some of the current therapies used for HCM include medications to relieve symptoms, surgery to shave the enlarged heart muscle or the implantation of cardioverter defibrillators that shock the heart back into rhythm if its electrical activity ceases or goes haywire. None of these therapies address the underlying cause of the disease.

Imbalance in the motor fleet

Myosin initiates contraction by cross-linking with other proteins to propel the cell into motion. In the current study, the researchers traced the epicenter of mischief down to an imbalance in the ratio of myosin molecule arrangements inside heart cells. Cells containing HCM mutations had too many molecules ready to spring into action and too few myosin molecules idling standby, resulting in stronger contractions and poor relaxation of the cells.

An earlier study by the same team found that under normal conditions, the ratio between "on" and "off" myosin molecules in mouse heart cells is around 2-to-3. However, the new study shows that this ratio is off balance in heart cells that harbor HCM mutations, with disproportionately more molecules in active versus inactive states.

In an initial set of experiments, the investigators analyzed heart cells obtained from a breed of hibernating squirrel as a model to reflect extremes in physiologic demands during normal activity and hibernation. Cells obtained from squirrels in hibernation--when their heart rate slows down to about six beats per minute--contained 10 percent more "off" myosin molecules than the heart cells of active squirrels, whose heart rate averages 340 beats per minute.

"We believe this is one example of nature's elegant way of conserving cardiac muscle energy in mammals during dormancy and periods of deficient resources," Toepfer said.

Next, researchers looked at cardiac muscle cells from mice harboring the two most common gene defects seen in HCM. As expected, these cells had altered ratios of "on" and "off" myosin reserves. The researchers also analyzed myosin ratios in two types of human heart cells: Stem cell-derived human heart cells engineered in the lab to carry HCM mutations and cells obtained from the excised cardiac muscle tissue of patients with HCM. Both had out-of-balance ratios in their active and inactive myosin molecules.

Further experiments showed that this imbalance perturbed the cells' normal contraction and relaxation cycle. Cells harboring HCM mutations contained too many "on" myosin molecules and contracted more forcefully but relaxed poorly. In the process, the study showed, these cells gobbled up excessive amounts of ATP, the cellular fuel that sustains the work of each cell in our body. And because oxygen is necessary for ATP production, the mutated cells also devoured more oxygen than normal cells, the study showed. To sustain their energy demands, these cells turned to breaking down sugar molecules and fatty acids, which is a sign of altered metabolism, the researchers said.

"Taken together, our findings map out the molecular mechanisms that give rise to the cardinal features of the disease," Seidman said. "They can help explain how chronically overexerted heart cells with high energy consumption in a state of metabolic stress can, over time, lead to a thickened heart muscle that contracts and relaxes abnormally and eventually becomes prone to arrhythmias, dysfunction and failure."

Restoring balance

Treating both mouse and human heart cells with an experimental small-molecule drug restored the myosin ratios to levels comparable to those in heart cells free of HCM mutations. The treatment also normalized contraction and relaxation of the cells and lowered oxygen consumption to normal levels.

The drug, currently in human trials, restored myosin ratios even in tissue obtained from the hearts of patients with HCM. The compound is being developed by a biotech company; two of the company's co-founders are authors on the study. The company provided research support for the study.

In a final step, the researchers looked at patient outcomes obtained from a database containing medical information and clinical histories of people diagnosed with HCM caused by various gene mutations. Comparing their molecular findings from the laboratory against patient outcomes, the scientists observed that the presence of genetic variants that distorted myosin ratios in heart cells also predicted the severity of symptoms and likelihood of poor outcomes, such as arrhythmias and heart failure, among the subset of people that carried these very genetic variants.

What this means, the researchers said, is that clinicians who identify patients harboring gene variants that disrupt normal myosin arrangements in their heart muscle could better predict these patients' risk of adverse clinical course.

"This information can help physicians stratify risk and tailor follow-ups and treatment accordingly," Seidman said.

Among men with prostate cancer who received care from the Veterans Affairs (VA) Health System, an equal-access health care system, African American men did not have more advanced disease at the time of diagnosis or die earlier than white men, unlike trends seen in the greater U.S. population of patients with prostate cancer. The findings are published early online in CANCER, a peer-reviewed journal of the American Cancer Society.

African American men in the general U.S. population are more than twice as likely to die from prostate cancer as non-Hispanic white men. To examine whether access to health care may play a role in this disparity, a team led by Brent Rose, MD, of the University of California San Diego School of Medicine and the VA San Diego Healthcare System, analyzed information on more than 20 million veterans who receive care through the VA Health System. The analysis included 60,035 men diagnosed with prostate cancer between 2000 and 2015: 30.3 percent were African American and 69.7 percent were non-Hispanic white.

The researchers found that African American men were not more likely to experience delays in diagnosis and care. Also, African American men were not more likely to present with more advanced disease. Finally, African American men were not more likely to die from their disease. These outcomes for African American men were seen even though they were more likely to live in lower-income areas.

The findings indicate that African American men who receive equitable screening and treatment can expect to have relatively similar outcomes as white men. Access to high-quality medical care may help address some of the racial disparities seen among men diagnosed with the disease.

"These results suggest that poorer outcomes for African American men with prostate cancer may not be a foregone conclusion. With smart public policy choices, we may be able to reduce or even eliminate disparities and achieve equal outcomes for all men with prostate cancer," said Dr. Rose.