Culture

A new study from the Regenerative Bioscience Center at the University of Georgia is the first to suggest that COVID-19 does not directly damage taste bud cells.

Contrary to previous studies that have shown damage may be caused directly by the virus particle, the researchers, led by Hongxiang Liu, associate professor of animal and dairy science in UGA's College of Agricultural and Environmental Sciences, found that taste loss is likely caused indirectly by events induced during COVID-19 inflammation.

An increasing number of COVID-19 patients have reported losses of smell and/or taste, prompting the CDC to add it to the growing list of symptoms for COVID-19. Recent research shows 20%-25% of patients now report a loss of taste.

"More alarming is the rate of patients reporting loss of taste at a later date, sometime after exposure to the virus," said Liu. "This is something we need to keep a careful eye on."

Published in ACS Pharmacology & Translational Science, the study further indicates that taste bud cells are not vulnerable to SARS-CoV-2 infection, because most of them do not express ACE2, a gateway that the virus uses to enter the body.

"This study isn't the first to study ACE2 expression in the oral cavity," said Liu. "But it is the first to show, specifically in relation to coronavirus and taste bud cell survival, that there are likely other cell death mechanisms at play."

Liu and her colleagues wanted to find out whether ACE2 was expressed specifically in taste bud cells, as well as when this receptor first emerges on oral tissue cells during fetal development, by studying mice as a model organism.

Although the mouse version of ACE2 isn't susceptible to SARS-CoV-2, studying where it's expressed in mice could still help clarify what's happening when people become infected and lose the sense of taste, given that mouse and human share similar expression patterns of genes.

"Mice have a different cellular copy of ACE2, making them impervious to SARS-CoV-2 infection," said Liu. "A logical first step was to genetically engineer a model to examine the ACE2 receptor expression in wild type mice, to provide insights into what happens in people."

By analyzing data from oral cells of adult mice, the researchers found that ACE2 was enriched in cells that give the tongue its rough surface, but couldn't be found in most taste bud cells. That means the virus probably does not affect taste loss through direct infection of these cells.

"It's clear from the data, that future designs of therapeutics directed at ACE2 receptors would likely not be as effective in treating taste loss of patients suffering from COVID-19," said Liu.

According to the team, more researchers have jumped into studying coronavirus and have published more data for smell loss than taste.

"Anosmia coronavirus research is being published at a faster pace," said Liu. "This is the only COVID-19 research that we know of, that involves the mechanisms of taste loss. Taste loss in the tongue is more complex and harder to validate, because of the complexity of cells, tissue structures, and the limited expression level of the ACE2 receptor."

Biological sex is typically understood in binary terms: male and female. However, there are many examples of animals that are able to modify sex-typical biological and behavioral features and even change sex. A new study, which appears in the journal Current Biology, identifies a genetic switch in brain cells that can toggle between sex-specific states when necessary, findings that question the idea of sex as a fixed property.

The research-- led by Douglas Portman, Ph.D., an associate professor in the University of Rochester Department of Biomedical Genetics and the Del Monte Institute for Neuroscience -was conducted in C. elegans, a microscopic roundworm that has been used in labs for decades to understand the nervous system. Many of the discoveries made using C. elegans apply throughout the animal kingdom and this research has led to a broader understanding of human biology. C. elegans is the only animal whose nervous system has been completely mapped, providing a wiring diagram - or connectome - that is helping researchers understand how brain circuits integrate information, make decisions, and control behavior.

There are two sexes of C. elegans, males and hermaphrodites. Though the hermaphrodites are able to self-fertilize, they are also mating partners for males, and are considered to be modified females. A single gene, TRA-1, determines the sex of these roundworms. If a developing worm has two X chromosomes, this gene is activated and the worm will develop into a female. If there is only one X chromosome, TRA-1 is inactivated, causing the worm to become a male.

The new study shows that the TRA-1 gene doesn't go completely silent in males, as had been previously thought. Instead, it can go into action when circumstances compel males to act more like females. Typically, C. elegans males prefer searching for mates over eating, in part because they can't smell food as well as females do. But if a male goes too long without eating, it will dial up its ability to detect food and acts more like a female. The new research shows that TRA-1 is necessary for this switch, and without it hungry males can't enhance their sense of smell and stay locked in the default, food-insensitive mate-searching mode. TRA-1 does the same job in juvenile males - it activates efficient food detection in males that are too young to search for mates.

"These findings indicate that, at the molecular level, sex isn't binary or static, but rather dynamic and flexible," said Portman. "The new results suggest that aspects of the male nervous system might transiently take on a female 'state,' allowing male behavior to be flexible according to internal and external conditions."

A separate study appearing Current Biology by a team of collaborating researchers at Columbia University further describes the complex molecular mechanism by which TRA-1 is controlled by sex chromosomes and other cues.

University of Toronto Engineering researchers have discovered a dose threshold that greatly increases the delivery of cancer-fighting drugs into a tumour.

Determining this threshold provides a potentially universal method for gauging nanoparticle dosage and could help advance a new generation of cancer therapy, imaging and diagnostics.

"It's a very simple solution, adjusting the dosage, but the results are very powerful," says MD/PhD candidate Ben Ouyang, who led the research under the supervision of Professor Warren Chan.

Their findings were published today in Nature Materials, providing solutions to a drug-delivery problem previously raised by Chan and researchers four years ago in Nature Reviews Materials.

Nanotechnology carriers are used to deliver drugs to cancer sites, which in turn can help a patient's response to treatment and reduce adverse side effects, such as hair loss and vomiting. However, in practice, few injected particles reach the tumour site.

In the Nature Reviews Materials paper, the team surveyed literature from the past decade and found that on median, only 0.7 percent of the chemotherapeutic nanoparticles make it into a targeted tumour.

"The promise of emerging therapeutics is dependent upon our ability to deliver them to the target site," explains Chan. "We have discovered a new principle of enhancing the delivery process. This could be important for nanotechnology, genome editors, immunotherapy, and other technologies."

Chan's team saw the liver, which filters the blood, as the biggest barrier to nanoparticle drug delivery. They hypothesized that the liver would have an uptake rate threshold -- in other words, once the organ becomes saturated with nanoparticles, it wouldn't be able to keep up with higher doses. Their solution was to manipulate the dose to overwhelm the organ's filtering Kupffer cells, which line the liver channels.

The researchers discovered that injecting a baseline of 1 trillion nanoparticles in mice, in vivo, was enough to overwhelm the cells so that they couldn't take up particles quick enough to keep up with the increased doses. The result is a 12 percent delivery efficiency to the tumour.

"There's still lots of work to do to increase the 12 percent but it's a big step from 0.7," says Ouyang. The researchers also extensively tested whether overwhelming Kupffer cells led to any risk of toxicity in the liver, heart or blood.

"We tested gold, silica, and liposomes," says Ouyang. "In all of our studies, no matter how high we pushed the dosage, we never saw any signs of toxicity."

The team used this threshold principle to improve the effectiveness of a clinically used and chemotherapy-loaded nanoparticle called Caelyx. Their strategy shrank tumours 60 percent more when compared to Caelyx on its own at a set dose of the chemotherapy drug, doxorubicin.

Because the researchers' solution is a simple one, they hope to see the threshold having positive implications in even current nanoparticle-dosing conventions for human clinical trials. They calculate that the human threshold would be about 1.5 quadrillion nanoparticles.

"There's a simplicity to this method and reveals that we don't have to redesign the nanoparticles to improve delivery," says Chan. "This could overcome a major delivery problem."

Injuries induce the initiation of inflammation to control the damage. However, the resolution of the injury-induced inflammation leading to healing is not well characterized. This new article by researchers at the Inflammation Research Foundation suggests that the resolution process is under significant dietary control and thus can be optimized by using a highly defined systems-based nutritional approach.

In particular, a successful resolution of injury-induced inflammation requires the continuous balance of hormonal and genetic factors. The essential hormones involved in the process are eicosanoids derived from omega-6 fatty acids that need to be balanced by resolvins derived from omega-3 fatty acids. Likewise, the gene transcription factor NF-κB that controls inflammation must be offset by the activation of AMPK, which is the genetic master switch of metabolism and repair of damaged tissue.

"This balancing act of initiation of inflammation and its ultimate resolution that leads to healing is a systems-based approach," states Dr. Barry Sears, the President of the Inflammation Research Foundation. "The activation of resolution requires a sequential orchestration of reducing, resolving, and repairing of the injury-induced inflammation. Each step of the process can be either enhanced or inhibited by the diet."

The article outlines an appropriate calorie-restricted anti-inflammatory diet that is needed to reduce inflammation, the levels of omega-3 fatty acids required to resolve inflammation, and the levels of dietary polyphenols required to activate AMPK to repair the tissue damage caused by the inflammation. Furthermore, the appropriate blood markers to indicate success in optimizing each distinct phase of resolution are discussed in the article.

Since injuries are at random, the mechanisms and dietary constraints required for their successful orchestration leading to healing must be continually optimized. If not, then unresolved inflammation may become permanent in the form of either fibrosis or the development of senescence cells leading to earlier onset of chronic disease and acceleration of the aging process.

A group of scientists from Skoltech and the Institute for Information Transmission Problems of RAS (IITP RAS) showed, using Lake Baikal amphipods as an example, that parallel evolution driven by adaptations can be detected at the whole-genome level. The research was published in the Genome Biology and Evolution journal.

Similar adaptations are sometimes known to result from exactly the same mutations that occurred independently. The phenomenon is commonly termed "parallel evolution" to describe evolution that keeps repeating itself. It is usually hard to prove that such "parallel" mutations did not occur by pure accident but actually help organisms to adapt to their environment. Thus far, adaptive parallel mutations have been found in some individual genes or small groups of interrelated genes only.

A team of Skoltech and IITP RAS researchers led by Georgii Bazykin, an evolutionary biologist and a professor at Skoltech, undertook extensive bioinformatics analysis of protein-coding sequences of 46 amphipod species from Lake Baikal. The scientists were eager to see whether closely related amphipods from a Baikalian species flock displayed an elevated rate of adaptive parallel evolution.

The research suggests that adaptive parallel mutations are more common than random parallel mutations in protein-coding sequences of Lake Baikal amphipods and actually affect several thousand genes. Drawing on the basic laws of molecular evolution, the scientists showed that the mutations they discovered were indeed caused by the species' need to adapt to the environment. However, the exact adaptations behind parallel evolution still remain a mystery.

"Lake Baikal is home to hundreds of species of endemic amphipods that evolved from several species in their distant ancestry and embrace a variety of ecological niches from predators to planktonic forms and parasites. Parallels were found even between forms with totally different lifestyles," says Valentina Burskaia, the first author of the study and a Skoltech PhD student.

Coronaviruses were detected in a high proportion of bats and rodents in Viet Nam from 2013 to 2014, with an increasing proportion of positive samples found along the wildlife supply chain from traders to large markets to restaurants, according to a study published August 10 in the open-access journal PLOS ONE by Amanda Fine of the Wildlife Conservation Society and colleagues. As noted by the authors, the amplification of coronaviruses along the wildlife supply chain suggests maximal risk for end consumers and likely explains the coronavirus spillover to people.

Outbreaks of emerging coronaviruses in the past two decades and the current pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlight the importance of this viral family as a public health threat. Human-wildlife contact with a bat or an intermediate host species in China almost certainly triggered a coronavirus spillover event that may have involved wildlife markets and led to the pandemic spread of SARS-CoV-2, according to the latest scientific evidence. Beyond China, commercial wildlife farming in Viet Nam is part of the expanded international wildlife trade that is thought to contribute to global epidemics, such as SARS and now coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2.

To better understand the natural hosts of coronaviruses and the risk for these wildlife-human interfaces to facilitate spillover into humans, Fine and her collaborators investigated presence of viruses in the coronavirus family and diversity in wildlife at wildlife-human interfaces in Viet Nam from 2013 to 2014 (years prior to the emergence of SARS-CoV-2).

They observed high proportions of positive samples of coronaviruses among field rats (34.0%, 239/702) destined for human consumption and bats in guano farms (74.8%, 234/313) adjacent to human dwellings. The odds of coronavirus detection increased along the supply chain, from field rats sold by traders (20.7%, 39/188), to field rats sold in large markets (32.0%, 116/363), and field rats served in restaurants (55.6%, 84/151). Coronaviruses were also detected in rodents on most wildlife farms sampled (60.7%, 17/28), affecting Malayan porcupines (6.0%, 20/331) and bamboo rats (6.3%, 6/96) raised for human consumption. To minimize the public health risks of viral disease emergence, the authors recommend improving coronavirus surveillance in wildlife and implementing targeted wildlife trade reform.

The authors add: "This study shows the wildlife supply chain generates a one-two punch when it comes to spillover risk. It is known to increase contact rates between wildlife and people and here we show how it greatly amplifies the number of infected animals along the way."

As the world continues to closely monitor the newest coronavirus outbreak, the government of South Korea has been able to keep the disease under control without paralyzing the national health and economic systems. In a new research article published in The American Review of Public Administration, University of Colorado Denver researcher Jongeun You reviewed South Korea's public health policy to learn how the country managed coronavirus from January through April 2020.

Testing Timeline

In January, the Korea Centers for Disease Control and Prevention, in partnership with the Korean Society for Laboratory Medicine and the Korean Association of External Quality Assessment Service, developed and evaluated the real-time reverse transcription polymerase chain reaction (rRT-PCR) diagnostic method for coronavirus.

By February, the diagnostic kit was authorized, and as of March 9, 15,971 kits were produced, capable of testing 522,700 people.

As of April 15, South Korea has tested 534,552 people for coronavirus, which is 10.4 people per one thousand population. South Korea also operated 600 screening centers (including 71 drive-through centers), and more than 90 medical institutions assessed specimens with an rRT-PCR test.

According to You's research, the critical factors in South Korea's public health administration and management that led to success include national infectious disease plans, collaboration with the private sector, stringent contact tracing, an adaptive health care system, and government-driven communication. The South Korean government proactively found patients who contracted coronavirus, disclosed epidemiologic findings of confirmed patients to the public, and provided differentiated treatments based on the severity of symptoms. Unlike other major nations, South Korea has a mostly homogenous cultural and institutional structure, which enabled the policies put in place by the government to become effective.

This chart demonstrates how South Korea was able to limit the number of coronavirus deaths compared to other major countries around the world.

This chart demonstrates how South Korea was able to limit the number of coronavirus deaths compared to other major countries around the world.

The Three Major Keys to South Korea's Success

South Korea conducted rigorous and extensive epidemiologic field investigations for coronavirus cases. This process included interviews with patients and triangulation of multiple sources of information (e.g., medical records, credit card and GPS data). The Institute for Future Government's survey in 2020 found that 84% of South Koreans accept the loss of privacy as a necessary tradeoff for public health security.

South Korea is a democratic unitary political system. The local governments have limited autonomy and its public health governance is centralized, enabling South Korean agencies to act quickly to implement policy decisions at the local level. After the MERS outbreak in 2015, the South Korean government expanded legal and administrative boundaries regarding pandemic responses, enabling public administration to acknowledge the different procedures. For example, the Infectious Disease Control and Prevention Act was amended significantly to prevent infectious disease and secure the public's right to know through surveillance and tracing techniques.

Lastly, the public health budget and flexible fiscal management systems allowed the South Korean government to provide adequate resources. The South Korean government and national health insurance program shouldered the full cost of coronavirus testing, quarantine, and treatment for Korean citizens and noncitizens. Furthermore, on March 17, 2020, the South Korean Legislature passed the supplementary budget of 11.7 trillion KRW ($10.1 billion) in 12 days. The Korean Ministry of Health and Welfare's (KMHW) supplementary budget passed in March 2020 is 3.7 trillion KRW ($3.2 billion), which enabled the KMHW to increase COVID-19 prevention and treatment facilities and to support medical institutions and workers.

United States Viability

"There are many variables to consider when emulating policies from other countries," said Jongeun You. "South Korea's extensive surveillance and contact tracing using ICT (information and communications technology) may not be applicable at the federal level in the U.S. due to different cultural norms."

According to You, what the United States could have adopted from South Korea was its ability to quickly ramp up its testing capacity. As mentioned above, South Korea had testing capabilities by end of January after a fast review from the Korean FDA. In the United States, on February 12, 2020, when public and private labs had not yet received FDA approval for their own tests, the CDC revealed that a CDC-designed test kit contained a faulty reagent.

Public Administrator Implications

You suggests the public administrators need to meticulously document everything--and in a timely manner. Using this information, administrators must go one step further and update policy regarding key lessons learned.

"Though many solutions are emerging, I believe one essential solution for public administrators is to collect documentation about their successes and struggles, and what they hear from citizens and residents about policy implementation and communication."

Reducing the amount of protein in the urine of patients with focal segmental glomerulosclerosis (FSGS), a rare disease in which scar tissue forms on the parts of the kidneys that filter waste from the blood, can significantly slow declines in kidney function and extend time before patients' kidneys fail, a new analysis by a Children's National Hospital researcher and her colleagues shows. These findings, published online Aug. 10, 2020, in the American Journal of Kidney Disease, could provide hope for patients who are able to lower their urinary protein with available treatments but aren't able to achieve complete remission, the researchers say.

FSGS affects about seven per every million people in the general population. However, in the United States, it's responsible for between 5 and 20% of all cases of end stage kidney disease (ESKD), a condition in which the kidney function declines enough that patients can't survive without dialysis or a kidney transplant. There are no proven treatments specifically targeting FSGS, but steroids and other immunosuppressants have shown promise in clinical trials.

One characteristic sign of FSGS is proteinuria, in which too much protein is present in patients' urine. Most clinical trials of FSGS treatments have focused on complete remission of proteinuria as a sign that the intervention is working. However, says Marva Moxey-Mims, M.D., researcher and chief of the Children's National Division of Nephrology, only a fraction of patients meet that end goal. Instead, many patients achieve some reduction in proteinuria, but it'sbeen unclear whether those reductions lead to significant benefits for kidney health.

To investigate this question, Dr. Moxey-Mims and her colleagues used data from the National Institutes of Health-funded FSGS clinical trial that took place between November 2004 and May 2008. Participants in this study -- 138 patients who developed proteinuria due to FSGS between the ages of 2 and 40 and didn't respond to steroids -- received one of two different immunosuppressant regimens. They received frequent checkups including urinary protein tests during the duration of the study and were followed for a maximum of 54 months.

Results showed that about 49% of the study participants' proteinuria improved by 26 weeks of treatment on either regimen. More importantly, says Dr. Moxey-Mims, these patients retained significantly better kidney function over time, determined by a test called estimated glomerular filtration rate (eGFR), compared to those whose urinary protein remained high. The greater the reduction in proteinuria, the better their kidney function remained, and the longer their kidneys remained active before they developed ESKD.

"Even a modest reduction in proteinuria, as small as 20 or 30%, had an impact on these patients' kidney health," Dr. Moxey-Mims says.

Dr. Moxey-Mims notes that the finding could impact the design of clinical trials for FSGS treatments. Currently, these trials typically must include large numbers of patients to show a benefit if complete remission of proteinuria -- which only occurred in about 20% of patients in the National Institute of Diabetes and Digestive and Kidney Diseases trial -- is used as the end point.

If researchers use a range of proteinuria reduction as end points, she says, it could be easier to see if a drug or other intervention is working.

Similarly, she says, patients with FSGS and their doctors should view any proteinuria reduction as a positive.

"They shouldn't be discouraged if they can't reach full remission," Dr. Moxey-Mims says. "Doctors and patients alike can feel reassured that if they're reducing protein in the urine to some degree, then patients are getting some benefit."

Investing time in education in childhood and early adulthood expands career opportunities and provides progressively higher salaries. It also conveys certain benefits to health and longevity.

A new analysis published in the journal Psychological Science in the Public Interest (PSPI), however, reveals that even though a more extensive formal education forestalls the more obvious signs of age-related cognitive deficits, it does not lessen the rate of aging-related cognitive declines. Instead, people who have gone further in school attain, on average, a higher level of cognitive function in early and middle adult adulthood, so the initial effects of cognitive aging are initially less obvious and the most severe impairments manifest later than they otherwise would have.

"The total amount of formal education that people receive is related to their average levels of cognitive functioning throughout adulthood," said Elliot M. Tucker-Drob, a researcher with the University of Texas, Austin, and coauthor on the paper. "However, it is not appreciably related to their rates of aging-related cognitive declines."

This conclusion refutes the long-standing hypothesis that formal education in childhood through early adulthood meaningfully protects against cognitive aging. Instead, the authors conclude that individuals who have gone further in school tend to decline from a higher peak level of cognitive function. They therefore can experience a longer period of cognitive impairment before dropping below what the authors refer to as a "functional threshold," the point where cognitive decline becomes so obvious that it interferes with daily activities.

"Individuals vary in their rates of aging-related cognitive declines, but these individual differences are not appreciably related to educational attainment," notes lead author Martin Lövdén, formerly with the Karolinska Institute and Stockholm University in Sweden and now with the University of Gothenburg.

For their study, the researchers examined data from dozens of prior meta-analyses and cohort studies conducted over the past two decades. The new PSPI report evaluates the conclusions from these past studies to better understand how educational attainment affects both the levels of and changes in cognitive function in aging and dementia.

Although some uncertainties remain after their analysis, the authors note, a broader picture of how education relates to cognitive aging is emerging quite clearly. Throughout adulthood, cognitive function in individuals with more years of schooling is, on average, higher than cognitive function in those with fewer years of schooling.

This review highlights the importance of formal education for cognitive development over the course of childhood, adolescence, and early adulthood. According to the researchers, childhood education has important implications for the well-being of individuals and societies not just during the years of employment, but throughout life, including old age. "This message may be particularly relevant as governments decide if, when, and how to reopen schools during the COVID-19 pandemic. Such decisions could have consequences for many decades to come," said Tucker-Drob.

The authors conclude that improving the conditions that shape development during the first decades of life carries great potential for improving cognitive ability in early adulthood and for reducing public-health burdens related to cognitive aging and dementia.

Oxytocin, produced by the hypothalamus and sometimes known as the "love hormone" for its involvement in pair bonding and orgasm, can be a strong ally in the control and prevention of osteoporosis, according to a study by scientists at São Paulo State University (UNESP) in Brazil.

The study showed that when administered to female rats at the end of their fertile period, the hormone reversed precursors of osteoporosis, such as reduced bone density, decreased bone strength and a lack of substances that promote bone formation.

"Our research focuses on the prevention of primary osteoporosis, so we investigate physiological processes that occur during the premenopausal period. In this part of a woman's life, measures can be taken to prevent bone brittleness and fractures, which lead to lower quality of life and can shorten life expectancy," said Rita Menegati Dornelles, a researcher affiliated with UNESP's Araçatuba Dental School (FOA). Dornelles heads the Endocrine Physiology and Aging Laboratory in the school's Department of Basic Sciences.

The study was supported by São Paulo Research Foundation - FAPESP. A description of the study is published in Scientific Reports.

According to Dornelles, the important hormonal milestones in a woman's life are puberty and perimenopause, a transitional period starting some years before menopause itself as the ovaries gradually begin to produce less estrogen. These milestones mark the beginning and end of fertility, respectively.

"There's a lot of research on the postmenopause phase, which follows a woman's last period, but hormone swings in perimenopause are already sharp and are associated with a gradual decrease in bone density," Dornelles said. "More research is needed to support the prevention of osteoporosis during perimenopause, as the period after menopause represents about a third of a woman's life and should have the best quality possible."

In the study, the researchers administered two doses of oxytocin 12 hours apart to ten female Wistar rats. They were 18 months old, an unusually advanced age for laboratory rats, which have an average life expectancy of three years. Most in vivo experiments involve young rats that have been ovariectomized, i.e., had their ovaries surgically removed. The study involved rats in "peri-estropause", considered to be the equivalent of perimenopause in humans, that were undergoing a natural aging process.

Thirty-five days after oxytocin was administered, the researchers analyzed blood samples and samples of tissue from the femoral neck (the upper portion of the femur just below the hip joint and the most common location for a hip fracture), comparing the results with those for ten 18-month-old female Wistar rats that were not given the hormone.

There was no evidence of osteopenia (loss of bone density) in the animals treated with oxytocin, in contrast with the control group. "Our results demonstrated that oxytocin helps to modulate the bone remodeling cycle in senescent rats," Dornelles said. "The animals that received the hormone displayed an increase in biochemical markers associated with bone renewal and in the expression of proteins that support bone formation and mineralization."

Analysis of the blood samples showed increased activity of key bone formation markers, such as alkaline phosphatase. "This substance is produced by osteogenic cells and associated with mineralization. We also observed reduced activity of tartrate-resistant acid phosphatase, a marker of bone resorption," Dornelles said.

The rats treated with oxytocin had denser bones. "We found the femoral neck region to be stronger and less porous. Its biomechanical compression response was better, and it had physico-chemical properties that guaranteed higher density," she said.

Secreted in bone

Oxytocin is produced by the hypothalamus and released by the pituitary gland. Scientists discovered early in the twentieth century that its release is associated mainly with childbirth and breastfeeding. More recent studies have shown that many other cells also secrete oxytocin.

"It's secreted by bone cells, and our research has evidenced its association with bone metabolism in females during the aging process. Osteoporosis is more frequent among postmenopausal women, who generally tend to have lower blood plasma levels of oxytocin," Dornelles said.

The UNESP research group has been studying the involvement of oxytocin in bone metabolism for ten years. "In this time span, we've succeeded in characterizing animal models that simulate perimenopause in women," Dornelles said.

More broken bones

According to the World Health Organization (WHO), the number of hip fractures associated with osteoporosis is projected to increase 630% in Brazil by 2050, compared with 50% in developed countries. "The rise has to do with the aging of the Brazilian population," Dornelles said, adding that quality of life, diet and physical exercise are all important disease prevention factors.

In the study, the researchers focused on the femoral neck because it is the most common location for hip fractures, which are three times as frequent in women as in men. "The consequences of these fractures are very drastic, including loss of mobility and comorbidities," Dornelles said, adding that hip fractures are associated with high mortality rates: 24% of patients die within 12 months of a hip fracture, and the heightened risk of death can persist for at least five years.

"Loss of function and independence is profound among survivors," she said. "Approximately 40% become unable to walk independently, and about two-thirds of these need help a year later. Less than half recover their previous level of function."

In the future, researchers plan to study the effects of oxytocin on osteoporosis prevention in humans. "The hormone is naturally produced in our organism and has been synthesized in the lab. Even so, a long study will be needed to assess its safety and effectiveness and to estimate the appropriate dosage," Dornelles said.

CHICAGO (August 10, 2020): The rise in firearm violence has coincided with an increase in the severity of injuries firearms inflict as well as the cost of operations to treat those injuries; policy makers must be more aggressive in addressing violence to curb these trends, researchers report in a large national study of gunshot wounds that appears as an "article in press" on the Journal of the American College of Surgeons website ahead of print.

"Taken together, our findings suggest that gun violence has increased in numbers, at least for the sector that meets surgical criteria, and that these injuries result in a substantial financial burden in addition to the obvious psychosocial burden and other downstream effects," said lead study author Peyman Benharash, MD, MS, with the Cardiovascular Outcomes Research Laboratories and an associate professor-in-residence of surgery and bioengineering at the David Geffen School of Medicine at the University of California Los Angeles. "We hope that our findings are able to better inform policy in terms of violence prevention as well as reimbursement to hospitals, which are often in underserved regions, that care for these patients."

The study authors note that gun violence overall carries an annual cost to the U.S. health care system of $170 billion, with $16 billion for operations alone. The researchers used the National Inpatient Sample (NIS) to identify all hospital admissions for gunshot wounds (GSW) from 2005 through 2016. The researchers did not look at all adult GSW victims admitted to the hospital, estimated at 322,599, but only at the 262,098 victims who required at least one major operation.

Dr. Benharash explained the rationale for the study. "We're now seeing a lot more on the impact of gun violence," he said. "In the past, gun violence was never really discussed in the open; it was thought to only affect a certain population. However, now we know that it affects everyone. In the hopes of trying to reduce it at a systemic level from top to bottom, we're reporting, as surgeons, how gun violence in the patients that we treat has changed over the last decade."

The costs for hospitalizations, measured as median costs adjusted for gross domestic product, increased more than 27 percent over the 12-year study period, from $15,100 to $19,200 (p

The cost analysis categorized operations by type and three different cost ranges: low, medium and high, with average costs of $7,400, $17,200, and $58,800, respectively. "We found that compared with those who were not operated on, patients having head-neck, vascular, and gastrointestinal operations had increased odds of being in the high-cost tertile," Dr. Benharash said. "Being in the Western United States was also a predictor [of being in the high-cost tertile], as was being of Black race and having insurance by Medicaid. So there are certainly disparities that are socioeconomic in origin as well."

For example, the study found that while 3.4 percent of all patients had operations for head and neck injuries, these operations were disproportionately represented in the low- and high-cost ranges, accounting for only 0.81 percent of the former but 7.1 percent of the latter. "Gunshot wounds to the neck, for example, can be very costly because they can affect many delicate structures as compared with lower extremities, and these patients often require extensive hospitalization and a greater number of procedures" Dr. Benharash said.

The finding that costs in the West were higher is also important, Dr. Benharash noted, because it's in line with what other studies have reported with other specialties. "It's very important for policy makers and health services researchers to evaluate the disparities in cost," he said.

The improved survival of GSW patients is a function of improvements in trauma transport from the field, better prehospital resuscitation, and improved techniques, patient management and adjunct therapies once they get to the hospital, Dr. Benharash said. "It appears that patients are reaching surgery more often because of reduced mortality before they get to the hospital," he said.

The study also attributed these improvements in survival to efforts by the American College of Surgeon's Committee on Trauma, including the Advanced Trauma Life Support curriculum and Stop the Bleed® campaign. The latter trains the public in techniques to stop life-threatening bleeding in everyday emergencies.

But those improvements don't obviate the need for addressing the underlying problem, Dr. Benharash noted. "It's very important to put it in perspective that this entity is quite economically burdensome," he said. "If you're looking at prevention vs. treating a gunshot wound from an economic standpoint, it would make sense to invest in anti-violence interventions that can reduce assaults that are often preventable."

Suicide is another issue that must be addressed, he added. "The group of patients who self-harmed actually had the highest mortality overall," Dr. Benharash said. "This situation points again to the need for better mental health access that hopefully leads to a reduction in suicide attempts."

It is conventional wisdom that Americans cherish democracy -- but a new study by Yale political scientists reports that only a small fraction of U.S. voters are willing to sacrifice their partisan and policy interests to defend democratic principles.

The study, published in the American Political Science Review, found that only 3.5% of U.S. voters would cast ballots against their preferred candidates as punishment for undemocratic behavior, such as supporting gerrymandering, disenfranchisement, or press restrictions.

"Our findings show that U.S. voters, regardless of their party affiliation, are willing to forgive undemocratic behavior to achieve their partisan ends and policy goals," said Milan Svolik, professor of political science in the Faculty of Arts and Sciences and co-author of the study. "We find that polarization raises the stakes of elections and, in turn, the price of prioritizing democratic principles over partisan interests. Voters' willingness to sacrifice democratic principles may not be desirable in terms of protecting democracy, but it has an intuitive political logic: They are trading off one political interest against another."

Svolik and co-author Matthew Graham, a Ph.D. candidate in the Department of Political Science, conducted two experiments. One was an original, nationally representative survey experiment that asked respondents to choose among candidates, some of whom took positions violating key democratic principles. The other was a natural experiment the researchers conducted based on Montana's 2017 special election for the U.S. House of Representatives, in which Republican candidate Greg Gianforte physically assaulted a journalist who had repeatedly asked him a question about health policy on the night before the election.

In the survey experiment, respondents were presented with a series of choices between hypothetical candidates for a state legislature. Candidates were randomly assigned attributes, including race, gender, party affiliation, and positions on economic and social issues. In four of the scenarios, both candidates adopted democratically neutral positions. In seven others, one of the candidates was randomly assigned an undemocratic position, such as support for gerrymandering or ignoring unfavorable court decisions.

Overall, candidates who embraced an undemocratic position lost about 11.7% of their vote share. This may have been exacerbated by the randomized nature of the experiment, which assigned some hypothetical candidates highly unlikely attributes, such as a Democrat who supports tax cuts for the wealthy. When the researchers focused on choices respondents were more likely to encounter in the real world because candidates' adopted conventional positions for their respective parties, they found that just 3.5% of respondents would vote against their partisan interests to protect democratic principles. This reflects the consequences of political polarization, said the researchers: When party and policy are closely aligned, opposing candidates become increasingly ideologically distinct from each other, raising the price that voters must pay to punish their preferred candidate for undemocratic behavior by voting for the other candidate.

In 2016, only about 5% of U.S. House district candidates won their seats by a margin of less than 7% -- making the potential loss of 3.5% in vote share unlikely to deter candidates from engaging in undemocratic behavior, the researchers said.

"Our findings suggest that in the overwhelming majority of House districts, a majority-party candidate could get away with openly violating a democratic principle," said Graham. "Voters make tradeoffs. For the most part, people support candidates who share their partisan, ideological, or policy goals, even if that means condoning undemocratic behavior."

When Gianforte body-slammed a reporter in his campaign office the night before Montana's 2017 congressional election, more than half of voters had already cast absentee ballots. This allowed the researchers to compare votes cast for the same pair of candidates before and after the election-eve assault. In politically moderate precincts, voters who cast ballots on Election Day punished Gianforte for the assault on the journalist by voting across party lines. In hardline Republican precincts, significantly fewer voters punished Gianforte for his undemocratic behavior on Election Day, according to the study.

The researchers assert that their findings expose a blind spot in conventional methods of measuring support for democracy, which often involve asking people questions like: "Democracy may have problems, but it is better than any other form of government. To what extent do you agree or disagree with this statement?"

"Conventional measures don't capture people's willingness to act on their commitment to democratic values when doing so is politically costly," Svolik said. "If, as we found, only a small percentage of voters are willing to punish undemocratic behavior by their favored candidates in one of the world's oldest democracies, then we shouldn't be surprised by voters' failure to stop aspiring autocrats in younger democracies like Turkey, Hungary, or Venezuela."

Concern over the safety of students, teachers, and administrators in U.S. schools continues to grow, in part as a result of school shootings. In response, partnerships between schools and law enforcement agencies have increasingly placed school resource officers (SROs) in schools to boost security. Amid controversy over this practice, a new longitudinal study sought to learn more about the impact of SROs. The study found that schools that increased staffing levels of SROs were more likely to record increases in crimes and to exclude students from school in response to those crimes than schools without increases in SRO staffing levels; moreover, the increases in crimes and exclusions recorded persisted for up to 20 months.

The study, by researchers at the University of Maryland and Westat, appears in Criminology & Public Policy, a publication of the American Society of Criminology.

"Our findings suggest that increasing SRO staffing in schools does not improve school safety and that increasing exclusionary responses to school discipline incidents increases the criminalization of school discipline," according to Denise C. Gottfredson, professor emerita at the University of Maryland Department of Criminology and Criminal Justice, who led the study with Scott Crosse, former associate area director at Westat. "We recommend that educational decision makers seeking to enhance school safety consider alternatives to programs that require regular police presence in schools."

The study examined the effects over time of an increase in SRO staffing on 33 public middle and high schools in California; the schools enhanced SRO staffing through funding in 2013 or 2014 from the U.S. Department of Justice's Community Oriented Policing Services Hiring Program. Looking at disciplinary offenses and actions, the study compared these 33 schools with 72 schools that were similar in terms of prior disciplinary actions and demographic characteristics but did not increase SRO staffing during the same period. Short-term effects were measured two and three months after staffing rose, and long-term effects were calculated 11 and 20 months after the staffing increase. Data came from schools' administrative records, surveys of school administrators, and interviews with law enforcement officers, including SROs.

The study found that when schools increased SRO staffing, drug- and weapons-related offenses increased immediately, and that this rise persisted for 20 months. The number of exclusionary disciplinary actions taken against students also increased immediately after the rise in SRO staffing, and this increase persisted for 11 months. The findings were significant for students without special needs but not for students with special needs, the study found.

Based on the study's surveys and interviews, the authors suggest that increases in school disciplinary offenses due to increased SRO staffing levels may be the result, at least in part, of increased surveillance. But their concern is that these increases in offenses did not level off after the initial rise in SRO staffing, but rather persisted for months.

Among the study's limitations, the authors acknowledge that the outcome measures used might have been influenced by the increase in SRO staffing levels. While this creates ambiguity around the interpretation of how having more SROs increases recorded crime, it does not question the finding that the presence of SROs boosts the number of recorded crimes and exclusionary responses to these crimes. Furthermore, because the study looked only at schools in California, its findings are not generalizable to schools in other states. Finally, data on students without special needs included only infractions that resulted in removing a student from school for one or more days, which likely omitted many lower-level offenses and therefore reduced variability in several outcomes.

"Our study demonstrates that increasing SRO staffing in schools boosts the number of exclusionary responses to disciplinary infractions, which can have serious consequences for students," notes Crosse. "These include contributing to a school-to-prison pipeline by increasing formal responses to behaviors that otherwise would have been undetected or handled informally."

When the U.S. flooded Panama's Chagres River valley in 1910, Gatun Lake held the record as the world's biggest reservoir. This record was surpassed, but researchers at the Smithsonian Tropical Research Institute (STRI), who are now studying invading lizards on the tiny islands that dot the lake, discovered that islands with native lizards act as another kind of reservoir, harboring the parasites that control invaders. The study, published in the journal Biology Letters, is valuable experimental evidence that biodiversity is better, making ecosystems more resistant to invasion.

As part of another study to find out how many generations it takes for slender anole lizards (Anolis apletophallus) to adapt to climate change, a research team led by Christian Cox, a visiting scientist at STRI from Florida International University, and Mike Logan from the University of Nevada, Reno, transplanted lizards from the tropical forest on the mainland to the islands, which tend to be hotter and drier. Before the transplant, they did a general health check of the lizards that included counting the number of parasites (mites) on their bodies.

When they came back several times during the next two years to see how the lizards were doing in their new habitats, they recounted the number of mites.

"We found that on the islands with no resident species of anole lizard, the slender anole lizards that were transplanted to the islands lost their mites within a single generation, and the mites are still gone several generations later (up until the present)," Cox said. "Indeed, individual founding lizards that had mites during the initial transplant had no mites when they were later recaptured. In contrast, anole lizards that were transplanted to an island with another resident (native) species of anole lizard kept their mites for three generations, and some of the founders on the two-species island never lost their mites."

"Our study turned out to be a large-scale experimental test of the enemy release hypothesis," said Logan, who did this work as a three-year STRI/Tupper postdoctoral fellow. "Often, when an invasive animal shows up in a new place, all of its pathogens and parasites are left behind or do not survive, giving it an extra survival advantage in the new place: thus the term enemy release."

The team also found that the two-species island had lower density and lower biomass per unit area of the invasive lizard species, indicating that the continued presence of the mites may be keeping their populations under control.

"Our study is a clear example of something that conservationists have been trying to communicate to the public for some time," Logan said. "Diverse native communities sometimes function as 'enemy reservoirs' for parasites and diseases the keep down the numbers of invaders."

FAIRFAX, Va. -- Expanding standard techniques during mechanical thrombectomy -- a procedure that removes a clot from an artery during stroke -- allows researchers to reproducibly obtain and study local leukocyte populations during human stroke, according to a study by the University of Kentucky Department of Neurology, released today at the Society of NeuroInterventional Surgery's (SNIS) 17th Annual Meeting.

The study, Changes in Leukocyte Distribution in Intracranial vs. Systemic Blood Collected during Mechanical Thrombectomy, started with the established BACTRAC protocol and modified the tissue collection protocol to isolate lymphocytes for flow cytometry and to bank the thrombus and plasma. The researchers first established the protocol in healthy controls using venous blood samples and then initiated for thrombectomy cases.

These methods can be used to expand our understanding of acute inflammatory mechanisms activated within the infarcted brain. This novel approach may be critical to identifying immunotherapeutic targets that can be delivered either as adjunctive therapies to mechanical thrombectomy, or in the phases of recovery after stroke.

"This modification to the existing BACTRAC protocol provides the opportunity, for the first time, to study changes in local leukocyte populations with flow cytometry in the arteries undergoing ischemic stroke in the human condition," said co-senior authors of the study Dr. Justin Fraser, Department of Neurosurgery, and Dr. Ann Stowe, Department of Neurology, both at the University of Kentucky. "Efficient processing of lymphocytes with subsequent flow cytometry analyses will provide important insight into the neuroinflammatory microenvironment of the occlusion during stroke."

Researchers will focus future studies on investigating changes in specific leukocyte populations and how they might relate to patient demographics, patient co-morbidities, infarct volume, and functional recovery. These data will help accelerate translational stroke research to illuminate new approaches for drug discovery and prognosis.