Culture

Study finds association between therapy time, length of stay after hip fracture surgery

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.

Credit: 
George Washington University

Survival of preterm babies improves by 25% after quality-improvement program

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

Credit: 
Canadian Medical Association Journal

Burden of health care costs greatest among low-income Americans

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."

Credit: 
RAND Corporation

Revving up the engine

video: HCM cells (right) show a markedly different contraction patterns than normal heart cells.

Image: 
Seidman lab/Harvard Medical School

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.

Credit: 
Harvard Medical School

Study reveals similar survival of African-American and white men with prostate cancer in an equal-access health care system

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.

Credit: 
Wiley

Strict adherence to traditional masculinity associated with more severe PTSD in vets

To help service members perform better in the field, military training emphasizes the importance of certain traits associated with traditional masculinity, including suppression of emotion and self-reliance. But when veterans return home, strict adherence to these traits can become detrimental, leading to more severe post-traumatic stress disorder symptoms and making it more difficult to treat, according to research published by the American Psychological Association.

"These findings suggest that veterans with rigid adherence to traditional masculinity may be at increased risk for developing PTSD, may have more severe PTSD symptoms and may be less likely to seek mental health treatment for PTSD," said Elizabeth Neilson, PhD, of Morehead University and the lead author on the study.

The research was published in the journal Psychology of Men and Masculinities.

Neilson and her co-authors analyzed data from 17 studies, comprising more than 3,500 military veterans, conducted in the last 25 years that involved, at least in part, measuring the relationship between adherence to traditional masculine ideals and trauma-related symptoms. The studies primarily focused on men, but one included both male and female participants. While most studies were conducted in the United States, the researchers also included studies from Canada, the United Kingdom, Israel and Vietnam.

"Overall, we found that strict adherence to masculine norms was associated with more severe PTSD symptoms in veterans, but more detailed analysis suggests that the association may specifically be caused by the veterans' belief that they should control and restrict their emotions. In other words, they should be tough," Neilson said. This held true for both male and female veterans.

While all members of society are exposed to aspects of traditional masculinity, members of the military receive messages that normalize, reinforce and instill values of masculinity as part of their training, according to Neilson.

"Previous research has found that military personnel report high levels of conformity to traditional masculine norms, such as emotional control, self-reliance and the importance of one's job," she said. "These values can promote self-confidence and skill-building in the field, but when a service member is confronted with physical or mental trauma, they can also contribute to more severe PTSD."

Traumatic experiences, including combat and sexual trauma, can lead to feelings of powerlessness and hopelessness, both of which are in direct opposition to what society expects of men: That they should be strong and in control. The discrepancy between reality and societal expectations can exacerbate PTSD symptoms. Research estimates as many as 23% of veterans returning from Iraq and Afghanistan experience PTSD.

Adherence to masculine norms can also create barriers to getting necessary treatment, according to Neilson. Previous research on veterans returning from the wars in Iraq and Afghanistan found pride in self-reliance and a belief that one should be able to handle mental health problems on one's own kept service members from seeking help when they needed it.

And even if veterans did seek treatment, the emphasis on stoicism and mental fortitude within both military culture and traditional masculinity could make treatment more difficult, she said. The two most widely used, evidence-based therapies for PTSD require explicit discussions of emotions, thoughts and behaviors related to traumatic experiences. PTSD is perpetuated by avoiding stimuli associated with a traumatic experience, including emotions. Successful PTSD treatment involves breaking that cycle of avoidance and confronting those stimuli, she said.

"Both military culture and traditional masculine ideals lead to the avoidance of disclosure and speaking about traumatic experiences, which may interfere with appropriate treatment," Neilson said.

Another trend the researchers found was that veterans often try to reaffirm their masculinity following trauma, engaging in exaggerated stereotypical male behavior, such as aggression and increased sexual behavior, to compensate for the injury the trauma had on their identity, according to Neilson.

"In one study we reviewed, veterans reported engaging in frequent sex to avoid negative thoughts, because feeling sexually desirable temporarily suspended those negative thoughts about their self-worth," she said.

APA published voluntary guidelines in 2018 recommending that therapists consider discussing masculine ideology and the effects of cultural expectations of men and boys when treating male veteran clients. Neilson hopes that future research will examine how clinicians already are addressing conformity to masculinity ideology in their treatment of PTSD.

"It would not surprise me if some clinicians are already considering how a veteran's masculinity ideology contributes to their PTSD symptomology and treatment engagement," she said. "Consistent with APA's recommendations, I suggest that clinicians discuss beliefs and adherence to traditional masculinity ideologies with the patients. This information is important for conceptualizing patients' mental health and identifying specific behaviors to target in treatment."

Credit: 
American Psychological Association

Climate costs smallest if warming is limited to 2°C

"To secure economic welfare for all people in these times of global warming, we need to balance the costs of climate change damages and those of climate change mitigation. Now our team found what we should aim for," says Anders Levermann from the Potsdam Institute for Climate Impact Research (PIK) and Columbia University's LDEO, New York, head of the team conducting the study. "We did a lot of thorough testing with our computers. And we have been amazed to find that limiting the global temperature increase to 2°C, as agreed in the science-based but highly political process leading towards the 2015 Paris Agreement, indeed emerges as economically optimal."

Striving for economic growth

Climate policies such as for instance the replacement of coal-fired power plants by windmills and solar energy, or the introduction of CO2 pricing, have some economic costs. The same is true for climate damages. Cutting greenhouse gas emissions clearly reduces the damages, but so far observed temperature-induced losses in economic production have not really been accounted for in computations of economically optimal policy pathways. The researchers now did just that. They fed up-to-date research on economic damages driven by climate change effects into one of the most renowned computer simulation systems, the Dynamic Integrated Climate-Economy model developed by the Nobel Laureate of Economics, William Nordhaus, and used in the past for US policy advice. The computer simulation is trained to strive for economic growth.

"It is remarkable how robustly reasonable the temperature limit of more or less 2°C is, standing out in almost all the cost-curves we've produced," says Sven Willner, also from PIK and an author of the study. The researchers tested a number of uncertainties in their study. For instance, they accounted for people's preference for consumption today instead of consumption tomorrow versus the notion that tomorrow's generations should not have less consumption means. The result that the 2°C limit is the economically most cost-efficient one was also true for the full range of possible climate sensitivities, hence the amount of warming that results from a doubling of CO2 in the atmosphere.

"The world is running out of excuses for doing nothing"

"Since we have already increased the temperature of the planet by more than one degree, 2°C requires fast and fundamental global action," says Levermann. "Our analysis is based on the observed relation between temperature and economic growth, but there could be other effects that we cannot anticipate yet." Changes in the response of societies to climate stress - especially a violent flare-up of smoldering conflicts -, or the crossing of tipping points for critical elements in the Earth system could shift the cost-benefit analysis towards even more urgent action.

"The world is running out of excuses to justify sitting back and doing nothing - all those who have been saying that climate stabilization would be nice but is too costly can see now that it is really unmitigated global warming that is too expensive," Levermann concludes. "Business as usual is clearly not a viable economic option anymore. We either decarbonize our economies or we let global warming fire up costs for businesses and societies worldwide."

Credit: 
Potsdam Institute for Climate Impact Research (PIK)

Consequences of Zika virus attack on glial cells

image: The Zika virus is highlighted in green, as the astrocyte nucleus is in blue and its cytoplasm in red.

Image: 
Karina Karmirian and Pítia Ledur

Previous studies regarding the damage of the Zika virus on the brain had already pointed out the virus's predilection for a certain neural cell: the astrocyte. However, few studies have proposed to identify the infection effects on these cells, as well as their association with developmental alterations, including brain malformations and microcephaly. Recently published in the Scientific Reports journal, a new article sought to unravel the virus reactions on laboratory-created astrocytes, comparing them to the same cells present in the brain tissue of animals and fetuses infected with Zika.

Marked by their branched-tipped structure and vast abundance in the human brain tissue, astrocytes are named after the Greek word for stars. Entangling our sovereign organ, this neural constellation has a fundamental role on our cognitive functions, since it provides metabolic support for neuron cells, participates in the formation of synapses and also composes the blood-brain barrier, a structure that selects the entrance of substances in the brain, protecting it from harmful toxins. The study carried out by the D'Or Institute for Research and Education (IDOR), in partnership with the Federal University of Rio de Janeiro (UFRJ) and other Brazilian institutions, found that part of the neural complications caused by Zika might be related to its damage on astrocytes, which would also contribute to the appearing of brain malformations.

The corresponding author of the article was the neuroscientist Stevens Rehen, a researcher at UFRJ and IDOR involved in several other studies related to Zika, including the first publication to analyze the effects of the virus on laboratory-developed human mini-brains. In the most recent article, Rehen and his team uncovered the changes that this viral infection causes in developing neural cells, as well as their consequences for brain development. "The scientific literature had already identified Zika's attack on astrocytes, but until now, no study had focused on understanding how it affects its functioning," says Karina Karmirian, a member of Rehen's group and one of the first authors of the study. Among the damages that the virus causes to these cells are the overload of its mitochondria, DNA breakage, and oxidative stress, the latter being a common disturbance to premature aging, cancer, and neurodegenerative diseases.

Multiple Analyzes

To achieve the scope of the research, the scientists created separately 3 cell types that are present in the human fetal brain: astrocytes, neurons, and neural stem cells. When infected with the Zika virus, the most severe damages were proven in astrocytes, whose organelles responsible for cellular respiration -- the mitochondria -- started to excessively produce free radicals, generating oxidative stress and changes in their morphology. In addition to the high percentage of cell death, many surviving astrocytes also revealed reduced and irregular cell nuclei after the infection.

Helena Borges, a professor at UFRJ and one of the researchers in the study, detailed why the damage caused by the Zika virus can be permanent in astrocytes. "To repair double-strand DNA breaks, there are two main types of DNA repair: one that uses an entire copy of DNA as a template - the homologous recombination - and a faster repair mechanism yet potentially subject to mutation, which dispenses the presence of an integrated DNA copy: the non-homologous recombination. Proliferating cells, like neural stem cells, can use both repair mechanisms. However, differentiated cells such as astrocytes have a reduced chance of homologous recombination, increasing the chance of permanent mutations appearing in these cells", explains the expert.

The research also analyzed materials regarding brain tissues of fetuses that didn't survive the infection. Scientists have identified greater signs of inflammation in fetal astrocytes, confirming the relevance of these cells on the virus attack pattern. The same inflammatory profile was identified in animal studies: mice infected with the Zika virus also revealed greater vulnerability in their astrocytes, in comparison to neurons. Microglial cells -- which, like astrocytes, are responsible for supporting neurons -- were also notably infected during the process. "These cells have an immune function in the brain and reached an inflammation level close to that of astrocytes during the experiments. The neurons themselves have a low infection, but they depend on communication between astrocytes and microglia for a healthful performance. This leads us into assuming in which way neurons could also be affected in the long term, due to the action of Zika in these cells that are essential to their functioning", informs Karmirian.

The findings on the Brazilian research lead scientists to conclude that, due to the crucial role of astrocytes in the upgrowth and functioning of the brain, their imbalance during neural development should contribute to serious health implications throughout life. This regards not only brain malformations such as microcephaly, but possibly other neurological disorders that could manifest in the adulthood of those infected in the womb, regardless of apparent malformations. The researchers say that due to the fledgling of long-term studies regarding Zika, further investigations will still be needed to determine the consequences of its infection on both children and adults, as possible neurological problems may occur subsequent to the extended action of the virus on young astrocytes.

Credit: 
D'Or Institute for Research and Education

Research shows the sexes have equal spatial cognition skills

image: Research by Drs Mark Campbell and Adam Toth of Lero, the Science Foundation Ireland Research Centre for Software and University of Limerick, Ireland shows that men and women have equal spatial cognition skills. Pictured at the launch of the Lero Esports Science Research Lab are Jessica Mangione, Niall Ramsbottom, Dr Adam Toth, Yueying Gong and Dr Mark Campbell.

Image: 
Diarmuid Greene, TrueMedia

Men are not better than women at spatial cognition - such as map reading - is the principal finding from ground-breaking work by researchers at Lero, the Science Foundation Ireland Research Centre for Software, hosted at University of Limerick (UL), Ireland.

Employing cutting-edge eye-tracking technology researchers Dr Mark Campbell and Dr Adam Toth of the Lero Esports Science Research Lab at UL found that there is no male advantage in mental rotation abilities associated with spatial cognition competences.

Dr Campbell said the skill of spatial cognition or our ability to navigate our environment has been the battleground for almost 40 years for researchers claiming that males have a distinct performance advantage on tests of spatial cognition, notably the mental rotations test.

Studying the cognitive proficiency of individuals and gamers is a key aim of the Lero Esports Science Research Lab which opened in 2019 and is the first of its kind in Ireland.

"Better performance on these tests is strongly associated with higher IQ and better performance in STEM (Science Technology Engineering and Maths) subjects in schools and colleges," Dr Campbell explained.

Dr Toth sums up the results: "So males are better than females? Well no, actually. Our study found that there is no male advantage in mental rotation abilities. By lengthening the time allowed to complete the test, the male performance advantage diminished entirely suggesting that the so-called sex difference in mental rotation is simply not there or may be explained by other factors."

The research published in Nature Scientific Reports also found for the first time that both males and females frequently employed different gaze strategies during the cognitive tests to get to the correct answer. In other words, men and women approach the task in a different way to get the same result.

The research paper is entitled: "Investigating sex differences, cognitive effort, strategy, and performance on a computerised version of the mental rotations test via eye-tracking."

One hundred University of Limerick (UL) undergraduate and postgraduate level psychology and sports science students volunteered to take part in the test carried out by the Lero researchers. The 47 men and 53 women were in good health and had an average age of 23.

Credit: 
University of Limerick

A new model has been developed that simulates the accumulation of lipids in membranes

image: Vladimir Baulin, researcher of the URV's Department of Chemical Engineering, has led the study.

Image: 
URV

Cholesterol is crucial to the formation of the cell membranes of mammals and is part of many life processes. One of the most controversial concepts in biophysics is the hypothesis of the so-called lipid rafts: areas of high concentrations of cholesterol and glycosphingolipids in membranes. These lipid rafts, also known as lipid microdomains, are areas of the cell membrane in which lipids and cholesterol accumulate and play an important role in cell function. Currently, the presence of lipid rafts in live cells is only a hypothesis because although various laboratory studies have attempted to simulate them by mixing two types of lipid and cholesterol, none has managed to detect them or determine whether they really exist, how they are formed and how they function in live cells.

It is suspected that lipid rafts are also responsible for the onset of diseases such as Creutzfeldt-Jakob or AIDS, the pathogens of which pass through them to enter the cells. Therefore, understanding their mechanism is fundamental to determining how these diseases develop.

A team of physicists led by the researcher of the URV's Department of Chemical Engineering Vladimir Baulin has designed an experiment that simulates the formation of a new type of lipid raft on a nanometric scale around objects incrusted in the membranes such as proteins and ion channels. The results of this study have been published in the journal Physical Review Letters.

"Ion channels are a sort of transmembrane protein - that's to say, they span the whole cell membrane - which, in conjunction with proteins, allow specific ions to pass from one side of the membrane to the other. They are part of it and contain cholesterol. The role transmembrane proteins play in the possible formation of these cholesterol nanodomains is unknown," says Vladidimir Baulin about the research results.

In this research, the scientists have carried out an experiment with a lipid membrane very similar to human cells in terms of the size scale, and the dimension and composition of the cholesterol. They substituted the transmembrane protein for an ultra-short carbon nanotube - 10 nanometres long. And after a series of simulations they confirmed that these domains - the lipid rafts - are highly dynamic, they form and then disappear only to form again and they exist for approximately 10 nanoseconds.

The team also made another important discovery about the role of cholesterol in membranes: cholesterol may be responsible for destabilizing the membranes and helping nanometric-sized objects to enter the cells. "It was like finding the key for opening and closing doors through a membrane," said Vladimir Baulin. "We found that when there are high concentrations of cholesterol, nanotubes can spontaneously leave the membrane in a question of milliseconds. But if the membrane has no cholesterol, they remain trapped inside."

This study may serve to develop new crucial approaches for researching lipid rafts, so the development of some diseases and cell processes will also be better understood.

Credit: 
Universitat Rovira i Virgili

Sea level rise to cause major economic impact in the absence of further climate action

The Paris Agreement, adopted in 2015 by 175 parties, aims to limit global warming to well below 2°C compared to pre-industrial levels. However, the period 2010-2020 was the planet's hottest decade on record and the long-term trend is upward. Sea level rise is one of the most severe impacts of climate change, with rising waters amplifying coastal floods, threatening coastal communities, infrastructure, and agriculture.

New IIASA-led research for the first time assessed the economy-wide effects of sea level rise globally and in particular in G20 countries when jointly taking into account different climate mitigation and adaptation assumptions, using three different macroeconomic models. In the study, authors compared two different climate policy scenarios - one achieving well below 2°C warming by the end of this century (basically in line with the Paris Agreement), and one overshooting this target - in combination with two different adaptation scenarios (no adaptation and full adaptation to sea level rise) and estimated GDP impacts due to coastal flooding in all scenario combinations for 2050 and 2100. The study is also innovative in terms of looking at G20 countries explicitly, that is, countries that are big emitters and at the same time affected by climate change. The analysis thus corroborates the need for action on both mitigation and adaptation.

"We found that up to 2050 the global GDP losses in both climate futures are significant and similar given the effects of climate change that we are already experiencing. However, by 2100, without further mitigation and adaptation and assuming continued sea level rise, projected annual global economy-wide losses can amount to more than 4%," explains study lead author and IIASA Risk and Resilience Deputy Program Director Thomas Schinko. "With ambitious mitigation and adaptation, the model results show that this number can be reduced to below 0.5% of global GDP loss, despite the associated costs for adaptation measures and residual impacts. This confirms the importance and economic efficiency of adaptation in the long term: Making sure that coastal communities and their infrastructure are climate-resilient will affect economies across the globe much less than persistent climate impacts in the absence of climate action."

According to study coauthor Laurent Drouet, a senior scientist at the RFF-CMCC European Institute on Economics and the Environment, in terms of regional effects across the G20, the highest levels of annual GDP impacts in relative terms are projected for China. In 2050 and with no further adaptation, economic losses amount to 0.8-1.0%. Estimated GDP losses for India are slightly smaller (0.5-0.6%), followed by Canada (0.3-0.4%). Zoi Vrontisi, a senior researcher at the E3MLab of the National Technical University of Athens, highlighted that until 2050 the direct economic losses of sea level rise on a global level can still be balanced out by interregional trade and substitution effects in production processes at the macroeconomic level. However, after 2050 and up to 2100, the scale of economy-wide effects in G20 countries changes drastically.

China remains the country with the highest projected relative GDP loss if no further adaptation is undertaken, which is now a factor of ten higher than it was in 2050: According to the economic modeling undertaken, annual losses would amount to 9-10% in a well below 2°C scenario, and to 11-12% under a current mitigation policy scenario. Other regions with severe economy-wide damages by 2100 under no adaptation are Europe and Japan.

Macroeconomic impacts are analogous to the direct damages of sea level rise. However, Andries Hof from PBL Netherlands Environmental Assessment Agency, notes that this changes if stronger mitigation actions are undertaken and sea level rise adaptation efforts are strengthened. Similar to the global picture, all individual G20 countries could thereby limit the residual economy-wide impacts to below 1.0% of GDP if appropriate adaptation measures are taken. An important benefit of further mitigation efforts to be undertaken by G20 countries are strong reductions of impacts for the most vulnerable coastal countries across the globe. This effect will be further investigated in future research.

"The findings of this paper demonstrate that we need to think long term while acting swiftly. Macroeconomic impacts up to and beyond 2050 as a result of coastal flooding due to sea level rise - not taking into account any other climate-related impacts, such as drought - are severe and increasing. We, as a global society, need to further coordinate mitigation, adaptation, and climate resilient development, and consider where we build cities and situate important infrastructure," concludes Schinko.

Credit: 
International Institute for Applied Systems Analysis

Physicists develop a new experimental model for 'lipid rafts' in human cells

It is a rather trivial statement: if you want to enter the house through a door, it is best to take a key in your hand, open and go inside. But if you have no idea what the key looks like or where it is hidden - under the doormat, on the basement stairs? - it becomes much more difficult.
 

It is similar in biology. It goes without saying that there are doors that connect the interior of cells to the exterior. One of these doors, however, still puzzles scientists: so-called "lipid rafts". These are certain areas in the cell membrane in which lipids, which are important for the signal transmission of cells, accumulate. These are platform enriched with cholesterol that looks like rafts, these areas "float" through the cell membrane. Across lipid rafts, molecules can also enter and get out of the cell.
 

In particular, scientists suspect that these "lipid rafts" are also contributing to diseases such as Parkinson, Alzheimer or HiV infection, whose pathogens enter the cells via these lipid raft. An understanding of this mechanism is therefore fundamental to the emergence of such diseases.
 

However, no one has been able to fully characterize "lipid rafts" in living cells, so far their size and lifetime are still subject to vigorous debates. Only in model membranes have the "rafts" been observed and fully characterize but "these models were not very well transmissible to real cells", explains Dr. Jean-Baptiste Fleury (Saarland University). The expert in microfluidics explains why this is the reason: "On the one hand, previous experiments were very large, namely in the micrometer range. At the cell level, however, the processes take place at the nanometer level, i.e. again by a factor of 1000 below. In addition, the lipid rafts in the experiment have been much more short-lived than in real cells", Fleury explains. Instead of between one and 15 milliseconds, the previous experimental lipid rafts existed only for about 10 nanoseconds, i.e. about one millionth of the natural lipid rafts.
 

Jean-Baptiste Fleury has now developed an experiment system that brings both the size scale, the temporal dimension of these lipid rafts much closer to the natural conditions than has been the case up to now. To do this, he placed around 10 nanometer long carbon nanotubes, as a replacement of an artificial transmembranar protein, inside the model membrane to trigger the formation of ultra-small cholesterol region around this carbon nanotube. He was able to observe that the cholesterol concentration plays a decisive role in whether the nanotubes got through the cell or whether they remained trapped in the cell membrane. "We found that nanotubes in presence of high cholesterol concentrations can spontaneously emerge from the bilayer within a few milliseconds while remaining trapped in the membrane if the bilayer does not contain cholesterol."

Theoretical physicists from the University of Rovira i Virgili in Tarragona (Spain) and the Nanjing University in China developed the basis for this. In months of computer simulations, they calculated the behavior of the nanotubes and cholesterol and then used the Saarland expertise of Jean-Baptiste Fleury as an experimental physicist to check the theoretical knowledge in the experiment. In this way, the international research team has developed fundamental new approaches to researching lipid raft, so that the development of diseases and the cellular processes may also be better understood. They published their findings in the renowned journal "Physical Review Letters". 

Credit: 
Saarland University

'Net' is closing in on more viable biological control options for fall armyworm menace

image: Fall armyworm (Spodoptera frugiperda) is seriously threatening food security as a pest of cereals

Image: 
Daniel Adjokatcher

The 'net' is closing in on more viable biological control agents to fight the scourge of the fall armyworm (FAW) pest which is already wreaking havoc in most African countries as well as more than a dozen Asian countries including China and India.

CABI scientists teamed up with colleagues from the International Institute of Tropical Agriculture (IITA) and the Plant Protection and Regulatory Services Directorate (PPRSD) in Ghana to conduct new research which is another step closer to finding more biological control options to fight the FAW menace.

The Food and Agriculture Organization of United Nations (FAO) states that, based on 2018 estimates from 12 African countries, up to 17.7 million tonnes of maize could be lost annually to FAW on the continent - enough to feed tens of millions of people. The most direct impact of these losses falls on smallholder maize farmers, most of whom rely on the crop to stave off hunger and poverty.

Lead authors Dr Lakpo Koku Agboyi, Dr Georg Goergen and Dr Marc Kenis led new research which focused on exploring the parasitoid complex of the FAW in Ghana and Benin where 10 species were found to have parasitized the pest. These included two egg parasitoids, one egg-larval, five larval and two larval-pupal parasitoids. In similar surveys carried out in Ethiopia, Kenya and Tanzania, seven parasitoid species were collected.

Outlining their findings in the journal Insects, the authors showed that the three most abundant parasitoids in both countries were two Braconidae: the egg?larval parasitoid Chelonus bifoveolatus and the larval parasitoid Coccygidum luteum, as well as the egg parasitoid Telenomus remus.

Dr Agboyi, who is based at CABI's centre in Ghana, said, "We determined the larval parasitism rates in three Ghanaian regions and averages varied from 5% to 38% between regions, with up to 75% parasitism found at single locations. This data provides an important baseline for the development of various biological control options for fall armyworm."

Back in April 2019 Dr Kenis was lead author on another paper in Insects which confirmed the first report of Telenomus remus in Africa and positioned the species as a 'great opportunity for the rapid deployment of a biological control agent' for fall armyworm on the continent.

The latest research adds weight to the scientists' suggestion that Chelonus bifoveolatus, Coccygidum luteum and Telenomus remus could all be used to fight the fall armyworm as part of an Integrated Pest Management plan, either as augmentative biological control agents through regular releases or in conservation biological control strategies in which cultural practices enhance the action of the main natural enemies.

Dr Kenis said, "In Latin America, field releases of Telenomus remus in maize can result in 80-100 percent parasitism, providing full control of fall armyworm. However, a challenge of using a larval parasitoid of fall armyworm in augmentative biological control will be to find alternate rearing hosts for mass production. Fall armyworm is not suitable for the mass production of larval parasitoids due to the cannibalistic behaviour of the larvae".

"Another consideration for a wider utilisation is to provide a product that is financially affordable for African farmers. Mass production on its natural hosts is costly but we believe rearing systems on factitious hosts can be developed."

"Understanding the parasitoid complex of the fall armyworm in Africa is also necessary before any development of classical biological control involving the introduction of parasitoids from the Americas. However, since FAW remains a huge problem for African farmers despite substantial parasitism by native parasitoids, the introduction of American parasitoids should not be ruled out since their successful establishment may lower pest population levels permanently, at no cost for the farmers."

Dr Agboyi adds that the use of broad-spectrum insecticides is not only unsustainable in the long-run, but also increases production costs, has biodiversity and environmental impacts, and poses health risks to the growers and consumers.

Biological control, on the other hand they say, can offer an economically and environmentally safer alternative to synthetic insecticides that are currently being used for management of the fall armyworm and a range of other crop pests.

Credit: 
CABI

Discovery of a new liquid-liquid interfacial deformation by partial miscibility

image: (a) Phase diagram of PEG 8000-Na2SO4-water system and solution systems used in the present study. Region I is a one-phase region and region II is a two-phase region. When the concentration is set in red triangle, the solution is separated into two phases, phase L and phase H. The solution compositions used in the immiscible, fully miscible, and partially miscible systems are indicated by red, black, and green circles, respectively. (b) When a more viscous liquid is injected from a single point into a Hele-Shaw cell (a gap between two parallel flat plates with a very small distance b (= 0.3 mm)) filled with a less viscous liquid, their interface becomes hydrodynamically stable and spreads out in a circle. (c) Hydrodynamically stable displacement in the immiscible, fully miscible, and partially miscible systems for a given flow rate. The pictures are taken when the longest radius of the displacement pattern is 42 mm and the injection time is shown at the lower right corner of each picture. The circles in the figure correspond to the circles in the phase diagram of (a). That is, in the immiscible system, the compositions of the more viscous solution and the less viscous solution are represented by open-circle in red and solid-circle in red. In the fully miscible system, the composition of the more viscous solution, of the less-viscous, and of their mixed solution are represented by open-circle in black, solid-circle in black, and star in black. In the partially miscible system, they are represented by open-circle in black, solid-circle in black, and star in green.

Image: 
Yuichiro Nagatsu/ TUAT

The international collaborative team of Tokyo University of Agriculture and Technology (TUAT) (Japan), IIT Ropar (India), Osaka Univ. (Japan) has discovered for the first time in the scientific development that "partially miscibility", in which the two liquids do not mix completely with finite solubility, is capable of deforming the liquid-liquid interface. This interfacial deformation originates due to the spontaneous motion driven by phase separation between the soluble species, and is a phenomenon that cannot be seen with completely mixed (fully miscible) with infinite solubility or (almost) immiscible with no solubility.

The researchers published their results in Physical Review Fluids on Oct 29th, 2019.

The process of displacing one fluid in a porous medium by injecting another fluid is important in reactions and separation in chemical processes, as well as in enhanced-oil-recovery and CO2 sequestration. In particular, when a less viscous fluid displaces a more viscous fluid, the interface between the two fluids becomes hydrodynamically unstable and deforms in a finger shape. This phenomenon is called "Viscous fingering", and it has been studied since the 1950s as one fluid dynamics problem. Now, it is widely known that the properties of these two fluids can be traditionally classified according to whether they are fully miscible or immiscible. On the other hand, when a more viscous fluid displaces a less viscous fluid, classically, the interface stably spreads, regardless of whether the two fluids are fully miscible or immiscible.

"It has long been known that two fluids are partially miscible in underground processes with high-pressure conditions, such as oil recovery and CO2 storage, "said Dr. Nagatsu, corresponding author on the paper and an associate professor in the Department of Chemical Engineering at TUAT. "However, the intricate understating of interfacial dynamics in partially miscible systems has not been well-studied. One of reasons is that fluid displacement research has been mainly conducted by fluid mechanics researcher so far, and they missed to find the experimental systems that are partially miscible at room temperature and atmospheric pressure."

The research team succeeded in changing the miscibility of the system to fully miscible, immiscible, and partially miscible with little change in the viscosities of high-viscosity or low-viscosity liquids at room temperature and atmospheric pressure by using an aqueous two-phase system consisting of polyethylene-glycol (PEG), sodium-sulfate, and water and by changing the salt (sodium-sulfate) concentration (see Fig. (a)). "We found that a new interfacial deformation is observed in the case where the two liquids are partially miscible (see Fig. (c)) when a more-viscous liquid displaces a less-viscous one in a Hele-Shaw cell (Fig. (b)) which is a model mimics flow in porous media. This is very much counter-intuitive because no deformation takes place in such situation when the two fluids are fully miscible or immiscible (Fig. (b)). We showed this interfacial instability originates due to spontaneous flow driven by phase separation between the soluble species", Nagatsu explains.

"Our result shows that the effect of partial miscibility of liquids on interfacial hydrodynamics is not in the middle of fully miscible and immiscible, but has completely different properties. We emphasize that this will open a new cross-disciplinary research area involving hydrodynamics and chemical thermodynamics. Also, the displacement with partial miscibility in a porous medium takes places in the oil recovery process from the formation and the CO2 injection process into the formation, and thus our finding is expected to contribute to improve the accuracy of the phenomena prediction of those processes, adds Nagatsu.

Credit: 
Tokyo University of Agriculture and Technology

Making sense of flexible sensor systems

image: Imperceptible magnetic sensor matrix system

Image: 
Osaka University

A team of researchers from Osaka University and Leibniz Institute for Solid State and Materials Research developed the world's thinnest and lightest magnetic sensor matrix sheet system that visualizes the two-dimensional distribution of magnetism on various surfaces.

Conventional magnetic sensor circuits consist of silicon-based hard electronic elements integrated on a substrate with a hardness similar to that of glass, meaning they can be only placed on flat surfaces.

Conversely, flexible soft magnetic sensors have also been developed, but there is no device integrating a driving circuit, sensor scanning mechanism, signal processing circuit, and wireless measurement unit, all of which are required to form a system. "This is because the fabrication of a flexible magnetic sensor element is difficult. Furthermore, it is hard to integrate the fabrication process with circuit technology," explains lead author Masaya Kondo.

Now, this joint research team has developed a thin and soft ("skin-like") magnetic sensor matrix sheet system by integrating flexible electronic elements called organic transistors and giant magnetoresistive elements on a 1.5-μm-thick plastic film. This imperceptible circuit fabricated on a thin plastic film can be attached onto the skin of a person without causing discomfort and can function properly even when folded (Fig. 1).

The magnetic sensor matrix sheet system, with a sensitivity ten times higher than that of conventional systems, not only detects and amplifies weak magnetic signals, but also visualizes the two-dimensional distribution of magnetism in real time by automatically scanning magnetic sensor elements arranged in a matrix pattern (Fig. 2).

Among physical information, magnetic information obtained via a two-dimensional sheet-type magnetic sensor system is much more precise than electrical information because magnetic sensors have high spatial resolution due to the high permeability of magnetism in substances. A sheet-type sensor provides high-precision physical information as it can be adhered to a variety of objects regardless of shape.

"Attaching our sheet-type sensor to a reinforced structure identifies the precise locations of damage by mapping the distortion of magnetism caused by deteriorated reinforcing steel bars. Also, once the sensitivity of the sensor is improved further, higher precision cardiac diagnosis will be achieved by magnetic mapping than by conventional electrocardiography," says Prof. Sekitani, who led the study.

Credit: 
Osaka University