Culture

CHAPEL HILL -- The five-year survival rate for adolescents and young adults with cancer has significantly improved from 1975 to 2005 in the United States overall, but this was not the case for all cancers, according to a report in the Journal of the National Cancer Institute.

"We are making improvements in survival for adolescents and young adults with cancer over time, but adolescents and young adults are a heterogeneous group, and we have to make sure that overall improvements don't hide the fact that there are specific cancer types that haven't had equivalent advances, and we need to do more," said Hazel B. Nichols, PhD, member of the University of North Carolina Lineberger Comprehensive Cancer Center and associate professor in the UNC Gillings School of Global Public Health.

Chelsea Anderson, PhD, MPH, postdoctoral fellow at the American Cancer Society, was the study's corresponding author.

The researchers identified substantial improvements in five-year mortality rates for adolescents and young adults (AYA) diagnosed with leukemia, non-Hodgkin lymphoma, Hodgkin lymphoma, central nervous system tumors, melanoma and other skin cancers, breast cancer or kidney cancer.

However, five-year mortality rates for AYA patients with bone tumors, soft tissue sarcomas, bladder cancer, cervical and uterine cancers or colorectal cancer did not improve across the more than 30-year time period.

Researchers compared mortality rates in the five to 10 years beyond diagnosis for people ages 15 to 39. They compared mortality rates for young people in the U.S. who were first diagnosed between 1975 and 1984 with rates for people diagnosed in more recent time periods, including from 1985-1994, 1995-2004 and 2005-2011. The study drew on data from the National Cancer Institute's Surveillance, Epidemiology and End Results database.

They found that all-cause mortality rates in the five to 10 years after diagnosis fell from 8.3 to 5.4 percent between 1975-1984 and 2005-2011. That decline was driven by a drop in the number of deaths from the patients' primary cancer, Nichols said, although deaths from other causes declined as well.

"Some of the most dramatic improvements were for leukemia and non-Hodgkin lymphoma," Nichols said. "In those groups, we saw that if you were diagnosed with leukemia, for example, in 1975, the mortality between five and 10 years was almost 30 percent. If you were diagnosed with that same disease in 2005, the mortality rate was only 7 percent. That's pretty dramatic over a 30-year interval."

UNC Lineberger's Andrew B. Smitherman, MD, MSc, assistant professor and medical director of the UNC Adolescent and Young Adult Oncology Program, said the results were encouraging.

"With improved cancer-directed therapies and enhanced supportive care, survival outcomes are improving among many AYA cancers, including for leukemia, lymphoma and central nervous system cancers," Smitherman said. "Also, improvements in non-cancer mortality were observed that speak to refinements in cancer treatment to limit treatment-related late effects, such as cardiopulmonary disease. The authors also report small decreases in mortality related to secondary cancers. More time will be needed to fully understand how changes in therapy over the past few decades will impact rates of secondary cancers, as these may develop much later."

However, while mortality rates improved overall, there was no major improvement in five-year mortality rates for AYA patients with bone tumors, soft tissue sarcomas, bladder cancer, cervical and uterine cancers, or colorectal cancer.

"This highlights areas where more work needs to be done," Nichols said.

Cancers among adolescents and young adults make up only about 4 percent of all cancers diagnosed in the U.S., researchers reported. However, previous studies indicated that survival improvement has been less dramatic in this age group.

"Cancer risk is still very low overall before 40," Nichols said. "However, we haven't seen strong representation of adolescents and young adults in clinical trials, which may be contributing to the fact that patients with certain cancer types in this age group haven't made big advancements over this time period."

To improve outcomes and provide support for adolescents and young adults, UNC Lineberger and the North Carolina Cancer Hospital launched a program for patients with cancer between the ages of 13 and 40.

The program, which is under the direction of Smitherman and Lauren Lux, LCSW, is designed to recognize that teenagers and young adults have unique cancer biology and have different needs than other patients. Cancer treatment can impact relationships, career, independence, fertility and other aspects of life.

"This study underscores the importance of clinical trials in advancing cutting-edge treatments and cures for cancer," Smitherman said. "Many of the improvements that have been seen in pediatric, adolescent and young adult cancers are due to the work of cooperative research groups. More work is needed to develop new treatments for the AYA cancers that are not seeing equivalent survival improvements. These results can help inform clinical researchers regarding where we need to focus energy to develop new trials, and hopefully improve outcomes."

CHAMPAIGN, Ill. -- A study that relied on citizen scientists to monitor the health of corals on Turks and Caicos Islands in the Caribbean from 2012 to 2018 found that 35 key coral species remained resilient during a 2014-17 global coral-bleaching event that harmed coral reefs around the world. Even corals that experienced bleaching quickly recovered, the researchers found. Some corals appeared healthier in 2017 than they were in 2014.

The researchers report their findings in the Springer Nature journal Applied Sciences.

"Boulder-type corals on the Turks and Caicos Islands demonstrated no significant bleaching as a result of the peak thermal stress in late 2015," said Abby Knipp, who conducted the research while an undergraduate student at the University of Illinois at Urbana-Champaign. Knipp is the first author of a paper detailing the findings. "Plate-type corals did suffer bleaching, but they quickly rebounded. Their pigmentation levels were back to normal within months of the anomalously high thermal stress."

Coral bleaching is a common response to extreme heat stress, and global coral-bleaching events are becoming more frequent as the oceans warm. The 2014-17 bleaching event occurred as record-breaking sea-surface temperatures pushed some corals past their physiological limits. Scientists call it "the most severe, widespread and longest-lasting" global coral-bleaching event on record.

Pigmentation in corals comes from photosynthetic algae, on which the corals depend for nutrients, said U. of I. geology professor and study co-author J. Cory Pettijohn.

"The algae colonize the corals and feed on the byproducts of their metabolism," he said. "When sea-surface temperatures are too high, corals will expel the algae. Corals that experience prolonged bleaching usually die, leaving only a white calcium-carbonate skeleton behind."

In Turks and Caicos Islands, pigmentation of the boulder corals was darker in 2017 than in 2014, suggesting these corals were even healthier after rebounding from the heat stress, Knipp said.

"We were surprised that apparent healing and darkening could happen so fast," she said.

The scientists say more studies are needed to explain the unusual hardiness of the corals at Turks and Caicos Islands, but previous research offers clues to factors that promote coral health. For example, some algal types appear to confer added resilience to corals experiencing heat stress. Ocean salinity and acidity likely play a role. Turks and Caicos Islands tend to have lower water temperatures than other, more thermally stressed regions of the Caribbean. And the massive 2017 hurricanes Irma and Maria cooled surface waters and likely contributed to the corals' recovery, the researchers said.

SEATTLE – Seeing a physician or other health specialist for low back and neck pain? You’re not alone, according to a new scientific study.

Americans in 2016 spent an estimated $380 billion on low back and neck pain, as well as on joint and limb pain, and other musculoskeletal disorders.

In total, $3.1 trillion – or $9,655 per person, about 17.9% of the US GDP – was spent on health care by a combination of individuals and public and private insurance. In 1996, that percentage was 13.3% of GDP, with a total amount of $1.4 trillion, or $5,259 per person.

“The vast costs associated with health care represent one of the most important and contentious issues facing Americans today,” said Dr. Joseph Dieleman of the Institute for Health Metrics and Evaluation (IHME) at the University of Washington’s School of Medicine and lead author of the study. “Our study provides comprehensive estimates over a 20-year period that highlight how health care and prescription drugs are paid for, what they are spent on, and how such payments have changed over time.”

Among 154 conditions included in today’s study, low back and neck pain generated the highest expenditures at $134.5 billion. When combined with all other musculoskeletal disorders, such as joint and limb pain, osteoarthritis, and rheumatoid arthritis, the total exceeds $380 billion, or 14.1% of the $2.7 trillion included in this study for 2016.

Other health conditions with substantial spending in 2016 were diabetes ($111.2 billion), ischemic heart disease ($89.3 billion), and falls ($87.4 billion).

As expected, a combination of private and public insurance paid for the majority of those expenditures:

Low back and neck pain – $76.9 billion paid by private insurance, $45.2 billion paid by public insurance, and $12.3 billion paid by individuals out-of-pocket

Other musculoskeletal disorders – $73.3 billion paid by private insurance, $46.9 billion paid by public insurance, and $9.7 billion paid by individuals out-of-pocket

Diabetes – $55.4 billion paid by public insurance; $49.1 billion paid by private insurance, and $6.7 billion paid by individuals out-of-pocket

Ischemic heart disease – $48.2 billion paid by public insurance, $37.9 billion paid by private insurance, and $3.2 billion paid by individuals out-of-pocket

Falls – $40.7 billion paid by public insurance, $34.8 billion paid by private insurance, and $11.9 billion paid by individuals out-of-pocket

The majority of public insurance spending (58.6%) in 2016 was earmarked for patients aged 65 or older. After adjusting for changes in the population size and age, spending by public insurance increased faster than private insurance, although this is driven at least partially by expansions of Medicaid.

Other findings include:

Spending in 2016 on prescription pharmaceuticals totaled $336.0 billion, with 45.4% paid by private insurance; spending by public insurance has increased from 19.1% in 1996 to 40.6% in 2016, with an increase in 2006 associated with Medicare Part D.

Spending on dementia increased substantially, from $38.6 billion in 1996 to $79.2 billion in 2016.

Data behind the study included 5.9 billion unique insurance claims, information regarding an additional 150.4 million ambulatory care visits, dental procedures, and emergency department visits; 1.5 billion inpatient and nursing facility bed-days; and 5.9 million prescribed pharmaceuticals.

The spread of antibiotic resistance is partly due to the ability of bacteria to pick up DNA from their surroundings. A new study, which started at the University of Groningen, showed that drugs blocking this ability (which is called 'competence') in the bacterium Streptococcus pneumoniae can indeed stop the spread of resistance in mice. As competence is blocked without affecting cell growth, it will be difficult for the bacteria to evolve resistance to the blockade. The study was published online by the journal Cell Host & Microbe on 3 March.

The bacterium Streptococcus pneumoniae is often present in our nose or throat and is usually harmless. However, it can migrate to other parts of the body, causing severe diseases. The only way to treat these infections is with antibiotics, but with this treatment, acquisition of antibiotic resistance is a cause for concern. In order to pick up these resistance genes, a chain of events is needed that brings the bacteria in a state called 'competence'. During competence, bacteria express all the machinery required to 'catch' and incorporate the resistance genes into their own genomes.

Growth stress

In a project that started at the University of Groningen in the Netherlands and was finished at the Swiss University of Lausanne, Arnau Domenech and colleagues figured out how to stop the cells from becoming competent. 'We collaborated with scientists from Heidelberg, who developed a high-throughput assay to simultaneously test cells for competence and growth,' says Domenech. In this assay, 1366 approved drugs were screened. It turned out that 46 of them blocked the induction of competence, without negatively affecting growth.

'When cells are under growth stress, for instance in the presence of antibiotics, they try to find a solution and become resistant to these drugs,' explains Domenech. 'Importantly, we did not observe resistance to the drugs found here as they do not cause growth stress.' The 46 drugs could be divided into two groups: drugs affecting ion homeostasis, and antipsychotics. Several candidates were selected for further exploration. 'This showed that they all acted through the same mechanism,' says Domenech. They disrupted the proton-motive force: the electrochemical gradient that moves protons across the bacterial membrane and powers various processes.

Resistance

'The result is that the cells fail to secrete a peptide called CSP,' explains Domenech. The CSP concentration outside the cells induces competence through a process called quorum sensing: if enough cells secrete CSP, the concentration will reach a threshold that activates competence genes.

Domenech: 'In the lab, we observed that our competence-blocking drugs could prevent the transfer of antibiotic resistance genes to susceptible strains of Streptococcus pneumoniae and we obtained the same results in cultures of human lung epithelial cells.' The drugs also reduced the transmission of bacterial resistance genes in a mouse model of infection.

Antibiotics

The concentrations blocking the induction of competence were lower than those inhibiting growth. However, they may still not be safe to treat patients, as human cells also rely on the proton-motive force for some vital functions. 'Nevertheless, we discovered a general pathway that we can block to prevent the spread of antibiotic resistance,' says Domenech. Future studies must show whether it is feasible to use this approach in humans. If that is the case, the finding could be a breakthrough: competence blockers are anti-evolution drugs, which could be given together with antibiotics. This combination would be a very powerful weapon in the fight against infections and could extend the lifespan of current antibiotics.

An explanimation of the study can be found on YouTube: https://youtu.be/WlAoEbNcOFY

What The Study Did: Data from annual financial reports were used to compare the profitability of 35 large pharmaceutical companies with 357 companies in the S&P 500 Index from 2000 to 2018. This study is part of a theme issue from JAMA on drug pricing.

Authors: Fred D. Ledley, of Bentley University in Waltham, Massachusetts, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jama.2020.0442)

Editor's Note: The article includes funding/support disclosures. Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

What The Study Did: Researchers estimated the cost to bring 63 new drugs or biologics to market between 2009 and 2018 using publicly available data on research and development expenditures for these medicines. This study is part of a theme issue from JAMA on drug pricing.

Authors: Olivier J. Wouters, Ph.D., of the London School of Economics and Political Science, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jama.2020.1166)

Editor's Note: The article includes conflict of interest disclosures. Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

What The Study Did: This study describes changes in list and net prices for 600 branded drugs in the U.S. from 2007 to 2018 and estimated the extent to which price increases were offset by increases in discounts. This study is part of a theme issue from JAMA on drug pricing.

Authors: Inmaculada Hernandez, Pharm.D., Ph.D. of the University of Pittsburgh School of Pharmacy, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jama.2020.1012)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

Large pharmaceutical companies are more profitable than most companies in the S&P 500 according to a study published in the Journal of the American Medical Association (JAMA) titled "Profitability of Large Pharmaceutical Companies Compared with Other Large Public Companies." Pharmaceutical profits were closer to those of other research-based companies within the S&P 500 and were not higher than companies in the technology sector.

The study from the Center for Integration of Science and Industry at Bentley University is the first to critically examine the profitability of the companies that are responsible for the development, manufacturing, marketing and sale of most medicines. The results may inform policies to ensure both the affordability and availability of essential medicines now and in the future.

The study was undertaken in the context of public opinion surveys showing that 80% of respondents believe the profits made by pharmaceutical companies are a major factor contributing to the price of prescription drugs. "While there is extensive research on the health impacts of unaffordable drugs, there has been little research on the profitability of pharmaceutical companies," said Dr. Fred Ledley, director of the Center for Integration of Science and Industry, and the senior author of the study. "Developing policies to assure the affordability of essential medicines will also require an understanding of how reducing drug prices may impact the industry that makes these drugs available."

The Bentley University study compared the profits of 35 large pharmaceutical companies with those of 347 companies from the S&P 500 Index. During the period from 2000 through 2018, the pharmaceutical companies had a cumulative revenue of $11.5 trillion and cumulative net income of $1.9 trillion. Net income, also called "earnings," reflects the difference between all revenues and expenses and is a company's "bottom line" used in calculating earnings per share. Over this same period, the median net income margin (the percentage of revenue remaining after deducting all expenses) for pharmaceutical companies was 13.7% compared to 7.7% for S&P 500 companies, a difference of 6.1%. However, when comparing pharmaceutical companies to those S&P 500 companies reporting research and development expenses and considering the effects of company size and time trends, the difference in median profits was 3.6%, and pharmaceutical companies were not more profitable than those companies in the technology sector or healthcare companies developing non-pharmaceutical products. Over the past five years, from 2014-2018, there was no significant difference in net income margin between pharmaceutical and S&P 500 companies.

These estimates of pharmaceutical profit margins were lower than those used by the National Academies of Science in their 2017 report, Making Medicines Affordable: a National Imperative.

The Bentley study focused explicitly on large pharmaceutical companies, which provide the large majority of all medicines. In 2018, these companies had a combined market value of $2.4 trillion, directly employed 992 thousand people, and expensed $120 billion for research & development of new medicines. Pharmaceutical companies represent only one element of the pharmaceutical distribution system, which also includes pharmacy benefit managers, wholesalers, pharmacies, and healthcare providers as well as academic laboratories and biotechnology companies involved in basic and applied research leading to the development of new medicines.

What The Study Did: What the pharmaceutical and health product industry spent on lobbying and contributions to political campaigns in the U.S. from 1999 to 2018 was the focus of this observational study that used federal- and state-level data. This study is part of a theme issue from JAMA on drug pricing.

Author: Olivier J. Wouters, Ph.D., of the London School of Economics and Political Science, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamainternmed.2020.0146)

Editor's Note: Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

What The Study Did: A variety of data were used to estimate annual health care spending in the U.S. from 1996 through 2016 by payer (public insurance, private insurance and out-of-pocket payments) and by health conditions, including low back pain and musculoskeletal disorders, diabetes and ischemic heart disease. This study is part of a theme issue from JAMA on drug pricing.

Authors: Joseph L. Dieleman, Ph.D., of the Institute for Health Metrics and Evaluation in Seattle, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jama.2020.0734)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

You just finished a good meal and are feeling full? Researchers from the CNRS, Inrae, University of Burgundy, Université de Paris, Inserm, and University of Luxembourg (1) have just revealed the mechanisms in our brains that lead to this state. They involve a series of reactions triggered by a rise in blood glucose levels. This study, which was conducted on mice, is published in Cell Reports on 3 March 2020.

The neuronal circuits in our brain governing feelings of hunger and satiety can modify their connections, thereby adjusting feeding behaviour to living conditions and maintaining a balance between food intake and calorie expenditure. Scientists suspect that this plasticity could be altered for obese subjects.

In a new study conducted on mice, a team led by Alexandre Benani, a CNRS researcher at the Centre for Taste and Feeding Behavior (CNRS/Inrae/University of Burgundy/AgroSup Dijon), has shown that these circuits are activated on the time scale of a meal, subsequently regulating feeding behaviour. However, this activation does not occur through a change in the circuit's "connections."

Scientists focused on POMC neurons in the hypothalamus, located at the base of the brain, which are known for limiting food intake. They are connected to a large number of neurons from other parts of the brain, with the connections of this circuit being malleable: they can be made and unmade very quickly based on hormonal fluctuations. Researchers observed that this neuronal circuit is not modified after a balanced meal, but that other nerve cells associated with POMC neurons, known as astrocytes, actually change form.

Astrocytes are star-shaped nerve cells that were first studied for their supporting role with respect to neurons. Under usual conditions, they sheathe POMC neurons and act somewhat like brake pads by limiting their activity. After a meal, blood glucose levels (glycaemia) temporarily increase, with astrocytes detecting this signal and retracting in less than one hour: once this "brake" is released, POMC neurons are activated, ultimately promoting the feeling of satiety.

Surprisingly, a meal that is high in fats does not lead to this remodelling. Does this mean that lipids are less effective in satisfying hunger? The scientists are trying to determine whether they trigger satiety through another circuit. It also remains to be seen whether sweeteners have the same effects, or whether they lure the brain by providing an addictive sensation of sweetness without satisfying hunger.

The historic economies of Mongolia are among the least understood of any region in the world. The region's persistent, extreme winds whisk away signs of human activity and prevent the buildup of sediment which archaeologists rely on to preserve the past. Today crop cultivation comprises only a small percent of Mongolia's food production, and many scholars have argued that Mongolia presents a unique example of dense human populations and hierarchical political systems forming without intensive farming or stockpiling grains.

The current study, led by Dr. Shevan Wilkin of the Max Planck Institute for the Science of Human History provides, for the first time, a detailed glimpse into the diets and lives of ancient Mongolians, underscoring the importance of millets during the formation of the earliest empires on the steppe.

Isotopic analysis and the imperial importance of millets

Collaborating with archaeologists from the National University of Mongolia and the Institute of Archaeology in Ulaanbaatar, Dr. Wilkin and her colleagues from the MPI SHH sampled portions of teeth and rib bones from 137 previously excavated individuals. The skeletal fragments were brought back to the ancient isotope lab in Jena, Germany, where researchers extracted bone collagen and dental enamel to examine the ratios of stable nitrogen and carbon isotopes within. With these ratios in hand, scientists were able to reconstruct the diets of people who lived, ate, and died hundreds to thousands of years ago.

Researchers tracked the trends in diet through the millennia, creating a "dietscape" which clearly showed significant differences between the diets of Bronze Age peoples and those who lived during the Xiongnu and Mongol Empires. A typical Bronze Age Mongolian diet was based on milk and meat, and was likely supplemented with small amounts of naturally available plants. Later, during the Xiongnu Empire, human populations displayed a larger range of carbon values, showing that some people remained on the diet common in the Bronze Age, but that many others consumed a high amount of millet-based foods. Interestingly, those living near the imperial heartlands appear to have been consuming more millet-based foods than those further afield, which suggests imperial support for agricultural efforts in the more central political regions. The study also shows an increase in grain consumption and increasing dietary diversity through time, leading up to the well-known Mongolian Empire of the Khans.

Rethinking Mongolian prehistory

The new discoveries presented in this paper show that the development of the earliest empires in Mongolia, like in other parts of the world, was tied to a diverse economy that included the local or regional production of grain. Dr. Bryan K. Miller, a co-author who studies the historical and archaeological records of Inner Asian empires, remarks that "these regimes were like most empires, in that they directed intricate political networks and sought to amass a stable surplus - in this case a primarily pastoral one that was augmented by other resources like millet."

"In this regard," Dr. Miller adds, "this study brings us one step closer to understanding the cultural processes that led humanity into the modern world."

The view that everyone in Mongolian history was a nomadic herder has skewed discussions concerning social development in this part of the world. Dr. Wilkin notes that "setting aside our preconceived ideas of what prehistory looked like and examining the archaeological record with modern scientific approaches is forcing us to rewrite entire sections of humanity's past." Dr. Spengler, the director of the archaeobotany labs at the MPI SHH, emphasizes the importance of this discovery, noting that "this study pulls the veil of myth and lore off of the real people who lived in Mongolia millennia ago and lets us peak into their lives."

Oxytocin is known for its role in childbirth and breastfeeding and it has also been shown to have a wider application in the development and regulation of social behaviour in many species. There has been increasing interest in its potential use to help people overcome social difficulties as this can be one of the most difficult symptoms to treat in many psychiatric conditions such as schizophrenia, autism, anxiety and depression.

Research into the use of oxytocin almost always uses nasal spray application but little is known about how well this method delivers the required dose and reaches different areas of the brain.

Published in Nature Communications, the study is the first to compare different routes and administrations of synthetic oxytocin in terms of how they affect regional blood flow in the human brain, a surrogate measure of neuronal activation, as measured using fMRI scans.

Researchers compared three different methods in a sample of 17 male participants: injection of oxytocin into the blood; administration of oxytocin with a standard nasal spray; and administration with a nebuliser. The nebuliser, a special nasal delivery device which administered a fine spray of oxytocin in a pulsatile fashion, was investigated as it is thought it can better reach important parts of the nasal cavity.

The results showed that, compared to when no oxytocin is delivered, both the intravenous and the nasal route of administering oxytocin reduced regional blood flow to the amygdala which is a key brain area involved in processing of social information, emotion and social anxiety.

Researchers also showed that the nasal route targeted other specific brain areas and that the patterns of regional blood flow differed depending on whether oxytocin was delivered through a standard spray or the nebuliser.

Senior author, Yannis Paloyelis from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) King's College London said: 'Our results show that a one-size-fits-all approach to administrating oxytocin is not the best approach and, to a certain extent, it may be possible to target where in the brain it takes effect.

'This has important implications for the potential application of oxytocin to patients as it suggests that, for some disorders, one route or mode of administration may be superior to others. For example, clinical applications aiming to target the frontal gyrus, insula or parts of the basal ganglia may achieve better results using the nasal route. Nevertheless applications that increase the amount of synthetic oxytocin in the blood, such as intravenous administration, could still have an application, as they can achieve localised effects in, for example, the amygdala or the anterior cingulate cortex and allow precise control over the administered dose. This could be very useful for future clinical trials.'

The researchers highlighted that the research might also be relevant for a range of compounds used in the treatment of neuropsychiatric and other disorders, for example nasal administration has been identified as an important route for delivery of insulin and ketamine. More research is needed to provide a more detailed insight into which brain areas are better targeted by nasal delivery and how this can be better optimised.

WASHINGTON, March 3, 2020 -- Recent advances in bioengineering and computational modeling have given researchers the ability to examine complex biological processes with molecular-level detail.

A review of recent work in biophysics highlights efforts in cellular engineering, ranging from proteins to cellular components to tissues grown on next-generation chips. Author Ngan Huang said the fast pace of development prompted her and her colleagues to take stock of promising areas in the field as well as hurdles researchers can expect in coming years. They discuss their work in this week's APL Bioengineering, from AIP Publishing.

"What excites me most is the multidisciplinary nature of the field. It brings together researchers of diverse expertise, including biophysics, biomaterials, molecular biology, chemical and systems biology, computational biology and developmental biology," she said. "As more diverse expertise is applied to this field in the future, we anticipate even more advancements will be made."

Advances in understanding the cellular microenvironment led to new mechanical properties for researchers to explore. Viscoelasticity and viscoplasticity describe how materials deform when a stress is applied to them and how well they keep their shape, an understanding that has shown how cells respond when they encounter one another and how they move through tight spaces.

At the molecular level, new techniques, such as fluorescence resonance energy transfer, make it possible for researchers to see and better study the effects intrinsically disordered proteins (IDPs) have on physical properties of cells. IDPs lack a rigid shape and have been recently found to control cellular function by altering phase transitions within cells.

Engineered synthetic proteins also emerged as a hotbed of bioengineering research in recent years, finding use in tracking enzymes bound to cell membranes and making up a key component of many emerging cancer immunotherapies.

Development of increasingly powerful computational tools to better model molecular behaviors has allowed researchers to better predict how IDPs change shape and how synthetic proteins are likely to fold. These tools have already helped researchers create easy-to-use chips that replicate how specific biological tissues behave.

Organ-on-a-chip technology looks to provide a high-resolution, high-throughput method for researchers to investigate how tissues respond to conditions like exposure to experimental drugs. Such approaches might offer faster findings without the use of animal testing.

"In the area of multi-cellular systems, one challenge is the development of organs on a chip that incorporate complex spatial geometries and cell types to allow us to study how different cells interact with one another, while providing high-resolution imaging and high-throughput analysis," Huang said.

She said she hopes the paper inspires students from more disciplines to participate in the field.

Researchers in Simon Fraser University's Brinkman Laboratory are collaborating with U.S. researchers to test a new drug that can kill a wide range of superbugs - including some bacteria now resistant to all common antibiotics.

Known as AB569, the drug contains ethylenediaminetetraacetic acid (commonly referred to as EDTA) and acidified nitrite, two inexpensive chemicals that the researchers discovered work together to effectively kill disease-causing bacteria without harming human cells.

"We have a growing crisis with antibiotics becoming less and less effective, and treatments are failing; that's why it's important to test and develop new drugs and approaches to treat disease-causing bacteria that are highly resistant to existing antibiotics," says Geoff Winsor, lead database developer at SFU's Brinkman Lab, which is headed by SFU professor Fiona Brinkman.

SFU researchers characterized, at the molecular level, how the chemicals in the AB569 compound were likely working together to kill the notoriously drug-resistant Pseudomonas aeruginosa, using their Pseudomonas Genome Database hosted at SFU, and computer-based analyses of molecular data.

Pseudomonas aeruginosa is a type of bacteria that can cause infections in the lungs (pneumonia), urinary tract, or blood. It is known as the leading cause of morbidity in patients with cystic fibrosis. People who are in hospital or have compromised immune systems are particularly at risk of developing an infection caused by this bacteria.

Pseudomonas aeruginosa is categorized by the World Health Organization as a "priority pathogen" of concern. These priority pathogens are highlighted as urgently requiring new treatments, and posing the greatest threat to human health.

The top three priority pathogens include highly drug-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae. The AB569 compound has been shown to kill these bacteria, plus a wide variety of others, including the notoriously difficult to treat Methicillin-resistant Staphylococcus aureus or MRSA.

"AB569 will go through additional testing because it shows potential as non-toxic topical drug treatment for a wide range of infections," says Winsor.

The lab tests of AB569 showed promising results in treating priority pathogens, plus additional bacteria that cause foodborne illness such as E. coli and Listeria.

The AB569 compound was developed by a University of Cincinnati scientist and is now in the first phase of human trials. AB569 has been licensed exclusively to Toronto-based biotechnology firm Arch Biopartners.