Culture

The novel small molecules, based on new target, new chemical structure and new antimicrobial mechanism, are different from those of existing antibiotics. The new drug candidates demonstrate much effective abilities of inhibiting bacterial growth than commonly used antibiotics, yet with no toxicity to human cells.

Drug resistance has been declared as one of the biggest threats to global health in 2019 by the World Health Organization, with MRSA becoming one of the most serious concerns. Hong Kong cannot be spared from the worsening scourge of MRSA. In 2018, there were 1,218 reported cases of community-associated MRSA (CA-MRSA), or a seven-fold of the figure in 2007 - the year the disease became notifiable in Hong Kong. As of August this year, there were already 839 cases reported. Despite of tremendous pharmaceutical research and development investments worldwide, the search for new antibiotics has showed no progress since mid-1980s.

The development of "Nusbiarylins", a new class of antimicrobial agents, by the research team of the State Key Laboratory of Chemical Biology and Drug Discovery of PolyU's Department of Applied Biology and Chemical Technology (ABCT), is thus a breakthrough in the battle against multi-drug resistant bacterial infections. The interdisciplinary team, led by Dr MA Cong, Assistant Professor in ABCT, comprises of experts from both PolyU and Faculty of Medicine of The Chinese University of Hong Kong.

"Our research is now in the stage of animal studies, conducting infectious model studies and pharmacokinetic studies. These are the critical steps preceding clinical trials on human for drug development. At this moment, there are very few antibiotic related studies being able to complete such stage worldwide. Our findings so far are very promising. We believe further studies on these compounds will contribute to a new era of antibiotic discovery, contributing towards the fight against superbugs," said Dr Ma.

New target being identified by innovative antimicrobial mechanism

Most antibiotics currently in the market fight against bacteria through disrupting its DNA synthesis or protein functions. The innovative antimicrobial mechanism developed by PolyU team focuses on inhibiting the interaction between two proteins, NusB and NusE, which is crucial for synthesis of bacterial ribosomal RNA (rRNA). By designing small molecules to disrupt NusB-NusE interaction, bacterial cell proliferation can thus be curbed.

The team developed a model basing on the structure of NusB and NusE, and applied computer-aided screening to screen about 5,000 small molecule compounds with drug-like properties to explore for inhibitors for NusB-NusE interaction. The shortlisted compounds were then put to tests for antimicrobial activity against different MRSA strains. A compound, (E)-2-{[(3-ethynylphenyl)imino]methyl}-4-nitrophenol (hereafter addressed as MC4), was identified as having much effective antibacterial abilities than the commonly used antibiotics. The Minimum Inhibitory Concentration (note: MIC denotes the lowest concentration of a chemical/drug for preventing bacterial growth) of MC4 for some MRSA strains are as low as 8 μg/mL, compared to the MICs of >64 μg/mL demonstrated by two antibiotics in the market, oxacillin and gentamicin.

Test of MC4 on human lung and skin cells (infections caused by MRSA often occur in these tissues) indicated no significant toxicity. The fact that NusB and NusE exist only in bacteria and not human cells has also addressed toxicity concern.

"Nusbiarylins" -- a new class of antibiotic candidates

The research team has further structurally modified MC4 for optimization, and 167 analogues were synthesized so far. The new class of compounds are named as "Nusbiarylins" (basing on their target protein "NusB" and their "biaryl" structure). Laboratory test of Nusbiarylins against a panel of MRSA strains proved their consistent antibacterial activity, some with MIC as low as 0.125 μg/mL, much better than commonly used antibiotics, including vancomycin with the MIC of 1 μg/mL which is labelled as the "last resort" antibiotic drug in the United States.

Further pre-clinical studies on the in vitro pharmacological properties of Nusbiarylins on human cells indicated that the compounds:

leading to nearly no hemolysis (i.e. human blood cell breaking), an indication of being safe for injection; and

with excellent result in intestine absorption, implying being effective for oral taking.

The pathogen Acinetobacter baumannii is one of three highest priority pathogens identified by WHO (World Health Organisation) for which new antibiotics are urgently needed

Understanding the enzymes that assemble antibiotics which can kill the pathogen is key to altering their structures to target the pathogen more effectively

Researchers at the University of Warwick have made a breakthrough in understanding the functions and structures of key enzymes in the assembly of an antibiotic with activity against the pathogen, which could enable more effective versions to be created

One of the WHO's three critical priority pathogens, Acinetobacter baumannii, for which new antibiotics are urgently needed is one step closer to being tackled, as researchers from the Department of Chemistry - University of Warwick have made a breakthrough in understanding the enzymes that assemble the antibiotic enacyloxin.

Acinetobacter baumannii is a pathogen that causes hospital-acquired infections that are very difficult to treat, because they are resistant to most currently available antibiotics.

In a previous paper, researchers at the University of Warwick and Cardiff University showed that a molecule called enacyloxin is effective against Acinetobacter baumannii. However, the molecule needs to be engineered to make it suitable for treating infections caused by the pathogen in humans.

The first step to achieving this is to understand the molecular mechanisms used to assemble enacyloxin by the bacterium that makes it. In their paper 'A dual transacylation mechanism for polyketide synthase chain release in enacyloxin antibiotic biosynthesis' published in the journal Nature Chemistry, the researchers identify the enzymes responsible for joining the two components of the antibiotic together.

The key enzyme in this process was found to be promiscuous, suggesting it could be harnessed to produce structurally modified versions of the antibiotic.

Professor Greg Challis of the Department of Chemistry at the University of Warwick comments:

"Being able to alter the structure of the antibiotic will be key in future studies to optimise it for treating infections in humans."

In a second paper, titled 'Structural basis for chain release from the enacyloxin polyketide synthase' also published in Nature Chemistry, the researchers report the structure of the enzyme and that of a companion protein which plays a key role in the process.

Professor Józef Lewandowski also of the Department of Chemistry at the University of Warwick, who co-led the structural study comments:

"We found how specific parts of the enzyme and the companion protein recognise each other. Using a computer algorithm to search all publicly available bacterial genomes, we learned that these recognition elements are commonly found in other enzymes and proteins that make antibiotics and anti-cancer drugs."

Professor Challis continues:

"Understanding how the enzymes and their companion proteins recognise each other provides important clues about the evolution of antibiotic production in bacteria. It also has the potential to be exploited for creation of new types of molecules not seen in Nature."

When the immune system fends off pathogens, this can happen in a very wide variety of ways. For example, the immune system's memory is able to distinguish a foreign protein with which the organism has already come into contact from another and to react with a corresponding antibody. Researchers have now investigated experimentally whether this ability of the immune system to specifically fend off pathogens can adapt in the course of evolution. To this end, they studied many successive generations of flour beetles - because insects can also specifically repel pathogens to a certain degree.

After the researchers repeatedly confronted the insects and their progeny with bacteria, they observed that the beetles' immune system reacted more strongly after just a few generations. "Our study helps us to understand whether an immune system's specificity ability can adapt quickly to the conditions of repeated confrontation with pathogens," says Prof. Joachim Kurtz from Münster University, who is heading the study.

The results might be able to help provide a better understanding of molecular processes that play a role in the innate immune memory in humans and that could perhaps be used for medical purposes. As insects are well suited for experimental evolution, the information thus acquired could usefully complement existing knowledge on the immune system of mammals. The study has been published in the journal "PNAS" (Proceedings of the National Academy of Sciences).

Background and method:

The immune system in human beings consists of two main systems - the innate immune system and the adaptive one. The latter is the part which primarily "remembers" pathogens and can react specifically. Insects have a different immune system, but researchers have already been able to show that insects too are able to show a greater reaction to infections as a result of previous experience with pathogens. However, it has not yet been investigated whether this immunological specificity can adapt evolutionarily to the respective bacterial environment.

For their experiment, the evolutionary biologists collected data from more than 48,000 red flour beetles over a period of three years. They divided the beetles into different groups in order to expose them to different combinations of six different bacterial species in each case in the larval stage first killed and then living bacteria. In some of the groups, the researchers used the same bacteria within one generation; in the other groups they confronted the beetles with a variety of different bacteria. 14 generations and three years later, they produced the results of the experiment: beetles which had been exposed to the same type of bacteria for "vaccination" and infection had developed a higher specificity over generations. This helped the beetles especially whenever they had to defend themselves against Bacillus thuringiensis, a natural insect pathogen.

The increased specificity was demonstrated by the fact that after "vaccination" with this natural pathogen, a greater activation of certain genes could be detected which play a role for the immune system and metabolism. At the same time, the survival chances of the beetles rose after being infected with the bacterium - in contrast to beetles that had evolved towards a low specificity. "This means that for certain bacteria a high specificity can develop quickly during evolution - probably caused by changes in the immune genes," say the lead authors, Dr. Kevin Ferro and Dr. Robert Peuß, who carried out the experiments as part of their PhDs at the Institute of Evolution and Biodiversity at Münster University. It was noticeable, however, that this change did not occur in all bacteria used in the experiment. One possible explanation for this might be the limited opportunities of insects to recognize and combat various antigens.

Relevance and prospects:

The molecular mechanisms identified in this experiment could be relevant for humans - in so-called 'trained immunity', a possibility being discussed in medicine for training the memory not only of the acquired, but also of the innate part of the immune system. Based on the newly acquired genetic data, the researchers want to take a more precise look at the immune memory of insects and "deactivate" the relevant genes using molecular-biological methods. In future, the researchers also want to examine the bacteria to see whether for example they develop faster when their host is prepared for them. As flour beetles are seen as a pest in food production, among others, the researchers' results could help to find a new strategy to combat them.

Cooperation in mutual competition is a basic mechanism for the prosperity of human society. However, the simplest model of cooperation in game theory predicts that cooperation will not emerge among rational people because cooperative behaviors incur costs to cooperators, and free riding is a better option.

The team analyzed what strategy can promote and maintain a cooperative society in a basic model of a social dilemma called "the prisoner's dilemma" by introducing a new action of not participating in games. While previous studies could only analyze simple combinations of strategies, the research team used agent simulations and developed a method for visualizing more complex simulation results, enabling the research team to analyze adaptive strategies in an environment where approximately 20,000 strategies coexist and compete with each other.

They determined a strategy that can lead to mutual cooperation without using non-cooperative actions even when facing an exploiter. The strategy can be described as "escape interaction if a partner defected or cooperate if a partner escaped interaction".

Yamamoto says that cooperative society can be maintained without using the action of revenge if the action of escape is possible, and this may expand the research on the evolution of cooperation.

Cancer researchers from the University of Bath have identified some promising drug candidates by using high-throughput screening methods to test tens of thousands of molecules.

The research team from the Departments of Pharmacy & Pharmacology and Chemistry are studying a protein called α-methylacyl-CoA racemase (AMACR) as a potential target for cancer treatments. Levels of AMACR protein and activity are increased by ~10-fold in all prostate cancers. Experiments have shown that reducing these levels makes cancer cells less aggressive, and their behaviour reverts to more like normal cells.

In this study the team tested more than 20,000 drug-like molecules for inhibition of AMACR using a method developed at the University of Bath. This approach, using a simple colour-change technique, allows rapid assessment of the active compounds and identification of new types of drug. The researchers identified drugs which effectively inhibit AMACR in a different way to those that have previously been developed.

The study is published in the journal Bioorganic Chemistry.

Lead author Dr Matthew Lloyd said: "Although previously identified drugs are very effective in laboratory tests, in practice they are difficult to use in therapies because their properties do not allow easy distribution throughout the body. We started this study because we wanted to identify drugs which would be easier to use therapeutically. Although the particular compounds identified in this study did not kill prostate cancer cells very effectively, it is very promising that drug-like molecules were identified."

The study was funded by Prostate Cancer UK with support from the Movember Foundation as part of their initiative to develop new treatments for prostate cancer. A large proportion of the study was performed by first author Yoana Petrova, during the summer of 2015 whilst she was a Pharmacy undergraduate at the University of Bath. This placement was undertaken as part of the Biochemical Society Summer Vacation Studentship scheme. Yoana graduated from the Department of Pharmacy & Pharmacology in the summer of 2016 and is now undertaking a PhD.

Simon Grieveson, Head of Research Funding at Prostate Cancer UK said: "With one man dying from prostate cancer every 45 minutes in the UK there is a desperate need to develop new and effective treatments for the disease, and that's why it's so important that we continue to fund explorative studies like this. The protein AMACR has been shown to be present in larger quantities in aggressive prostate cancer cells, and this research group have successfully developed a technique to find the protein and monitor its activity. Further to this, they have now found certain compounds that can target this protein's activity in the lab, and stop the cancer cells in their tracks. The research is still in its infancy and is some way off from clinical investigation, however this is certainly promising and we look forward to seeing how this research progresses over the coming years."

In the United Kingdom, prostate cancer is the most common male-specific cancer with 47,151 new diagnoses reported in 2015 and 11,287 deaths in 2014. It accounts for 26% of all cancers diagnosed in men, with one in eight men being diagnosed with prostate cancer in their lifetime. Although 84% of men will survive for at least 10 years with the disease, new treatments are urgently needed especially for those men diagnosed with more advanced disease.

With the aid of highly advanced microscopes and synchrotron sources, researchers from the University of Copenhagen have gained seminal insight into how bacteria function as defence mechanisms against attacks from other bacteria and viruses.

The study, which has just been published in the renowned journal, Nature Communications, also describes how the defence systems can be activated on cue. This discovery can turn out to be an important cornerstone in fighting diseases in the future.

The researchers have shown how a cell attacked by a virus activates a molecule called COA (Cyclic Oligoadenylate), which in turn activates a so-called protein complex called CSX1 to eradicate the attacker.

'Expressed in popular terms, the CSX1 starts cutting up the intruder. We can see how CSX1 is activated, rotates and starts defending the cell, once COA is activated,' Professor Guillermo Montoya from Novo Nordisk Foundation Center for Protein Research at the Faculty of Health and Medical Science explains.

Can help fight disease

The researchers at the University of Copenhagen have also managed to successfully activate the process themselves. They sent a COA molecule after the protein complex, so to say, and thus started the defence mechanism.

'In short, we have found a switch that turns on the cell's defence system when we want it to, and so we can diffuse possible attacks,' Guillermo Montoya elaborates.

It is the first time ever that researchers have managed to map and activate a bacterial immune system.

'A few years ago, science wasn't even aware that bacteria had some sort of immune defence system. With this discovery, we have come a great deal further in terms of understanding these mechanisms,' Guillermo Montoya says.

Furthermore, the discovery is interesting because the defence system in bacteria resemble in many ways the human innate immune system.

'Therefore, it is also a step along the way of understanding the human immune system better as well as knowing how to fight bacteria and defend oneself against viruses and in the long run even multiple resistance,' Guillermo Montoya says.

Minimal molecules and a huge magnifying glass

The discovery of a bacteria defence system was made possible by using so-called x-ray crystallography at an establishment in Switzerland and one of the world's most powerful microscopes - the so-called synchrotron MAX IV - in Lund, Sweden.

The image of the CSX1protein complex was made possible by the advanced cryogenic electron microscope at the University of Copenhagen's high tech CryoEM facility - in popular terms a strong magnifying glass.

'CSX1 is approximately 0.00005 mm long. This equates cutting one millimetre into 10,000 slices and then placing five pieces on top of each other. We have taken the pictures one by one and made a short film that reveals the activity inside CSX1,' Guillermo Montoya explains.

Job sharing offers a route to increase the number of women in senior leadership roles in higher education.

Research from Lancaster University Management School, published in a special issue of Social Sciences, shows the potential for job sharing to provide new routes into senior management positions and to increase female presence in the upper echelons of the sector.

Despite recent increases, only 27 per cent of Chairs of Governing bodies in UK higher education are women, similarly the proportion of female Vice-Chancellors also standing at 27 per cent. The number of women leading academic faculties or schools has not grown since 2016.

One reason behind the lack of senior women leaders is the proportion of female professors, with 26 per cent being female in the UK - and similar numbers across Europe - in 2017/18. With a previous career in research and a professorial appointment a pre-requisite for a Vice-Chancellor appointment, this limits the number of potential candidates.

However, the researchers found that job sharing offered the opportunity to open up the talent pipeline, increasing the number of potential candidates for higher-level posts.

"There is a scarcity of female leadership representation in higher education," said report co-author Emma Watton, Director of the Executive MBA at Lancaster University. "In particular, there is a problem in the development of a future leadership pipeline.

"The culture of long working hours, job uncertainty and recent financial constraints across the sector, with multiple reorganisations at HE establishments, together with often an entrenched male leadership community, mean sometimes women make a decision not to apply for senior leadership roles.

"Job sharing enables women - and men - to remain in or be recruited to senior management roles where greater working flexibility is valued, for example to accommodate caring responsibilities or whilst studying part-time.

"We believe that leadership job sharing is a useful and practical method for retaining female talent and skills, and broadening the pipeline of future leaders. By organisations actively endorsing the vast majority of posts as suitable for job sharing, we strongly believe there would be a positive impact on the female leadership pipeline, which would help achieve gender equality at senior levels over time."

The Lancaster study highlighted issues and benefits raised by a case study at a UK university, with two women in a job share able to play to one another's strengths and collectively shoulder responsibility, while needing to have trust and faith in each other.

The researchers found that two parties in a job share could learn from each other and better use their own skills, while the skills of the other were used in different areas. As well as increasing productivity, it also allowed them to identify their own strengths and develop their leadership identity, which enabled future progress towards more senior positions.

"Increased confidence can help to counter the stereotype of a lack of confidence in pursuing a climb up the career ladder," said co-author Sarah Stables, of Stables and Co Innovation Ltd. "Job sharing creates a mentor-type relationship where both can boost the confidence of the other and promote the strengths of the other to stakeholders. As such, it also addresses the self-promotion deficiency to better place them in line for higher-level posts.

"If universities adopted job sharing at all levels, it is highly plausible their ability to both retain existing talented women and to recruit more women would be increased at a stroke."

She added: "Of benefit to organisations is that research shows that job sharing increases productivity, retains highly skilled employees, reduces employee time off due to ill health and increases employee engagement."

While the study focused on higher education, the authors feel their findings can apply across sectors, highlighting for example a lack of women in high-ranking positions within FTSE 250 listed companies.

"Job sharing provides an opportunity to increase women's representation not just in higher education leadership, but in all sectors," added Professor Steve Kempster, of Lancaster University Management School's Department of Entrepreneurship and Strategy. "There are concerns over the pipeline of female leaders in FTSE 250 companies, with an increase seen in the number of male-only boards, so the possibility of job sharing senior leadership roles should be considered."

Fresh evidence has revealed that major tobacco companies in the UK have made attempts to continue to market their products despite the introduction of plain packaging for cigarettes nearly three years ago.

The plain packaging policy was designed to rid tobacco companies of their last remaining method for tobacco advertising. No branded packets could be printed from May 20 2016 and all cigarettes and roll-your-own tobacco had to be in plain packaging by May 20 2017. This year-long period was known as the sell-through.

Yet the latest findings from the Tobacco Control Research Group at the University of Bath, published today (Tuesday 24 September 2019) in the British Medical Journal BMJ Open find that tobacco companies deployed a variety of tactics to get around technicalities in plain packaging legislation.

Their study, funded by Cancer Research UK, suggests companies:

Made product name changes that smokers would relate to the old branded packs. For example, flavour names previously associated with low tar cigarettes (e.g. 'smooth') were changed to colour names (e.g. blue). These colours often replicated the colour of the branded packs. The researchers suggest this facilitated continued misperceptions about the relative harms of products. Research evidence has conclusively shown that 'low tar', 'smooth', 'mild' or 'light' cigarettes are no less harmful than their full-strength counterparts despite what smokers might think.

Used a lengthy 'sell-through' period to their advantage by offering retailers financial incentives to keep branded packs on the market for as long as possible and by using the time to communicate all forthcoming changes to product names.

Introduced features to cheaper brands that are usually confined to more expensive brands due to concerns about smokers down-trading to cheaper brands. For example, several flavour capsule variants such as menthol crush balls were introduced in lower price brackets (these will be banned from 2020). Worryingly, flavour capsule cigarettes have been found to appeal more to non-smokers and non-daily smokers than daily smokers. The availability of such products at more affordable prices may entice those who would not otherwise smoke to do so.

Offered additional sticks in packs to avoid being 'constrained' by a minimum pack size of 20 and trying to tempt smokers to their cheaper brands.

Additionally, cigarette filters, roll-your-own tobacco accessories, cellophane and paper multipack outers, cigars and pipe tobacco were exempt from the legislation and therefore, tobacco companies have increasingly focused their attention on innovating and marketing these products to retailers. The marketing of filter innovations such as 'improved filter, 'firm filter' appears to have the same aim as replacing flavour names with colours, hinting at a potentially reduced risk experience.

Philip Morris International introduced changes to its Marlboro brand, adding bevelled edges, and a new closing mechanism to the packet that endured after the legislation was fully implemented. The researchers suggest this was to make their product appear more premium and recognisable compared to other brands.

The study reviewed data from several sources - retail, trade and industry reports, articles and adverts; routine tobacco pack purchases and commercial tobacco sales data - to explore what changes tobacco companies made to their brand portfolios, product names, pack branding and pack sizes in light of the new legislation.*

Lead author, Dr Karen Evans-Reeves from the University of Bath's Department for Health, explains: "Although compliance with removing branded packs was generally good, the study revealed that tobacco companies engaged in activities that undermined and continues to undermine the legislation.

"Major tobacco companies will always try to find a way to market their products. Based on the number of innovations we found in this study, we would encourage all governments considering implementing plain packaging legislation to consider how tobacco companies have adapted to the legislation in other countries and where possible, close any remaining loopholes."

Kruti Shrotri, Cancer Research UK's tobacco control manager, said: "As expected, the tobacco industry continues to use every tactic they can to promote their deadly products and push up their profits. And at the same time, funding for services to help people quit smoking continue to be slashed. It's time that a levy is introduced to make the tobacco industry pay for the damage they cause to public health."

Emissions of volatile organic pollutants in West Africa are 100 to 150 times higher than current estimates for the region, according to a study by researchers from the CNRS and Université Clermont-Auvergne[1], in collaboration with the Institut Mines Télécom Lille-Douai and Université Felix Houphouët-Boigny (Abidjan, Côte d'Ivoire). The results[2], obtained from field measurements carried out as part of the European DACCIWA[3] programme, highlight the urgent need to set up more realistic and appropriate regional emission inventories in order to better predict their impacts on health, air quality and climate. The study, which took place in Côte d'Ivoire and focused on emissions from road traffic, waste combustion and domestic fires, shows that they far exceed those of all the European countries combined. The paper will be published on 24 September 2019 in Atmospheric Chemistry and Physics.

Conventional wisdom indicates that market discipline and transparency ensures that financial data of public firms are more reliable for potential investors than financial reports from private companies. Contrary to this widely-held belief, new research from the NYU Stern School of Business, University of Bolzano and Bocconi University finds that when comparing European public firms against private firms with similar organizational structures, private firms provide a higher "earnings quality" or EQ, which is a measure of the reliability of financial statements.

Using data over a nine-year period (2005-14), NYU Stern Professor Paul Zarowin, Bolzano Professor and NYU Stern Visiting Professor Massimiliano Bonacchi and Bocconi Professor Antonio Marra examined the EQ of nearly 400,000 European companies across 11 countries.

To effectively compare the EQ of public vs. private firms, the authors first organized the private firms into two categories: (1) standalone entities and (2) business groups. Because all public firms are structured as business groups, the authors compared the financial statements of public companies against those of private business groups, to control for non-market forces (Tax incentive and Stakeholder pressure for earnings quality) that differently affect private groups and standalone firms.

The co-authors conclude that:

When comparing public firms vs. all private firms (both standalone and business groups), public firms have a higher EQ. However, when comparing public firms vs. private business groups only, private firms have a higher EQ.

A notable exception to the rule is the United Kingdom, the most-developed market in Europe, where public companies prove to have more reliable earnings than private ones.

"In less-sophisticated capital markets, incentives to produce high-quality financial statements are not strong enough," explained Professor Zarowin. "Our research shows that public companies often over-report earnings to improve their short-term performance. Because of this trend, investors should be leery of public financial data in many European markets."

"US investors should look with more interest to private European companies," added Professor Bonacchi. "If policymakers want to reverse public firms' relatively low earnings quality, they should give more incentives (and more enforcement) to listed firms to report high-quality earnings, especially in less-developed markets."

"Unfortunately, the lack of available data in the private firms does not allow us to test the US setting," explained Professor Marra. "The United States has high-quality capital markets, but opportunistic reporting is prevalent there, so it is not clear whether similar results would be found."

An algorithm developed by faculty at The University of Texas Health Science Center at Houston (UTHealth) can help physicians outside of major stroke treatment centers assess whether a patient suffering from ischemic stroke would benefit from an endovascular procedure to remove a clot blocking an artery.

Results of their clinical study using the algorithm were published online today in the journal Stroke.

Endovascular thrombectomy is a procedure that involves threading a catheter through the femoral artery in the leg all the way to the brain, where the clot can be removed mechanically. Since 2015, studies have shown it can improve outcomes for stroke patients, but only if the amount of brain tissue that has been injured is minimal at the time of treatment.

Unfortunately, advanced neuroimaging to detect within hours whether a patient is a candidate for the treatment is limited to emergent magnetic resonance imaging or computed tomography (CT) perfusion. That kind of technology and expertise are not available at most community hospitals and primary stroke centers.

"With endovascular thrombectomy, we now have a treatment for ischemic stroke that is really revolutionary. It allows us to take stroke patients from severe disability and return them to an almost normal life," said Sunil A. Sheth, MD, corresponding author and assistant professor of neurology with McGovern Medical School at UTHealth. "Unfortunately, the advanced imaging techniques used currently to identify which patients benefit from this procedure are not widely available outside of large referral hospitals. As a result, most stroke patients don't have access to guideline-based screening for these treatments."

In response, Sheth and Luca Giancardo, PhD, senior author and assistant professor at UTHealth School of Biomedical Informatics, developed a machine-learning tool that could be used with a widely available imaging technique, CT angiogram. The tool can analyze images by automatically "learning" subtle image patterns that can be used as a proxy for other more advanced, but not readily available, imaging modalities such as CT perfusion. The machine learning architecture, called DeepSymNet, was developed at UTHealth.

To test the tool, the research team identified patients in their stroke registry who had suffered a stroke or had conditions that mimicked stroke.

Of the 224 who had stroke, 179 had cerebral blood vessels that were blocked. The DeepSymNet algorithm learned to identify these blockages from the CT angiogram images, and trained the software to use those same images to define the area of brain that had died, using concurrent acquired CT perfusion scans as the "gold standard."

"The advantage is you don't have to be at an academic health center or a tertiary care hospital to determine whether this treatment would benefit the patient. And best of all, CT angiogram is already widely used for patients with stroke," Sheth said.

Washington State University scientists have developed a way to triple the shelf life of ready-to-eat macaroni and cheese, a development that could have benefits for everything from space travel to military use.

If human beings go to Mars, they need food. Food that won't spoil during the long travel between planets, and while they're on the surface.

Currently, plastic packaging can keep food safe at room temperature for up to twelve months. The WSU researchers demonstrated in a recent paper in the journal Food and Bioprocess Technology they could keep ready-to-eat macaroni and cheese safe and edible with selected nutrients for up to three years.

"We need a better barrier to keep oxygen away from the food and provide longer shelf-life similar to aluminum foil and plastic laminate pouches," said Shyam Sablani, who is leading the team working to create a better protective film. "We've always been thinking of developing a product that can go to Mars, but with technology that can also benefit consumers here on Earth."

In addition to having space travel in mind, the researchers are working closely with the U.S. Army, who want to improve their "Meals Ready to Eat" (MREs) to stay tasty and healthy for three years.

In taste panels conducted by the Army, the mac and cheese, recently tested after three years of storage, was deemed just as good as the previous version that was stored for nine months.

How it works

The food itself is sterilized using a process called the microwave-assisted thermal sterilization (MATS) system, developed by WSU's Juming Tang. The food must be sterilized in plastic, since metal, like tin cans, can't be microwaved and glass is fragile and not a preferred choice of packaging for MREs. Glass is also too heavy for military or space uses.

Adding a metal oxide coating to a layer of the plastic film significantly increases the amount of time it takes for oxygen and other gases to break through.

The metal oxide coating technology has been around for almost 10 years, but it develops cracks when subjected to sterilization processes. That eventually compromises the food shelf-life, said Sablani, a professor in WSU's Department of Biological Systems Engineering. WSU researchers have been working with packaging companies to develop new films that keep oxygen and vapor out longer.

The packaging films are made up of multiple layers of different plastics. These few-micron thin layers have different purposes, like being a good barrier, good for sealing, good mechanical strength, or good for printing, Sablani said.

"We are excited that an over-layer of organic coating on metal oxide helped protect against microscopic cracks," he said. "Multiple layers of metal oxide coating have also increased the barrier performance. Our research guided development of newer high barrier packaging."

Real-world testing

To ensure the process works fully, the Army plans to do testing under field conditions. So these new MREs will be stored longer, then sent to deployed soldiers to eat in the field.

"If they like the taste of the packaged food there, then that's the ultimate test of new films," Sablani said.

The team doesn't wait the three years to test the results of each new film. Keeping the packaged food in a 100-degree Fahrenheit incubator rapidly speeds up the food quality changes at a consistent rate. Six months in the incubator is equivalent to three years at room temperature, while nine months is the equivalent to nearly five years, Sablani said.

Space testing

For space travel, it's not really possible to field-test for a trip to Mars. But Sablani plans to reach out to NASA to talk about how to test the WSU films to make sure that packaged food stays edible on a space mission where failure isn't an option.

"NASA knows about our work, but we're just now getting to the point where we can talk to them with a proven product," Sablani said. "We hope to work out a way to test these products on the International Space Station in the future to show that the food is safe after long-term storage."

NASA will require storage of up to five years for food, so that's what the team is working on now. They are currently aging other recipes that will be taste tested once they reach the five year mark.

Several types of mission plans have been proposed for a trip to Mars. The five-year food storage includes some built-in safety requirements, Sablani said.

It may involve an approximately nine month travel time from Earth to Mars, about five hundred days on or orbiting Mars, and a travel time of about nine months to return to Earth. The extra storage time is necessary in case the mission is delayed and explorers must stay longer.

ANN ARBOR--As neighborhood and city planners design ways to reuse vacant land in cities like Detroit, a researcher at the University of Michigan is urging them to look at the footpaths of people who already live there--literally.

In what's believed to be the first comprehensive study of unofficial footpaths in a large urban area, U-M's Joshua Newell and colleague Alec Foster of Illinois State University mapped 5,680 unofficial footpaths in the city of Detroit--that's 157 linear miles of trails--visible from space.

They discovered a 70% decline in the total length of footpaths on Detroit's far east side between 2010 and 2016, with almost half of the lost footpaths on publicly owned land.

The reasons for the changes varied by neighborhood. Sometimes, new land ownership meant fences and development on land that was once vacant. Other times, the land where the footpath once stood became unkempt and so overgrown that it was unusable even for a footpath.

In all, 758 Detroit footpaths were lost over the six years, and 99 new ones were created. The study's findings are featured in the September issue of the journal Landscape and Urban Planning.

"When traveling in Detroit, doing work on urban gardens, I was struck by all the footpaths," said Newell, associate professor at U-M's School for Environment and Sustainability and in the Program in the Environment. "There is so much vacant land, we are not going to be able to develop or simply enclose all of it ... so why not think about reaffirming and formalizing how people are already using these spaces?"

Detroit boasted a 1.9 million population at its height but as of 2016 numbered 670,000 residents. Such a massive exodus of people and employers has led to blocks and blocks of city land with few houses or even buildings. About 23 square miles of vacant land exists in Detroit, which is roughly equivalent to the entire island of Manhattan.

These vacant parcels are spread throughout the city's roughly 140 square miles, and the footpaths are residents' way of dealing with this reality, creating shortcuts to school, bus lines and other places they need to go.

This idea of people creating footpaths that become official roads is not new. Many of the paved roads in Michigan can trace their origins as pathways made by Native Americans before European settlers arrived.

Yet with many of Detroit's footpaths in neighborhoods of greatest poverty, highest numbers of minorities and largest percentage of vacant land, the issue is a matter of social justice, Newell says.

And when the paths disappear, as happened in Detroit's lower east side because of changes in land ownership and path abandonment, there is lost opportunity to use the land in an organic way, including the voice and wishes of the people who already live there.

"These paths are the neighborhoods expressing their desire for how the land should be used by walking across it," Newell said.

CLEVELAND, Ohio (September 24, 2019)--Childhood abuse has been shown to lead to an array of health problems later in life. A new study now shows that such abuse may be linked with physiologically detected hot flashes. Study results will be presented during The North American Menopause Society (NAMS) Annual Meeting in Chicago, September 25-28, 2019.

Hot flashes are the focus of many research studies, especially since newer data has indicated that they may last longer than previously thought-some as long as 10+ years. Previous research has shown a relationship between childhood abuse and hot flashes. However, this prior work has only used self-reported measures of hot flashes. Physiologic measurements of hot flashes are important given difficulties reporting hot flashes, particularly during sleep. Further, the studies have not looked at changes in hot flashes over time, which is important given how long hot flashes can last.

The researchers leveraged a unique study that employed longitudinal physiologic measurements of hot flashes at two time points over five years to show that childhood abuse was associated with more sleep hot flashes, both at a single time point, as well as increases in hot flashes over five years, after adjusting for age, race/ethnicity, education, and BMI.

"Our investigation found that childhood sexual and physical abuse were associated with more frequent hot flashes during sleep when measured at a single time point. We also learned that women with a history of emotional abuse showed an increase in hot flashes five years later, whereas their non-abused counterparts showed a decrease in hot flashes five years later," says Mary Carson, lead author of the study from the Department of Psychology at the University of Pittsburgh.

"Hot flashes can significantly affect a woman's quality of life, so studies like these are important in helping healthcare providers understand all of the variables associated with them," says Dr. Stephanie Faubion, NAMS medical director.

Mary Carson and Dr. Faubion are available for interviews before the presentation at the Annual Meeting.

CLEVELAND, Ohio (September 24, 2019)--Certain species of bacteria are actually necessary to maintain vaginal health. The menopause transition, however, often upsets the natural balance of bacteria by decreasing the proportion of healthy bacteria and increasing vaginal pH. This can result in urogenital infections and other vaginal health problems. The importance of vaginal bacterial colonization patterns during menopause will be discussed at The North American Menopause Society (NAMS) Annual Meeting in Chicago, September 25-28, 2019.

The community of microbes colonizing the vagina has a profound impact on reproductive and sexual health. The bacterial genus Lactobacillus dominates in healthy vaginas, protecting women from urogenital infections by maintaining a low pH level of less than 4.5. They are also associated with a lower risk for HIV acquisition, bacterial sexually transmitted infections, and persistent HPV infection in premenopausal women.

After menopause, however, the proportion of lactobacilli typically decrease in the vagina, making women more vulnerable to genital infections, urinary tract infections, and cervical dysplasia. To date, few studies have focused on this association in postmenopausal women, so it has yet to be proven whether the decolonization of healthy bacteria also causes common postmenopausal vaginal discomfort.

Currently, the most reliable strategy for promoting vaginal Lactobacillus colonization after menopause is treatment with estrogen. However, additional therapies are in development, including oral and vaginal probiotics. These strategies, along with a discussion regarding changes in vaginal microbes during menopause, will be addressed at the upcoming NAMS Annual Meeting by Dr. Caroline Mitchell from Harvard Medical School and Massachusetts General Hospital.

"It is important that women and their healthcare providers understand the important role played by bacteria in the vagina and the limitations of current strategies for modulating the vaginal microbiota after menopause, due to a lack of robust data," says Dr. Mitchell. "Women deserve correct information about what we do and don't know."

"With so many postmenopausal women affected by vulvovaginal atrophy, vaginal dryness, and a related decrease in their overall quality of life, this topic is expected to have widespread appeal and the presentation will likely educate healthcare providers on the latest treatment options," says Dr. Stephanie Faubion, NAMS medical director.