Earth

Pharmacies leave customers hanging when it comes to disposing of antibiotics and opioids

Proper disposal of leftover medication, particularly antibiotics and opioids, can help reduce antibiotic resistance, prevent children from being poisoned and stop the misuse of addiction-forming drugs.

But a telephone survey conducted by researchers at UC San Francisco found that fewer than half of California pharmacies provided disposal instructions meeting U.S. Food and Drug Administration guidelines, and just 10 percent followed the FDA's preferred recommendation to take back unused medications from their customers.

Over a two-month period in early 2018 researchers posing as parents of children who had recently had surgery spoke to employees at nearly 900 pharmacies in California and asked them what to do with two leftover medications: the antibiotic Bactrim (sulfamethoxazole-trimethoprim), and liquid Hycet (hydrocodone-acetaminophen), a pain reliever containing an opioid compound.

Neither medication should be left in the medicine cabinet, since the antibiotics could be taken improperly for subsequent infections they cannot cure, contributing to antibiotic resistance, and opioids can fall into the wrong hands.

In the absence of a takeback program, the FDA says antibiotics should be mixed with an unpalatable substance, such as coffee grounds or kitty litter, and disposed of in a sealed container in the trash to keep them from getting into the water supply or inadvertently ingested. The FDA recommends that opioids be flushed down a toilet, since people may otherwise find and accidentally ingest or intentionally abuse them, even when they've been mixed with an unpalatable substance and thrown into the trash.

Overall, just 47 percent of pharmacies gave the correct instructions on how to dispose of antibiotics, and only 34 percent gave correct instructions for opioids.

"This clearly points to the need for better dissemination of information on proper medication disposal," said Hillary Copp, an associate professor of urology at UCSF and the senior author of the study, published Monday, Dec. 30, 2019, in Annals of Internal Medicine. "The FDA has specific instructions on how to dispose of these medications, and the American Pharmacists Association has adopted this as their standard. Yet it's not being given to the consumer correctly the majority of the time."

Copp stressed that improving disposal practices will require both better efforts to educate patients, and those who advise them, as well as expanded disposal programs to ensure that patients have a place to take unused medication. At UCSF, Copp said, physicians are working to uniformly incorporate disposal instructions into the information that patients receive when they are discharged.

"A pharmacy is a place where medications are dispensed so it is natural for people to look to this same location for advice on how to dispose of unused medications," Copp said. However, she added, "pharmacies should not be solely responsible for providing proper disposal information. Managing leftover medications is a complex problem that should be addressed from multiple angles."

Credit: 
University of California - San Francisco

A fragile balance

image: An international team of scientists led by the University of Oldenburg, Germany, used measurements on fossil skeletons of the cold-water coral Desmophyllum dianthus to reveal that significant changes in deep-water circulation occurred in the Drake Passage, a narrow strait between Antarctica and South America, around six to seven thousand years ago. The scientists see indications that these changes also influenced CO2 levels in the atmosphere - and suggest that future climate change could lead to increased release of CO2 from the deep waters of the Southern Ocean into the atmosphere.

Image: 
Andrew Margolin

The sea encircling Antarctica acts as a huge mixer for water from all the ocean basins - and this circulating pattern influences the exchange of carbon dioxide (CO2) between the ocean and the atmosphere. A study by an international team of researchers, led by Dr. Torben Struve from the University of Oldenburg's Institute for Chemistry and Biology of the Marine Environment (ICBM), has now established that this complex equilibrium of water masses reacts highly sensitively to wind conditions over the Southern Ocean.

The study, which is published in the scientific journal Proceedings of the National Academy of Sciences, used measurements on fossil coral skeletons to reveal that significant changes in deep-water circulation occurred in the Drake Passage, a narrow strait between Antarctica and South America, around six to seven thousand years ago. The scientists see indications that these changes also influenced CO2 levels in the atmosphere - and suggest that future climate change could lead to increased release of CO2 from the deep waters of the Southern Ocean into the atmosphere.

"The Southern Ocean connects all the world's oceans. It's one of the few places on Earth where water from great depths comes to the surface and at the same time surface water sinks to the depths," explained lead author Struve. The marine region around Antarctica is therefore critical for the global conveyor belt of ocean currents, which distributes heat, nutrients, salt and CO2 over great distances.

However, until now, it had not been clear whether the current flowing in the Southern Ocean had changed significantly since the last ice age ended about 12,000 years ago. Previous studies by climate researchers had shown that there have been several shifts in the strong westerly winds blowing around Antarctica during the current interglacial period.

These winds drive the Antarctic Circumpolar Current (ACC), a cold ocean current that extends from the surface to the ocean floor and which connects the Atlantic, Indian and Pacific Oceans. Importantly, the winds also stimulate the upwelling of deep ocean waters towards the ocean surface. The study set out to determine how the currents in the Southern Ocean reacted to these changes in the atmosphere.

To answer this question, Struve and his colleagues from Imperial College London, University College London and the University of Edinburgh, analysed fossil cold-water corals from the Drake Passage, some of which were several thousand years old. The corals were collected from different water depths at three locations in the Drake Passage during two expeditions with the US research vessel Nathaniel B. Palmer.

"This area is notorious for its poor weather conditions - simply collecting the samples was a challenge," Struve explained.

The cold-water corals store certain trace elements, such as neodymium, in their calcareous skeletons, and therefore record a chemical fingerprint of the water they grew in.

Analyses of the neodymium fingerprints in the coral samples showed that there was an abrupt change in the chemical composition of the water about 7,000 years ago, which lasted for about 1,000 years. On the basis of several findings, the team concluded that increased amounts of CO2-rich deep water from the Pacific Ocean penetrated the Drake Passage at that time, presumably driven by a northwards shift of the Southern Hemisphere westerly winds.

"This was a surprising result for us. We hadn't expected the Southern Ocean to react so sensitively during an interglacial period," said Struve. "This study highlights the invaluable contribution of cold water coral fossils to understanding past climate change. They provide unique records of the chemical composition of seawater - often in regions of the ocean where other types of archives are scarce," co-author Dr. Kirsty Crocket of the University of Edinburgh underlined.

The study also sheds light on a series of other climate changes that occurred around the same time. In particular, atmospheric CO2 levels, which had dropped slightly in the preceding 2,000 years, began to rise once more. Struve and his colleagues suspect that a key source for this phenomenon was an increase in the amount of CO2-rich Pacific deep water in the Southern Ocean.

"This is important because when deep waters upwell to the surface of the Southern Ocean, some of the stored CO2 is able to escape to the atmosphere", explained co-author Dr. David Wilson. And then, as the winds shifted southwards once more, this upwelling increased and larger amounts of CO2 were released into the atmosphere.

It is not yet clear how rising global temperatures will affect the ocean currents encircling Antarctica. However, current climate scenarios indicate that the Southern Hemisphere westerly winds will move further south towards Antarctica. This scenario could lead to stronger mixing of water masses in the Southern Ocean and more upwelling - which the team of researchers suspects could in turn result in larger amounts of CO2 being released from the deep ocean.

Credit: 
University of Oldenburg

NASA sees Mauritius covered by Tropical Storm Calvinia

image: On Dec. 30, 2019, the MODIS instrument that flies aboard NASA's Terra satellite provided a visible image of Tropical Storm Calvinia covering the island of Mauritius in the Southern Indian Ocean.

Image: 
NASA Worldview

Tropical Cyclone Calvinia formed on Dec. 29 and by the next day, its clouds from a band of thunderstorms on its western side had blanketed the island of Mauritius in the Southern Indian Ocean.

Calvinia's center was just east of the island on Dec. 30. The storm has triggered a tropical cyclone warning class III in Mauritius.

On Dec. 30, 2019, the Moderate Imaging Spectroradiometer or MODIS instrument that flies aboard NASA's Terra satellite provided a visible image of Calvinia that showed the storm had a rounded shape. A rounded shape of a tropical cyclone indicates an organized storm. The MODIS image revealed bands of thunderstorms from the western side spiraled into the low-level center of circulation. That thick band of thunderstorms blanketed Mauritius bringing gusty winds and heavy rains.

On Dec. 30 at 0300 UTC (Dec. 29 at 10 p.m. EST) the Joint Typhoon Warning Center noted that Tropical Cyclone Calvinia was located near 20.6 degrees south latitude and 58.8 degrees east longitude. That is about 90 nautical miles east-southeast of Mauritius. Maximum sustained winds 35 knots (40 mph). This storm if moving to the southwest.

Calvinia is forecast to strengthen to 55 knots and curve to the southeast and away from Mauritius and St. Denis.

NASA's Terra satellite is one in a fleet of NASA satellites that provide data for hurricane research.

Tropical cyclones are the most powerful weather event on Earth. NASA's expertise in space and scientific exploration contributes to essential services provided to the American people by other federal agencies, such as hurricane weather forecasting.

Credit: 
NASA/Goddard Space Flight Center

Replacing one gas with another helps efficiently extract methane from permafrost

Scientists from Skoltech and Heriot-Watt University proposed extracting methane by injecting flue gas into permafrost hydrate reservoirs. Since the flue gas contains carbon dioxide, the new technology will also contributes to reduction of this green house gas in the Arctic atmosphere. The results of their study were published in the journal Scientific Reports.

The Russian Arctic is actively developing due to exploitation of recently discovered oil and gas fields. However, operations in the Arctic region face numerous geological challenges. One of the most serious of them is formation of gas hydrates in frozen rock mass. Gas hydrates are ice-like crystalline structures formed by water and gas molecules. Their accumulations strongly hinders oil and gas field development and triggers spontaneous methane emissions into the atmosphere on the Arctic coast and shelf.

The scientists from the Skoltech Center for Hydrocarbon Recovery (CHR) and from Heriot-Watt University (Edinburgh, Scotland) developed a unique method for extracting methane from permafrost gas-hydrates by injecting flue gases, generated by fuel combustion. The main sources of flue gas are waste gases from coal-burning power plants and metallurgical plants and other industrial facilities.

The research team has found optimal injection conditions and identified the effect of flue gases on the efficiency of methane recovery. It is important to emphasize that flue gas contains considerable amount of green-house carbon dioxide, that will also be buried subsurface. The carbon dioxide forms hydrate replacing the original methane hydrate. The new technology is essential for development of the hydrocarbon fields in the highly sensitive Arctic environment.

"Our approach not only helps extract methane and prevent its free release into the atmosphere but also reduce carbon dioxide emissions. I would say our method offers a double dividend in terms of environmental safety," says Leading Research Scientist at CHR, Evgeny Chuvilin.

Credit: 
Skolkovo Institute of Science and Technology (Skoltech)

Individualized physical therapy reduces incontinence, pain in men after prostate surgery

image: Dr. Kelly Scott

Image: 
UTSW

DALLAS - Dec. 30, 2019 - For decades, therapy to strengthen pelvic muscles has been the standard treatment for men dealing with urinary incontinence after prostate surgery. But a new study from UT Southwestern's Departments of Urology and Physical Medicine and Rehabilitation suggests that may not be the best approach.

The study examined records from post-prostatectomy patients with stress urinary incontinence - meaning loss of bladder control while sneezing, bending over, etc. - who received physical therapy between 2009 and 2014. Researchers found most had some muscle "overactivity" - muscle tightness or spasms - rather than just muscle weakness, says Kelly M. Scott, M.D., an associate professor in the Department of Physical Medicine and Rehabilitation at UT Southwestern and first author of the study.

Using exercise in an attempt to strengthen a tight or spasming muscle can be counterproductive, making the muscle tighter instead of stronger, says Michelle H. Bradley, a physical therapist with the Comprehensive Pelvic Rehabilitation Program in the Physical Medicine Department and a co-author of the study.

Of the 136 therapy patients whose records were reviewed for this study, 25 had only weak, or "underactive," pelvic floor muscles, 13 had overactive or tight muscles, and 98 had evidence of both, according to the study, now online and publishing soon in an upcoming issue of International Urology and Nephrology.

"That was actually a very surprising finding," Scott says of the large number of patients with both tight and weak pelvic floor muscles.

Tense muscles can be a protective mechanism after injury from surgery, she explains. Part or all of the prostate surrounding the urethra is removed in a prostatectomy, usually because of cancer. "But the study's findings are counter to the prevailing idea, which is that these men must have very weak muscles."

Almost every patient has incontinence immediately after a prostatectomy, Scott says, but that percentage drops to about 5 to 20 percent within two years after surgery. Those who haven't seen improvement within two to six months should seek physical therapy, she says.

Standard treatment has focused on strengthening exercises, sometimes using so-called Kegel exercises that involve repetitions of contracting, then releasing, muscles. Recently, doctors and therapists have begun evaluating patients to determine the right therapy rather than assuming the problem was muscle weakness, Scott says. However, there have been few, if any, studies looking at the effectiveness of this targeted approach, she says.

"This is perhaps the first study to look at the type of muscle dysfunction present in men after they've had this surgery. Are the muscles actually weak and need to be strengthened, or are they actually tight and just need to be relaxed and lengthened?" she asks.

After a therapist's evaluation, the men - all patients of Claus Roehrborn, M.D., senior author of the study and a surgeon, professor, and chair of the Department of Urology - received therapy to either relax or strengthen their pelvic muscles.

In 87 percent, incontinence improved, with 58 percent achieving what is considered the optimal improvement of needing two or fewer protective pads per day, according to the study.

Pain was also a problem for 27 percent of the patients, the study showed. The number with pain dropped to 14 percent by the end of therapy, which averaged slightly more than four sessions. In those who still had some pain, the reported level was reduced. "This is the first study to show a decrease in post-prostatectomy pain after therapy," Scott says.

These findings should encourage others to launch studies to test individualized physical therapy, Roehrborn says.

"If patients can get stronger by relaxing their muscles, then there's more work to be done to figure out the best way to treat these patients," Scott says.

Credit: 
UT Southwestern Medical Center

North Atlantic Current may cease temporarily in the next century

image: This image shows the Atlantic Ocean Circulation, which transports relatively warm water from the Gulf of Mexico to north-western Europe.

Image: 
Sven Baars, University of Groningen

The North Atlantic Current transports warm water from the Gulf of Mexico towards Europe, providing much of north-western Europe with a relatively mild climate. However, scientists suspect that meltwater from Greenland and excessive rainfall could interfere with this ocean current. Simulations by scientists from the University of Groningen and Utrecht University showed that it is unlikely that the current will come to a complete stop, due to small and rapid changes in precipitation over the North Atlantic. However, there is a 15 percent likelihood that there will be a temporary change in the current in the next 100 years. The results were published on 30 December in the journal Scientific Reports.

'The oceans store an immense amount of energy and the ocean currents have a strong effect on the Earth's climate,' says University of Groningen Associate Professor in Numerical Mathematics, Fred Wubs. Together with his colleague Henk Dijkstra from Utrecht University, he has studied ocean currents for some 20 years.

Box model

Ocean scientists have found that the Atlantic Ocean currents are sensitive to the amount of fresh water at the surface. Since the run-off of meltwater from Greenland has increased due to climate change, as has rainfall over the ocean, it has been suggested that this may slow down or even reverse the North Atlantic Current, blocking the transport of heat to Europe.

Simulations of the effects of freshwater on the currents have already been performed for some decades. 'Both high-resolution models, based on the equations describing fluid flows, and highly simplified box models have been used,' explains Wubs. 'Our colleagues in Utrecht created a box model that describes present-day large-scale processes in the ocean rather well.'

Total collapse

The idea was to use this box model to estimate the likelihood of small fluctuations in freshwater input causing a temporary slowing down or a total collapse of the North Atlantic Current. The current shows non-linear behaviour, which means that small changes can have large effects. The evolution of the physics described by the box model can only be obtained using simulations. 'As the transitions we were looking for are expected to be rare events, you need a huge number of simulations to estimate the chance of them happening,' says Wubs. However, the Dutch scientists found that a French scientist had devised a method to select the most promising simulations, reducing the number of full simulations required.

Sven Baars, a PhD student of Wubs, implemented this method efficiently and linked it to the Utrecht box model. Daniele Castellana, a PhD student of Dijkstra, performed the simulations. 'These simulations showed that the chances of a total collapse of the North Atlantic Current within the next thousand years are negligible,' says Wubs.

Interruption

A temporary interruption in the delivery of relatively warm water to north-western Europe is more likely: 'In our simulations, the chances of this happening in the next 100 years are 15 percent.' Such temporary transitions may cause cold spells in the North Atlantic, although this needs to be verified in further studies. Therefore, the current study is just a first step in determining the risk. The model does not take into account considerable changes in freshwater in the North Atlantic, which can be caused by the melting of the ice sheets. Wubs: 'Confirming our results through simulation with a high-resolution climate model will be the next challenge.'

Credit: 
University of Groningen

Better anchor roots help crops grow in poor soils

image: A newly identified metabolite that stimulates anchor root growth in Arabidopsis plants may have potential applications in promoting plant growth in nutrient-deficient soils. The two plants treated with anchorene (right) show anchor root formation while untreated plants do not show anchor root formation.

Image: 
© 2019 KAUST

A metabolite in plants that regulates the growth of anchor roots--vital for sustaining water and nutrient uptake in plants--has been identified and may have useful applications in agriculture.

Pigment compounds called carotenoids are found in all plants and play a key role in successful photosynthesis and the generation of plant hormones and metabolites. These products are formed when enzyme activity causes carotenoid molecules to split--a process known as cleavage. While many carotenoid products are known to play key biological roles, less is known about one group of cleavage molecules called di-apocarotenoids.

"Di-apocarotenoids have rarely been characterized due to their instability and low abundance," says KAUST research scientist Kunpeng Jia, who worked on the project under the supervision of KAUST's Salim Al-Babili. "Indeed, we are only beginning to understand what their biological significance might be and what functions they have."

The KAUST researchers, in collaboration with scientists in the United States and Germany, conducted an extensive study on the presence and biological activities of di-apocarotenoids in Arabidopsis plants using developmental studies and state-of-the-art analytical chemistry techniques. Working with such inherently unstable compounds that have low molecular weights within plant tissues was a real challenge for Jianing Mi, from Al-Babili's team, who honed lab techniques to extract and analyze the molecules without damaging them.

"We identified the di-apocarotenoid anchorene as a metabolite that sends a specific signal to trigger the formation of Arabidopsis anchor roots," says Jia. "Because anchorene is a carotenoid product, correct carotenoid biosynthesis is also required for healthy root formation. We confirmed this using chemical inhibitors and Arabidopsis mutants."

Further experiments showed that anchorene modulates the distribution of the plant hormone auxin in the anchor root formation site, which stimulates growth. Jia and coworkers found that increasing anchorene levels in carotenoid-deficient plants rescued anchor root growth, while promoting growth in normal seedlings. When they modified anchorene's structure, it resulted in loss of activity.

"We'd like to explore the biological importance of anchorene further, and we also hope to understand exactly how plants produce this metabolite," says Jia. "We will also examine the biological activity of anchorene in crop plants because our findings may be relevant in boosting yields."

"Anchorene changes the root architecture by promoting anchor root formation, which increases root volume and facilitates water and nutrient absorption," adds Al-Babili. "Therefore, it may be possible to apply anchorene in nutrient-deficient soils to promote root growth."

Credit: 
King Abdullah University of Science & Technology (KAUST)

Short or long sleep associated with Pulmonary Fibrosis

video: Body clock in lung tissue

Image: 
University of Manchester

Scientists have discovered that people who regularly sleep for more than 11 hours or less than 4 hours are 2-3 times more likely to have the incurable disease, pulmonary fibrosis, compared to those that sleep for 7 hours in a day. They attribute this association to the body clock.

The study also reveals that targeting the body clock reduces fibrosis in vitro, revealing a potential target for this incurable disease that kills about 5,000 people, a year in the U.K.,the same number as leukaemia.

The research team members are based at the Universities of Manchester, Oxford, Newcastle, University College London, and Toronto, as well as Manchester University NHS Foundation Trust.

The study is published in Proceedings of the National Academy of Sciences and is funded by the Medical Research Council, and the Wellcome Trust.

Our internal body clocks regulate nearly every cell in the human body, driving 24-hour cycles in many processes such as sleeping, hormone secretion and metabolism.

In the lungs, the clock is mainly located in the main air carrying passages - the airways. However, the team discovered that in people with lung fibrosis, these clock oscillations extend out to the small air spaces, called alveoli.

Studies in mice revealed that by altering the clock mechanism it was possible to disrupt the fibrotic process making the animals more likely to develop pulmonary fibrosis.

The researchers then showed, that pulmonary fibrosis is associated with short and long sleep duration using human data from the UK Biobank.

The link between sleep duration and lung fibrosis is similar in strength to other known risk factors for this disease.

People who report they regularly sleep 4 hours or less in a day doubled their chance of having pulmonary fibrosis while those sleeping 11 hours or longer in a day tripled their chance of having the disease, compared to those sleeping 7 hours per day.

Smaller, but still elevated, risks were also seen in people who like to stay up late at night or those who do shift work.

The researchers explain their findings by the discovery that a core clock protein (REVERBα) which alters the production of a key protein in lung fibrosis (collagen).

This is an exciting finding, they say, because chemical compounds can alter the function of REVERBα.

The authors were able to show that one of these REVERBα compounds can reduce collagen in lung slices from people with this disease.

Dr John Blaikley from The University of Manchester, who led the project said: "Pulmonary fibrosis is a devastating condition which is incurable at present. Therefore, the discovery that the body clock is potentially a key player potentially opens new ways to treat or prevent the condition. More work will need to be done around studying the association between pulmonary fibrosis and sleep duration to establish both causation and reproducibility. If these results are confirmed, then sleeping for the optimal time may reduce the impact of this devastating disease."

Dr Peter Cunningham, joint lead author on the paper, said: "It is fascinating to think that clock activity is increased in fibrotic disease. Previous studies have shown that the clock also plays an important role in infection, cancer and diabetes. The discovery that the clock plays a role in fibrosis suggests that altering these oscillations could become an important therapeutic approach."

Credit: 
University of Manchester

On nitroglycerin, cardiovascular homeostasis and...bam, migraine!

London, UK: A clinical investigation recently published in the journal Cephalalgia, the official journal of the International Headache Society, suggests that migraine patients may exhibit a systemic pathophysiological alteration. The study, entitled "Abnormal cardiovascular response to nitroglycerin in migraine", was conducted by Dr. Willebrordus PJ van Oosterhout, from Leiden University Medical Centre, Department of Neurology, Leiden, The Netherlands.

Nitroglycerin (NTG) is a potent vasodilator and is known to induce migraine attacks in migraine patients. Because of its vasodilating properties, NTG is used in cardiovascular research to test cardiovascular adjustments in face of changes in blood pressure secondary to blood venous pooling. For example, NTG is used to test baroreflex function in individuals with vasovagal syncope, which is more common in migraine patients.

Dr. van Oosterhout and colleagues assessed cardiovascular parameters through photopletismography (blood pressure, heart rate, stroke volume, cardiac output, peripheral resistance) before (-10 min.), during the infusion of NTG intravenously (20 min.), and after the NTG infusion (10 min.) They compared differences between migraine patients who had NTG-triggered attacks and healthy people. The presence of vasovagal syncope was assessed as well.

Ten healthy participants and 16 migraine patients were included in the study. Thirteen out of 16 patients (81.3 %) had migraine attacks following NTG infusion, against none from the control group. No vasovagal syncope was provoked. Migraine patients showed higher heart rate response to NTG infusion. In a subgroup analysis with migraine patients group split into patients with early-onset attacks (those whose attacks occurred 270 min.), stroke volume and cardiac output were reduced in both migraine groups compared to healthy control group, with more pronounced reductions in the early-onset migraine attacks group.

The authors' interpretations of these data are cautious, as the study was underpowered with a small sample. In a speculative tone, Dr van Oosterhout says: "The enhanced response of the systemic circulation to nitroglycerin in migraineurs suggests that the systemic vasculature is more susceptible to its (vasodilatory) effects". And follows: "Sensitivity to nitric oxide (NO) may be enhanced, possibly due to higher perivascular concentrations of NO synthase". Finally, although no participant had vasovagal syncope, the authors do not rule out a common susceptibility of migraine attacks and vasovagal syncope, as some patients in this study had also experienced vasovagal syncope in life.

Credit: 
International Headache Society

Eye changes from spaceflight compared to simulated weightlessness

What The Study Did: Some astronauts who fly long missions to the International Space Station experience eye changes. This study investigated whether the eye changes from the traditional spaceflight analog (an experience on earth meant to mimic spaceflight) of simulated weightlessness from 30 days of bed rest with head tilted down were similar to those experienced by astronauts during spaceflight.

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

Authors: Steven S. Laurie, Ph.D., of KBR in Houston, is the corresponding author.

(doi:10.1001/jamaophthalmol.2019.5261)

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

Credit: 
JAMA Network

Brain tumor organoids may be key to time-sensitive treatments for glioblastomas

PHILADELPHIA --Lab-grown brain organoids developed from a patient's own glioblastoma, the most aggressive and common form of brain cancer, may hold the answers on how to best treat it. A new study in Cell from researchers at Penn Medicine showed how glioblastoma organoids could serve as effective models to rapidly test personalized treatment strategies.

Glioblastoma multiforme (GBM) remains the most difficult of all brain cancers to study and treat, largely because of tumor heterogeneity. Treatment approaches, like surgery, radiation and chemotherapy, along with newer personalized cellular therapies, have proven to slow tumor growth and keep patients disease-free for some periods of time; however, a cure remains elusive.

"While we've made important strides in glioblastoma research, preclinical and clinical challenges persist, keeping us from getting closer to more effective treatments," said senior author Hongjun Song, PhD, Perelman Professor of Neuroscience in the Perelman School of Medicine at the University of Pennsylvania. "One hurdle is the ability to recapitulate the tumor to not only better understand its complex characteristics, but also to determine what therapies post-surgery can fight it in a timelier manner."

Co-senior authors include Guo-li Ming, MD, PhD, Perelman Professor of Neuroscience, and Donald O'Rourke, MD, the John Templeton, Jr., MD Professor in Neurosurgery, and director of the GBM Translational Center of Excellence at Penn's Abramson Cancer Center.

Lab-grown brain organoids -- derived from human pluripotent stem cells or patient tissues and grown to a size no bigger than a pea -- can recapitulate important genetic composition, brain cell type heterogeneity, and architecture, for example. These models are allowing researchers to recreate key features of patients' diseased brains to help paint a clearer picture of their cancer, and allowing them to explore ways to best attack it.

What makes organoids so attractive in GBM is timing and the ability to maintain cell type and genetic heterogeneity. While existing in vitro models have added to researchers' understanding of the biological mechanisms underlying the cancer, they have limitations. Unlike other models, which need more time to exhibit gene expression and other histological features that more closely represent the tumor, brain tumor organoids developed by the research group grow into use much more rapidly. That's important because current treatment regimens are typically initiated one month following surgery, so having a road map sooner is more advantageous.

In the new study, the researchers removed fresh tumor specimens from 52 patients to "grow" corresponding tumor organoids in the lab. The overall success rate for generating glioblastoma organoids (GBOs) was 91.4 percent, with 66.7 percent of tumors expressing the IDH1 mutation, and 75 percent for recurrent tumors, within two weeks. These tumor glioblastoma organoids can also be biobanked and recovered later for analyses.

Genetic, histological, molecular analyses were also performed in 12 patients to establish that these new GBOs had largely retained features from the primary tumor in the patient.

Eight GBO samples were then successfully transplanted into adult mouse brains, which displayed rapid and aggressive infiltration of cancer cells and maintained key mutation expression up to three months later. Importantly, a major hallmark of GBM -- the infiltration of tumor cells into the surrounding brain tissue -- was observed in the mouse models.

To mimic post-surgery treatments, the researchers subjected GBOs to standard-of-care and targeted therapies, including drugs from clinical trials and chimeric antigen receptor T (CAR-T) cell immunotherapy. For each treatment, researchers showed that the organoid responses are different and effectiveness is correlated to their genetic mutations in patient tumors. This model opens the possibility for future clinical trials for personized treatment based on individual patient tumor responses to various different drugs.

Notably, the researchers observed a benefit in the organoids treated with CAR T therapies, which have been used in ongoing clinical trials to target the EGFRvIII mutation, a driver of the disease. In six GBOs, the researchers showed specific effect to patient GBOs with the EGFRvIII mutation with an expansion of CAR T cells and reduction in EGFRvIII expressing cells.

"These results highlight the potential for testing and treating glioblastomas with a personalized approach. The ultimate goal is to work towards a future where we can study a patient's organoid and test which CAR T cell is going to be the best against their tumor, in real time." O'Rourke said. "A shorter-term goal, given the heterogeneity of glioblastomas, is that in vitro testing of various therapeutic options may also help refine patient enrollment in clinical trials, by more accurately defining mutations and selecting the appropriate, available targeted therapies for each."

Credit: 
University of Pennsylvania School of Medicine

NASA-NOAA satellite finds development of Tropical Cyclone Sarai

image: NASA-NOAA's Suomi NPP satellite passed over the Southern Pacific Ocean on Dec. 26 and found Tropical Storm Sarai had developed near Fiji. The image showed strong bands of thunderstorms from the western quadrant wrapping into the low-level center of circulation.

Image: 
NASA Worldview, Earth Observing System Data and Information System (EOSDIS)

Imagery from NASA-NOAA's Suomi NPP satellite showed that a tropical low-pressure area has consolidated and organized in the Southern Pacific Ocean near Fiji.

Tropical Storm Sarai has formed to the west of Fiji. Fiji is an archipelago, consisting of more than 300 islands in the South Pacific Ocean.

On Dec. 26 at 6:43 a.m. EST) Dec. 27 at 12:43 a.m. Fiji local time, the Fiji Meteorological Service has issued various warnings for Fiji and surrounding islands. A gale warning remains in force for Rotuma, Vanua Levu, Taveuni and nearby smaller islands, Yasawa and Mamanuca Group, Kadavu, Lomaiviti group, Viti Levu and nearby smaller islands. A strong wind warning remains in force for the rest of Fiji. A heavy rain warning remains in force for the Fiji group.

The Visible Infrared Imaging Radiometer Suite (VIIRS) instrument aboard Suomi NPP provided a visible image of Sarai that revealed a band of thunderstorms were wrapping into the low-level center of circulation.

At 4 a.m. EST (0900 UTC) on Dec. 26, the Joint Typhoon Warning Center or JTWC in Pearl Harbor, Hawaii noted that Sarai had maximum sustained winds near 35 knots (40 mph/65 kph). Sarai was located near latitude 13.7 degrees south and longitude 176.2 degrees east, approximately 320 nautical miles north-northwest of Suva, Fiji. The tropical cyclone has tracked south southeastward. The tropical storm's center is expected to stay over water, just southwest of Fiji. JTWC said, "The favorable environment will allow steady 'intensification to 65 knots as it passes Nadi."

Tropical cyclones and hurricanes are the most powerful weather events on Earth. NASA's expertise in space and scientific exploration contributes to essential services provided to the American people by other federal agencies, such as hurricane weather forecasting.

For updated forecasts from the Fiji Meteorological Service, visit: http://www.met.gov.fj/

Credit: 
NASA/Goddard Space Flight Center

NASA satellite tracks tropical storm Phanfone into the South China Sea

image: On Dec. 26, 2019, the MODIS instrument that flies aboard NASA's Terra satellite provided a visible image of Tropical Storm Phanfone re-strengthening in the South China Sea.

Image: 
NASA Worldview

Tropical Storm Phanfone brought typhoon-force winds and heavy rains across sections of the Philippines on Christmas Eve and Christmas day. Phanfone is known as Ursula in the Philippines. Now the storm has moved into the South China Sea and NASA's Terra satellite captured an image of the tropical cyclone.

Phanfone's maximum sustained winds peaked near 95 knots on Dec. 25 at 4 a.m. EST (0900 UTC) as it passed through the Philippine archipelago.

On Dec. 26, 2019, the Moderate Imaging Spectroradiometer or MODIS instrument that flies aboard NASA's Terra satellite provided a visible image of Phanfone that showed the storm maintained its circular shape after crossing the Philippines. A rounded shape of a tropical cyclone indicates an organized storm. The MODIS image revealed bands of thunderstorms spiraled into the low-level center of circulation.

At 10 a.m. EST (1500 UTC) on Dec. 26, the Joint Typhoon Warning Center noted that Tropical Cyclone Phanfone was located near latitude 14.0 degrees north and longitude 117.4 degrees east, about 554 nautical miles east-southeast of Da Nang, Vietnam. Maximum sustained winds were 75 knots (86 mph/139 kph). Phanfone is moving to the northwest.

Phanfone is forecast to begin a weakening trend and move toward Hainan Island, China. After two days, the storm is expected to weaken to a tropical depression.

NASA's Terra satellite is one in a fleet of NASA satellites that provide data for hurricane research.

Tropical cyclones and hurricanes are the most powerful weather events on Earth. NASA's expertise in space and scientific exploration contributes to essential services provided to the American people by other federal agencies, such as hurricane weather forecasting.

Credit: 
NASA/Goddard Space Flight Center

Can brain injury from boxing, MMA be measured?

MINNEAPOLIS -For boxers and mixed martial arts (MMA) fighters, is there a safe level of exposure to head trauma? A new study shows different effects in the brain for younger, current fighters compared to older, retired fighters. The study is published in the December 23, 2019, online issue of Neurology®, the medical journal of the American Academy of Neurology.

As a group, both the current and the former fighters had loss of brain volume. In the current fighters, the volume loss was in areas of the brain that suggest it is a result of the injury, when nerve fibers are torn as the brain shifts inside the skull. In the retired fighters, the volume loss was in areas of the brain that suggest it is due to the progressive disease process seen in neurodegenerative diseases such as chronic traumatic encephalopathy (CTE) or Alzheimer's disease.

CTE is a rare brain disease found in athletes and others with a history of repeated head traumas. Symptoms include memory loss and thinking problems as well as emotional and behavior changes such as aggression.

"More research is needed to confirm these findings and to see if this pattern of loss of brain volume continues over a longer time period, but the results suggest that people with repeated head impacts may experience different processes in the brain at different times," said study author Charles Bernick, MD, of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, and a member of the American Academy of Neurology. "Ideally, future studies would build on these results and help us identify ways to predict irreversible injury so we could reduce the risks for these professional athletes before it's too late."

The study involved 50 current boxers with an average age of 29 and an average of five fights; 23 retired boxers with an average age of 45 and an average of 38 fights; and 100 mixed martial arts fighters with an average age of 29 and an average of eight fights. They were compared to 31 non-fighters with an average age of 31 who had no history of head trauma, military service or participation at the high school level or higher in a sport in which head trauma can often occur, such as football or soccer.

Bernick said too few retired MMA fighters took part in the study to form a group. He also noted that a few women were involved in the study: one retired boxer, two current boxers, 10 MMA fighters and five of the non-fighters.

The participants had brain scans and took tests of memory and thinking skills at the beginning of the study and again each year for at least two years.

Compared to the non-fighters, the current boxers had a greater average yearly rate of loss of brain volume in the areas of the left thalamus, the mid-anterior corpus callosum and the central corpus callosum. In the MMA fighters, a similar pattern was seen, but to a slightly lesser extent, in the left thalamus and the central corpus callosum, Bernick said.

For the left thalamus area of the brain, the average volume at the beginning of the study was 3,773 cubic millimeters. The current boxers lost an average of 145 cubic millimeters (mm3) in volume per year, compared to a loss of 100 mm3 for the MMA fighters and a gain of 43 mm3 for the non-fighters.

The retired boxers did not show changes in those areas of the brain. Instead, they showed brain volume loss in the areas of the left and right amygdala and the right hippocampus. These are areas of the brain that are affected in diseases such as Alzheimer's and CTE.

For the right hippocampus, the average volume at the start of the study was 2,350 mm3. The retired boxers lost an average of 43 mm3 per year, compared to a gain of 10 mm3 for the non-fighters.

Bernick noted that these changes in brain volumes were relatively small. "More research is needed to determine if these small changes could help us predict what will happen for individual athletes," he said.

Overall, the researchers found no significant differences in the scores on the thinking and memory tests among the groups of current and retired fighters and non-fighters. However, when they divided the current fighters into those who had brain volume loss and those without, they found that those with brain volume loss had worse scores on two of the thinking tests for processing speed.

One limitation of the study is that fighters volunteered to take part. So it is possible that people having problems or concerns about their health might be more likely to take part in the study.

Bernick has received research funding from Ultimate Fighting Championship (UFC), Top Rank Promotions, Haymon Boxing, Bellator/Spike TV and UCLA Dream Fund.

Credit: 
American Academy of Neurology

California's stricter vaccine exemption policy and improved vaccination rates

image: California's elimination, in 2016, of non-medical vaccine exemptions from school entry requirements was associated with an estimated increase in vaccination coverage at state and county levels.

Image: 
kfuhlert, Pixabay

California's elimination, in 2016, of non-medical vaccine exemptions from school entry requirements was associated with an estimated increase in vaccination coverage at state and county levels, according to a new study published this week in PLOS Medicine by Nathan Lo of the University of California, San Francisco, and colleagues.

Vaccine hesitancy, the reluctance or refusal to receive vaccinations, is a growing public health problem in the United States and globally. The effectiveness of state policies that eliminate non-medical exemptions to childhood vaccination requirements has been unclear. In the new study, researchers used publicly available data from the US Centers for Disease Control and Prevention on coverage of measles, mumps, and rubella (MMR) vaccination and rates of both non-medical and medical exemptions in children entering kindergarten. The dataset included information on 45 states from 2011 to 2017 and county-level data from 17 states spanning 2010 through 2017.

The results of the analysis suggest that after the 2016 implementation of California's new exemption policy, MMR coverage in California increased by 3.3% over what the projected MMR coverage in California would be in the absence of the policy. Non-medical vaccination exemptions decreased by 2.4% and medical exemptions increased by 0.4%. Change in MMR vaccination coverage across California counties from 2015 to 2017 ranged from a 6% decrease to a 26% increase, with the largest increases seen in "high risk" counties with the lower pre-policy vaccination coverage.

"These study results support the idea that state level governmental policies to remove non-medical exemptions can be effective strategies to increase vaccination coverage across the United States," the authors say.

Credit: 
PLOS