Culture

How plants are built to be strong and responsive

image: Microtubules - guiding role in organising cellulose.

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John Innes Centre

Organised cellulose fibres allow plants to grow, support themselves and store fixed carbon from the atmosphere. Wood and dietary fibre is largely made of cellulose, and coal is derived from cellulose synthesised millions of years ago.

Researchers have solved the long-standing mystery of how plants control the arrangement of their cellulose fibres.

Previous studies have shown that microtubules - hollow tubes with a diameter one thousandth of a human hair - play a key role in organising cellulose synthesis. They do this by guiding cellulose synthase complexes (CSCs) - nanomachines that spin cellulose fibres out while travelling along the cell membrane.

But when microtubules are removed by drugs, CSCs continue to journey in an organised way, suggesting another mechanism is at play.

In this study, which appears in the journal Current Biology, researchers at the John Innes Centre, discover this mechanism.

By slowing down microtubules inside growing leaves, spacing them apart and removing them altogether in some experiments, they reveal a system that can independently guide CSCs.

In this system CSCs interact with the cellulose trails left by other complexes, like ants following the chemical trails left by other ants.

Further investigation reveals this autonomous system can be overridden by microtubule guidance, allowing the 'ant columns' to be redirected in response to environmental and developmental cues.

Together the findings reveal that plants have a dual guidance system to organise their cellulose fibres.

The study concludes that having a dual guidance may provide a general mechanism to ensure both strong coherence and flexibility of response to environmental and developmental cues, allowing effective regulation of the growth and strength of cell walls.

"The mechanism we discovered was not predicted," says lead author Dr Jordi Chan. "We hope our findings will help scientists interested in how plants build themselves and those interested in applying this knowledge for sustainable crop productivity and environmental protection."

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John Innes Centre

What interventional radiologists need to know about frostbite and amputation

image: DSA image obtained approximately 24 hours after 1 mg/h IA tPA infusion, 500 U/h heparin via peripheral IV, and daily oral aspirin (81 mg) shows improved perfusion of digital arteries, albeit with suboptimal vascular blush of distal second and third phalanges.

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American Journal of Roentgenology (AJR)

Leesburg, VA, February 6, 2020--An ahead-of-print article in the April issue of the American Journal of Roentgenology (AJR) reviewing various techniques and clinical management paradigms to treat severe frostbite injuries--relevant for interventional radiologists, especially--showed promising results using both intraarterial (IA) and IV tPA (tissue plasminogen activator) to reduce amputation.

"Severe frostbite injuries can lead to devastating outcomes with loss of limbs and digits, yet clinical management continues to consist primarily of tissue rewarming, prolonged watchful waiting, and often delayed amputation," wrote Boston Medical Center radiologists John Lee and Mikhail Higgins.

A search of the literature by Lee and Higgins yielded 157 citations. After manually screening for inclusion criteria of case reports, case series, cohort studies, and randomized prospective studies that reported the use of tPA to treat severe frostbite injuries, 16 qualified for review.

Lee and Higgins' analyzed series included 209 patients with 1109 digits at risk of amputation treated with IA or IV tPA--116 and 77 patients, respectively. A total 926 at-risk digits were treated with IA tPA and resulted in amputation of 222 digits, for a salvage rate of 76%. Twenty-four of 63 patients underwent amputation after IV tPA, resulting in a 62% salvage rate.

Both digital subtraction angiography (DSA) and triple-phase bone scan were utilized for initial imaging evaluation of patients with severe frostbite injuries.

Additional concurrent treatment included therapeutic heparin at 500 U/h, warfarin with target international normalized ratio of 2:3, nonsteroidal anti-inflammatory drugs, pain management, and light dressings with topical antimicrobial agents.

"For many years," Lee and Higgins concluded, "the axiom 'frostbite in January, amputate in July' was an accurate description of the common outcome in frostbite injuries. Through a meta-analysis of thrombolytic therapy in the management of severe frostbite, this article provides a useful guideline for interventional radiologists, including a suggested protocol, inclusion and exclusion criteria, and potential complications."

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American Roentgen Ray Society

'Fluorescent markers' to illuminate cancer begins Phase 3 clinical trials

image: A Purdue discovery being developed by On Target Laboratories Inc., illuminates lung cancer cells on a patient during surgery. The 'fluorescent markers' help medical professionals identify and remove cancer cells during surgery and is shown to improve outcomes. The technology is beginning Phase 3 clinical trials.

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On Target Laboratories

On Target Laboratories Inc., a privately held biotechnology company developing the use of Purdue University-discovered fluorescent markers to target and illuminate cancer during surgery, has announced the results of a multi-institutional Phase 2 clinical trial in which outcomes were improved for 26% of patients undergoing pulmonary resection for non-small-cell lung cancer (NSCLC).

The results of the treatment, called OTL38, were presented at the 56th annual Meeting of the Society of Thoracic Surgeons (STS), held last month in New Orleans, and were featured in a plenary session as a J. Maxwell Chamberlain Memorial Paper for General Thoracic Surgery, considered to be among the top-rated abstracts at STS. The treatment was developed in the Purdue laboratory of Philip Low in the Purdue Institute of Drug Discovery. Low is the Presidential Scholar for Drug Discovery and Ralph C. Corley Distinguished Professor of Chemistry-Biochemistry in the Department of Chemistry. Currently, there are 288 clinical trials performed or in process using Purdue-developed medical treatments at 4,841 sites across the globe.

"Our goal is to provide surgeons with new technology to help them provide a more complete resection to more patients. This gives patients the best chance of improved outcomes after surgery," said Christopher Barys, president and CEO of On Target Laboratories.

Lung cancer is the leading cause of cancer-related deaths in the United States. Pulmonary resection, either a wedge resection, segmentectomy, or lobectomy, is recommended for most patients who have operable stage I-II non-small cell lung cancer. Intraoperative molecular imaging (IMI) -- also referred to as fluorescence-guided surgery -- may increase the likelihood of a more complete surgical resection, which could translate into increased survival for patients and reduced re-operations or adjuvant treatment for hospitals.

Conducted over 18 months, the study included 92 patients eligible for analysis. There were no drug-related serious adverse events and 24 patients, or 26%, were impacted during pulmonary resection, with 8% of patients having a change in their stage due to the use of IMI.

The study showed that IMI improved localization of small and peripheral lesions, which can be difficult for surgeons to identify visually or through manual palpitation, and enabled localization of otherwise unlocalizable lesions in 11 patients, or 12%. Further, 10 additional cancers were found in seven patients, or 8%. During the Specimen Check Phase, when the surgeon confirms that the nodule is in the specimen and analyzes the margins, surgeons thought all margins were adequate, yet back-table inspection using IMI revealed inadequate margins in eight patients, or 9%.

"OTL38 is the first technique that is specific to imaging adenocarcinomas of the lung, which is one of the most common types of invasive lung cancer," said Dr. Inderpal (Netu) S. Sarkaria of the Department of Cardiothoracic Surgery at the University of Pittsburgh Medical Center.

"Near-infrared imaging with OTL38 may be a powerful tool to help surgeons significantly improve the quality of lung cancer surgery by more clearly identifying tumors and allowing the surgeon to better see and completely remove them -- one of the most vital components in the overall care of patients with this disease."

OTL38 is under development in two Phase 3 clinical trials for lung and ovarian cancer indications. Both trials are being conducted under a special protocol agreement with the U.S. Food and Drug Administration. OTL38 also has received a fast-track designation for both the lung and ovarian cancer indications and an orphan designation for ovarian cancer from the FDA.

Low is a co-founder of On Target and the technology is licensed through the Purdue Research Foundation Office of Technology of Commercialization. The Purdue Institute of Drug Discovery is situated near Discovery Park District, a $1 billion-plus long-term enterprise to support a transformational center of innovation on the western edge of the Purdue University campus. The district includes the Convergence Center for Innovation and Collaboration, where startups, entrepreneurs, innovators and companies can collaborate with Purdue to address global challenges in health, sustainability, IT and space. The district already includes a public airport with a 7,000-foot runway, and partnerships with international companies including Rolls-Royce, Schweitzer Engineering Laboratories and Saab. Visit Discovery Park District.

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Purdue University

Popularity distance between a restaurant's location and a person's hometown biases ratings

CATONSVILLE, MD, February 6, 2020 - Product reviews and ratings have a strong impact on consumer consideration. In restaurant reviews, new research upcoming in the INFORMS journal Information Systems Research shows that location bias, based on the popularity difference between the reviewer's hometown and the distance to their destination, can affect a reviewers online rating by as much as 11%.

The study, "Your Hometown Matters: Popularity-Difference Bias in Online Reputation Platforms," conducted by Marios Kokkodis of Boston College and Theodoros Lappas of Stevens Institute of Technology, found when reviewers travel to a less popular location than their hometown, they review with a negative tendency. When reviewers travel to a more popular location than their hometown they review with a positive tendency.

In this study, Kokkodis and Lappas analyzed more than 760,000 restaurant reviews from nearly 1,500 cities in the continental U.S. In that dataset alone they said bias affected 98% of the restaurants.

"This effect on ratings alters the probability that an average customer will consider a restaurant by up to 16%. This is because the bias can distort online reputations, leading to misrepresented businesses and misinformed users," said Kokkodis, a professor in the Carroll School of Management at Boston College.

Awareness of the popularity-difference bias allows managers to improve the design of their ranking systems. The study shows such improvements can lead to up to 12% higher reviewer satisfaction and up to 24% more diversified top-restaurant recommendations.

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Institute for Operations Research and the Management Sciences

UNH researchers find synchronization of memory cells critical for learning and forming memories

image: On the left is an enlarged image showing many hippocampal neurons, most of which are silent and only a few are active. On the right are close ups of three highly active neurons, or memory cells, which become synchronized after memory formation (images modified from Zhou et al., 2020 FASEB Journal).

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UNH

DURHAM, N.H. - The phrase "Pavlov's dogs" has long evoked images of bells, food and salivating dogs. Even though this tried-and-true model of repetitive patterns mimics a variety of learning processes, what happens on a cellular level in the brain isn't clear. Researchers at the University of New Hampshire took a closer look at the hippocampus, the part of the brain critical for long-term memory formation, and found that the neurons involved in so-called Pavlovian learning shift their behavior during the process and become more synchronized when a memory is being formed - a finding that helps better understand memory mechanisms and provides clues for the development of future therapies for memory-related diseases like dementia, autism and post-traumatic stress disorder (PTSD).

"There are tens of millions of neurons in the hippocampus but only a small fraction of them are involved in this learning process" said Xuanmao (Mao) Chen, assistant professor of neurobiology. "Before engaging in Pavlovian conditioning, these neurons are highly active, almost chaotic, without much coordination with each other, but during memory formation they change their pattern from random to synchronized, likely forging new connecting circuits in the brain to bridge two unrelated events.

In the study, recently published in The FASEB Journal, researchers looked at Pavlovian learning patterns, or respondent conditioning, in mice. In the beginning, before any repetitive learning exercises, the mice did not know what to expect and using special imaging with an endomicroscope the researchers saw that the neural activity was disorderly. But after repeating different tasks associated with a conditional stimulus, like a tone or bell, the mice began to recognize the pattern and the highly active neurons became more synchronized. The researchers hypothesize that without forming synchronization, animals cannot form or retrieve this type of memory.

In the 1890's, Russian psychologist, Ivan Pavlov discovered classical conditioning through repetitive patterns of bell ringing which signaled to his dogs that food was on its way and stimulated salivation. This same learned behavior is important for episodic knowledge which is the basis for such things as learning vocabulary, textbook knowledge, and memorizing account passwords. Abnormal learning processing and memory formation are associated with a number of diseases like dementia, autism, and PTSD. People who struggle with these cognitive dysfunction-related disorders may have trouble retaining memories or can even form too strong a memory, as with PTSD patients. The UNH researchers believe that understanding the fundamentals of how classical conditioning shape neural connections in the brain could speed up the development of treatments for these disorders in the future.

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University of New Hampshire

Breathing may change your mind about free will

Have you ever gone ahead and eaten that piece of chocolate, despite yourself?

Do you inadvertently make decisions because you are hungry or cold? In other words, does the brain's processing of internal bodily signals interfere with your ability to act freely?

This line of thinking is at the heart of research that questions our ability to act on thoughts of free will. We already know that inner body signals, like the heartbeat, affect our mental states, can be used to reduce the perception of pain and are of fundamental importance for bodily self-consciousness.

Thanks to a new discovery, it turns out that these inner body signals do indeed affect acts of volition.

Scientists at EPFL in Switzerland have shown that you are more likely to initiate a voluntary decision as you exhale. Published in today's issue of Nature Communications, these findings propose a new angle on an almost 60-year-old neuroscientific debate about free will and the involvement of the human brain.

"We show that voluntary action is indeed linked to your body's inner state, especially with breathing and expiration but not with some other bodily signals, such as the heartbeat," explains Olaf Blanke, EPFL's Foundation Bertarelli Chair in Cognitive Neuroprosthetics and senior author.

At the center of these results is the readiness potential (RP), a signal of brain activity observed in the human cortex that appears not only before voluntary muscle movement, but also before one becomes aware of the intention to move. The RP is the signature of voluntary action since it consistently appears in brain activity measurements right before acts of free will (like being aware that one wants to reach for the chocolate).

Interpretations of the RP have been debated for decades. Some interpret the RP to show that free will is an illusion, since the RP precedes the conscious experience of free will. It seems to show that the brain commits to a decision (chocolate) before we are even consciously aware of having made that decision. [See box The readiness potential and interpretations.]

More recently, it was suggested that the RP could be an artefact of measurement, potentially putting free will back into our command.

But if we take on the view that our conscious decisions arise from a cascade of firing neurons, then the origin of the RP may actually provide insight into the mechanisms that lead to voluntary action and free will. The way the brain's neurons work together to come to a decision is still poorly understood. [See hidden patterns of brain activity unveiled by higher dimensional algebraic topology.] Our conscious experience of free will, our ability to make decisions freely, may then be intricately wired to the rest of our body. [See box Acts of free will and inner states of the body]

The EPFL results suggest that the origin of the RP is linked to breathing, providing a new perspective on experiences of free will: the regular cycle of breathing is part of the mechanism that leads to conscious decision-making and acts of free will. Moreover, we are more likely to initiate voluntary movements as we exhale. (Did you reach for that piece of chocolate during an exhale?)

These findings suggest that the breathing pattern may be used to predict 'when' people begin voluntary action. Your breathing patterns could also be used to predict consumer behavior, like when you click on that button. Medical devices that use brain-computer interfaces could be tuned and improved according to breathing. The breathing-action coupling could be used in research and diagnostic tools for patients with deficits in voluntary action control, like obsessive compulsive disorders, Parkinson disease, and Tourette syndromes. Blanke and Hyeong-Dong Park, first author of this research, have filed a patent based on these findings.

Free will hijacked by interoceptive signals?

More generally, the EPFL findings suggest that acts of free will are affected by signals from other systems of the body. Succumbing to that urge to eat chocolate may depend more on your body's internal signals than you may realize!

Blanke elaborates, "That voluntary action, an internally or self-generated action, is coupled with an interoceptive signal, breathing, may be just one example of how acts of free will are hostage to a host of inner body states and the brain's processing of these internal signals. Interestingly, such signals have also been shown to be of relevance for self-consciousness."

You may be tempted to blame acts of chocolate binging on interoceptive electrical signals hijacking your free will. The gut-mind connection is an active field of research and interoceptive messages sent to the brain certainly impact food cravings. For now, this latest EPFL research only improves predictions of when you will indulge in that craving, and not what you actually crave.

Acts of free will and inner states of the body

The prevailing view in neuroscience is that consciousness is an emergent phenomenon of the brain. Firing of the brain's neurons leads to consciousness and the feeling of free will or voluntary action. By belonging to the physical universe, the brain's electrical activity within the constraints of anatomy, is subject to the laws of physics. In this sense, brain signals encoding the body, lungs and heart might naturally affect the brain's cognitive states too and therefore influence acts of free will.

To test whether the RP depends on the body's inner state and the brain's representation thereof, Blanke and colleagues asked 52 subjects to press a button at will at Campus Biotech in Geneva. EEGs monitored brain activity, a belt around the chest measured breathing activity and cardiac activity was recorded.

The scientists found that the RP and voluntary action (pressing the button) is linked to the body's inner state - the regular breathing cycle - but not to the heartbeat. Participants initiated voluntary movements more frequently during an exhale than an inhale and were completely unaware of this breathing-action coupling. The RP was also modulated depending on the breathing cycle.

EPFL scientist and first author of the study Hyeong-Dong Park explains, "The RP no longer corresponds only to cortical activity 'unconsciously preparing' voluntary action. The RP, at least partly, reflects respiration-related cortical processing that is coupled to voluntary action. More generally, it further suggests that higher-level motor control, such as voluntary action, is shaped or affected by the involuntary and cyclic motor act of our internal body organs, in particular the lungs. Still the precise neural activity that controls breathing remains to be mapped."

The readiness potential and interpretations

Philosophers, psychologists, and more recently neuroscientists have long debated our ability to act freely. The meaning of the readiness potential (RP) has been questioned ever since its discovery by neuroscientists Hans Helmut Kornhuber and Lüder Deecke in 1965, and later regarding its relation to free will in neuroscientist Benjamin Libet's experiments.

The entire brain consists of approximately 100 billion neurons, and each individual neuron transmits electrical signals as the brain works. Electrodes placed on the head can measure the collective electrical activity of the brain's neurons, seen as wavy lines called an electroencephalogram (EEG).

In 1965, neuroscientists Hans Helmut Kornhuber and Lüder Deecke conducted a seminal experiment to test voluntary action and discovered a recurring pattern of brain activity. They placed EEG electrodes on top of the subject's head, and asked the subject to press a button at will. Kornhuber and Deecke discovered that the EEG consistently exhibited a rising slope of wavy lines, the readiness potential, 1 second or more before voluntary movement.

In the early 1980s, neuroscientist Benjamin Libet further tested the relationship between the RP and conscious awareness or intention of voluntary action. His highly influential results showed that approximately 200ms before his subjects pressed the button, they were aware of an urge or the intention to act, something Libet referred to as the W time, and yet the RP consistently preceded W time.

Libet suggested that these findings showed that even before we make a conscious decision of voluntary action, the brain was already unconsciously activated and involved in planning the action.

Some have interpreted the relation between the RP and W time as an indication that human free will might be an illusion. The RP is viewed as the brain committing to a decision (to press the button) before the subject is even aware of having made that decision. If commitment to a decision is being made before we are even aware of it, then what mechanism is making the decision for us?

For the neuroscientist who considers consciousness to arise from brain activity (versus brain activity arising from consciousness), Libet's results may not surprising, since the conscious experience of free will is viewed as an emergent phenomenon of brain activity.

Yet, Libet's results are in conflict with the notion of free will and voluntary action in philosophy of the mind, in folk psychology, in culture, and in legal matters.

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Ecole Polytechnique Fédérale de Lausanne

An invasive flatworm from Argentina, Obama nungara, found across France and Europe

image: Obama nungara.

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Photo by Pierre Gros

One of the consequences of globalization is the inadvertent human-mediated spread of invasive species. The presence of a new invader, named Obama nungara, is reported in France by an international team led by Jean-Lou Justine of ISYEB (Muséum National d'Histoire Naturelle, Paris, France). This is the first study of this invasion, reported in an article published in the open-access journal PeerJ.

As is the case for other land planarians including the New Guinea flatworm, Platydemus manokwari, and giant hammerhead flatworms from Asia, already reported in France, the origin of the invasion by O. nungara is likely to be via the international trade of plants, since adult planarians and cocoons can easily travel in potted plants. However, in contrast to the previously recorded species of land planarians that have been found only in a limited part of the country, the flatworm Obama nungara is reported from an area representing three quarters of metropolitan France.

Land flatworms are predators of soil animals, including earthworms and molluscs, and thus are a possible threat to the biodiversity of native animals and to soil ecology, although the ecological impact has yet to be studied.

To date, the presence of Obama nungara has been occasionally recorded from several countries in Europe, including Spain, Portugal, UK, Italy, and Belgium. However, in none of these countries has a study of the extent of the occurrence of O. nungara been performed.

Observations in France, mainly based on citizen science, include 530 verified records received from 2013 to 2018. Results show that the species is now present in 72 of the 96 Departments of Metropolitan France, an area representing 75% of the country. The species is especially abundant in gardens along the Atlantic coast and the Mediterranean coast. The species has also been recorded on Corsica in the Mediterranean Sea. Most records were from a low altitude, and there are no records of the species from mountainous regions such as the Alps, Pyrenees and Massif Central. New records from Italy and Switzerland are also included in the study.

Molecular studies, based on the Cytochrome Oxidase Type 1 sequences, show that Obama nungara has three populations: two in Argentina and one in Brazil. Only one of these populations, "Argentina 1" in the paper, is present in Europe, including all France, and Spain, Portugal, UK, Italy, Belgium, and Switzerland. The population from Brazil has not reached Europe; Argentina is the sole source of this invasive species in Europe.

The extensive distribution of the species and its reported local abundance, combined with its predatory character, make Obama nungara a potential threat to the biodiversity and ecology of the soils in Europe. The authors estimate that O. nungara is the most threatening species of all invasive land planarians present in Europe.

In a climate of open science, the database of citizen science records and the molecular matrix are made public together with the paper. The authors mention that citizen science was extremely useful for evaluating the invasion, but urge to consider possible bias in the records, due to media coverage. Mention of land flatworms in the media immediately produced bursts of records, therefore hampering a correct analysis of the abundance of the species over time. It is expected that this new paper will encourage new records of Obama nungara from members of the public, not only in France but possibly other countries.

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PeerJ

All women should be educated after childbirth about high blood pressure

GRAPEVINE, Texas -- After childbirth, it is not uncommon for women to experience high blood pressure. If not treated, it can have serious consequences, including stroke and, in some cases, death. It is unclear what causes high blood pressure after childbirth, or who may develop it.

In a study to be presented today at the Society for Maternal-Fetal Medicine's (SMFM) annual meeting, The Pregnancy Meeting™, researchers will unveil findings that suggest all women, regardless of whether they have a history of high blood pressure, need to be educated about the signs and symptoms of high blood pressure, also known as postpartum hypertension.

The study looked at 164 women from September 2016 to July 2019 who gave birth at Children's Memorial Hermann Hospital in Houston and were readmitted with high blood pressure. The majority of women (64.6%) were readmitted within seven days, and 39 percent of those women were not diagnosed with high blood pressure prior to being discharged.

"Texas has one of the highest maternal mortality rates in the nation. As clinicians, we're always looking for ways to tailor interventions so we can reduce deaths," said the study's lead author Conisha Holloman, MD, a maternal-fetal medicine fellow with McGovern Medical School at UTHealth in Houston. "At our hospital, we noticed a lot of women were being readmitted after giving birth with high blood pressure, even when they didn't have a history of high blood pressure. While clearly more research needs to be done on what causes high blood pressure after childbirth, what our study reveals is a strong need to educate all women ? not just those who may be at a higher risk -- about the signs and symptoms of high blood pressure before they are discharged."

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Society for Maternal-Fetal Medicine

Oh my aching back: Do yoga, tai chi or qigong help?

image: People with chronic low back pain are at increased risk of functional limitations, job-related disability, and potential long-term disability. Moreover, the economic burden of chronic low back pain is high due to the cost of medications such as opioids, procedures, hospitalization, surgical treatment, and absence from work.

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Florida Atlantic University

It's a pain. About 80 percent of adults in the United States will experience lower back pain at some point. Treating back pain typically involves medication, including opioids, surgery, therapy and self-care options. Efforts to reduce opioid use and increase physically based therapies to reduce pain and increase physical function and safety are crucial.

Patients are often advised to use non-pharmacological treatments to manage lower back pain such as exercise and mind-body interventions. But, do they really help? In a review published in the journal Holistic Nursing Practice, researchers from Florida Atlantic University's College for Design and Social Inquiry and Christine E. Lynn College of Nursing evaluated the evidence of effects of three movement-based mind-body interventions on chronic low back pain. They examined yoga, tai chi, which combines gentle physical exercise and stretching with mindfulness, and qigong, a traditional Chinese meditative movement therapy focused on body awareness and attention during slow, relaxed, and fluid repetitive body movements. Little is known about the effects of movement-based mind-body intervention, in particular qigong and tai chi.

Researchers compared and contrasted yoga, tai chi and qigong by examining frequency and duration of these interventions; primary and secondary outcomes; attrition rates and possible adverse events; and results. Findings from their review provide empirical evidence regarding the benefits of yoga, tai chi, and qigong, which have been recommended by health care providers for patients with lower back pain.

"Back pain is a major public health issue often contributing to emotional distress such as depression and anxiety, as well as sleep issues and even social isolation," said Juyoung Park, Ph.D., corresponding author and an associate professor in the Phyllis and Harvey Sandler School of Social Work within FAU's College for Design and Social Inquiry. "We reviewed data to determine the effects of movement-based mind-body interventions on chronic back pain, psychological factors, coping strategies, and quality of life in people suffering with back pain. Our goal was to provide a comprehensive assessment of the effects of these interventions to be able to offer information across disciplines to implement evidence-based interventions to reduce such pain."

Of the 625 peer-reviewed articles the researchers identified, 32 met inclusion criteria and were included in the review. Results found that the majority of these articles showed movement-based mind-body interventions to be effective for treatment of low back pain, reporting positive outcomes such as reduction in pain or psychological distress such as depression and anxiety, reduction in pain-related disability, and improved functional ability. Among the key findings, researchers discovered that longer duration and high-dose yoga intervention showed reductions in back pain while tai chi reduced acute lower back pain in males in their 20s. Tai chi also was more effective than stretching for lower back pain in young males. In the general community, tai chi showed greater reductions in pain intensity, bothersomeness of pain symptoms, and pain-related disability than the control intervention. Because there are only three qigong studies to date, it was unclear to the researchers whether this intervention is useful in treating chronic lower back pain. Existing research suggests positive benefits of yoga, however, tai chi and qigong for lower back pain are still under-investigated.

"Two of the studies we examined in our review were focused on the effects of movement modality, specifically yoga, in veterans. Many military veterans and active duty military personnel experience chronic low back pain and are affected by this pain more than the general population," said Cheryl Krause-Parello, Ph.D., co-author, a professor and director of Canines Providing Assistance to Wounded Warriors (C-P.A.W.W.) within FAU's Christine E. Lynn College of Nursing, and a faculty fellow of FAU's Institute for Human Health and Disease Intervention (I-HEALTH). "Our review provides emerging evidence that movement-based mind-body interventions could benefit veterans and others experiencing chronic low back pain."

The review included both randomized and nonrandomized studies with a total of 3,484 subjects ages 33 to 73 years old. Study sample sizes ranged from 25 to 320 subjects. The majority of articles reported on yoga (25), followed by tai chi (four), and qigong (three). Most of the yoga studies were conducted in India, followed by the U.S., while other studies were conducted in Australia (tai chi) and Germany (qigong).

People with chronic low back pain are at increased risk of functional limitations, job-related disability, and potential long-term disability. Moreover, the economic burden of chronic low back pain is high due to the cost of medications such as opioids, procedures, hospitalization, surgical treatment, and absence from work.

"Yoga, tai chi and qigong could be used as effective treatment alternatives to pain medications, surgery, or injection-based treatments such as nerve blocks, which are associated with high incidence of adverse effects in treating lower back pain," said Park. "We need more clinical trials and empirical evidence so that clinicians can prescribe these types of interventions with more confidence for managing lower back pain in their patients."

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Florida Atlantic University

A new approach to calm that angry nose

image: Serum soluble SEMA4D levels were elevated in patients with ECRS and positively correlated with disease severity. Cell surface expression of SEMA4D on eosinophils from ECRS patients was reduced, which was due to MMP-9-mediated cleavage of membrane SEMA4D. Soluble SEMA4D induced eosinophil transendothelial migration. Treatment with anti-SEMA4D antibody ameliorated eosinophilic infiltration in sinus tissues.

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Osaka University

Osaka, Japan - Eosinophilic chronic rhinosinusitis (ECRS) is a type of airway disease involving nasal inflammation. Many studies have attempted to understand the molecular-based pathogenesis of recurrent ECRS; none have provided a clear explanation, until now.

In a new study published in The Journal of Allergy and Clinical Immunology, a team led by researchers from Osaka University investigated the activity of semaphorin protein, a cell-surface molecule that participates in nervous system signaling and immune responses. They found that semaphorin protein contributes to allergic reactions and development of nasal polyps in patients with ECRS.

In ECRS, inflammation leads to development of nasal polyps containing eosinophils (a subset of white blood cells). Treatment options include sinus surgery and systemic glucocorticoids. However, the effectiveness of these treatments can be insufficient and multiple side effects can occur. Thus, targeted molecular therapies may provide novel treatment options for patients with ECRS without these drawbacks. Because semaphorin has been identified in inflamed airway tissues, it is an attractive candidate for use in such therapies.

"In this study, we found that serum levels of semaphorin proteins were elevated in patients with ECRS, and that these levels were positively associated with multiple measures of disease severity," says Masayuki Nishide, corresponding author on the study. "We suspected that semaphorin protein played an important role in the pathogenesis of ECRS."

The Osaka University team found that activated eosinophils expressed high levels of semaphorin protein on the cell surface, which could be released into the surrounding environment through an enzymatic reaction. This soluble form of semaphorin protein could enable eosinophils to pass through endothelial cell lining, resulting in the onset of inflammation and formation of nasal polyps.

"Our analyses revealed that, in a mouse model of ECRS, mice without semaphorin protein had less nasal inflammation than normal mice, so we tested whether blocking semaphorin with an antibody could affect inflammation in normal mice with ECRS," says Takeshi Tsuda, lead author on the study. "As expected, we found that treatment with an anti-semaphorin antibody substantially reduced nasal inflammation in mice with ECRS."

Based on the results in the mouse model, the Osaka team concluded that anti-semaphorin antibody could provide a new treatment option for patients with ECRS. Additionally, the increased levels of semaphorin protein in patients with ECRS suggest that semaphorin protein can be used as a biomarker for ECRS in patients with nasal inflammation.

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Osaka University

The unchanging viscosity of cells

image: Viscosity is closely guarded within the cell, though at present we don't know who the guardians are.

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IPC PAS, Grzegorz Krzyzewski

The only thing that appears to be unchanging in living cells is that they are constantly changing. However, scientists from the IPC PAS have managed to show that there is a certain parameter that does not change. It's their viscosity. This research, although basic, may contribute to the development of completely new diagnostic and therapeutic methods.

It would seem that during the life of cells - DNA replication, protein formation, the constant changes in their quantity, metabolites, etc., such drastic transformations take place within them that the viscosity related to the ratio of water to the number of biological molecules in the cell should, (when looked at intuitively), change. This is what many scientists thought, including the authors of the paper published in Scientific Reports. "We wanted to examine how the viscosity of cytoplasm changes at various important moments in a cell's life, such as during division. That's why the result, i.e. the constancy of viscosity, was a complete surprise to us," says Dr Karina Kwapiszewska.

The measurement itself was a difficult and tedious process. A full cell cycle takes about 24 hours, and although cells can be synchronized like dancers in a ballet, i.e. made to all divide roughly at the same time, they cannot be persuaded to wait for an observer to take a picture of them. They constantly dance to their own inner music.

"Here a big nod to my colleague, Dr. Krzysztof Szczepa?ski, who spent more than one night carrying out fluorescence correlation spectroscopy measurements. They have to be performed every half hour during the whole cell cycle, and the cell won't wait until the morning to divide," says Dr Kwapiszewska. "Thanks to him and his perseverance we mapped the viscosity throughout the entire cycle. And that's with the right number of repetitions. This is the only way we could prove that what we measured was an actual parameter, not an artefact," she adds.

What's more, the IPC PAS scientists discovered that the cell's viscosity remains constant regardless of whether the cell comes from the lung or e.g. the liver, although these are very different tissues. And since it is constant, this means that the cell must need it to be so for a purpose. Especially since the size of cells can vary within a single population (e.g. skin cells) even ten-fold and this does not matter to them as much as their viscosity. So there must be a mechanism that regulates it.

The viscosity of a medium is undoubtedly very important for biochemical processes. Simply put, the higher the viscosity, the harder it is for particles to meet in order to react. Cells must actively regulate their viscosity otherwise reactions would be slower in some conditions and faster in others. And if one of the reactions were to slow down too much - the whole system could fall apart and the cell would never be able to restore its balance. "In one of our team's earlier papers (Soza?ski et. al., Phys Rev Lett 2015) it was shown that only a 6-fold increase in viscosity (this really isn't much) is sufficient to stop the entire active transport in a cell," explains Dr Kwapiszewska.

And here we come to the potential, though at present distant, applications of this discovery. Since an increase in viscosity inhibits life processes in the cell then perhaps this can be used, for example, to create therapeutics against cancer cells. The sort that would employ physical processes instead of, for example, inhibiting DNA replication.

"We also suspect that some neurodegenerative diseases may be caused by a local increase in viscosity in cells," says the author. "So, compensating for this could be a way to stop damage in Parkinson's or Alzheimer's disease and improve a patient's prognosis."

Now researchers want to find out how viscosity changes during cell death and whether this change in viscosity is the result or the cause of the process itself.

Credit: 
Institute of Physical Chemistry of the Polish Academy of Sciences

Global study maps cancer mutations in large catalogue

Mutations in 38 different types of cancer have been mapped by means of whole genome analysis by an international team of researchers from, amongst others, the University of Copenhagen, Aarhus University, Aarhus University Hospital, and Rigshospitalet. The researchers have compiled a catalogue of the cancer mutations that will be available worldwide to doctors and researchers.

Globally, cancer is one of the biggest killers and in 2018, an estimated 9.6 million people died of the disease. In order to provide the best treatment for the disease, it is essential to find out which mutations are driving the cancer.

In a major international collaboration called Pan-Cancer Analysis of Whole Genomes (PCAWG), researchers from the University of Copenhagen, Aarhus University, Aarhus University Hospital and Rigshospitalet have helped to map mutations in 38 different types of cancer.

The mutations have all been combined into a sort of catalogue. The catalogue, which is already available online, allows doctors and researchers from all over the world to look things up, consult with and find information about the cancer of a given patient.

'Most previous major studies have focused on the protein coding two percent of the genome. We have studied and analysed the whole genome, and our analyses of mutations that are affecting cancer genes have enabled us to genetically explain 95 percent of the cancer occurrences we have studied by means of mutations,' says co-author Joachim Weischenfeldt, Associate Professor at the Biotech Research & Innovation Centre, University of Copenhagen, and the Finsen Laboratory, Rigshospitalet.

'So, if you know which mutations have caused cancer, the so-called driver mutations, you will be able to better tailor a treatment with the most suitable drugs or design new drugs against the cancer. Precision medicine is completely dependent on the mapping of driver mutations in each cancer, in relation to diagnosis, prognosis and improved treatment,' says co-author Jakob Skou Pedersen, professor at Bioinformatics Research Centre and Department of Clinical Medicine, Aarhus University, and Aarhus University Hospital.

The new research results are published in a special edition of the scientific journal Nature with focus on PCAWG. To date, it is the largest whole genome study of primary cancer. This means that the analysis was performed based on material from the tissue in which the tumour originated and before the patient has received any treatment.

From a Handful to 100,000 Mutations

The researchers have mainly analysed and had data on the most common types of cancer such as liver, breast, pancreas and prostate cancer. In total, they have analysed whole genome-sequenced tumour samples from more than 2,600 patients.

Based on their analyses, they could see that the number of mutations in a cancer type varies a lot. Myeloid dysplasia and cancer in children have very few mutations, while there may be up to 100,000 mutations in lung cancer.

But even though the number of mutations spans widely, researchers could see that on average there were always 4-5 mutations that were driving the disease, the so-called drivers - no matter what type of cancer it was.

'It is quite surprising that almost all of them have the same number of driver mutations. However, it is consistent with theories that a cancerous tumour needs to change a certain number of mechanisms in the cell before things start to go wrong,' says Jakob Skou Pedersen.

In the catalogue, the researchers have divided the mutations into drivers and passengers. Driver mutations provide a growth benefit for the cancer, while passenger mutations cover all the others and are harmless. The vast majority of all mutations are passengers.

Genetics or Tissue

To store and process the vast amount of data, the research team has used so-called cloud computing, using 13 data centres spread across three continents. They have had centres in Europe, the US, and Asia.

The large data set has been necessary to establish what was common and unique to the different types of cancer. Today, cancer is divided according to the tissue in which the disease originates, for example breast, brain, and prostate.

The researchers found many things that were completely unique to each type of tissue. Conversely, they also found many common traits across the tissue types. According to Joachim Weischenfeldt, there is thus a need to rethink the way we think about cancer.

'Cancer is a genetic disease, and the type of mutations is often more important than where the cancer originates in the body. This means that we need to think of cancer not just as a tissue-specific disease, but rather look at it based on genetics and the mutations it has.'

'For example, we may have a type of breast cancer and prostate cancer where the driver mutations are similar. This means that the patient with prostate cancer may benefit from the same treatment as the one you would give the breast cancer patient, because the two types share an important driver mutation,' says Joachim Weischenfeldt.

Credit: 
University of Copenhagen - The Faculty of Health and Medical Sciences

Growing new blood vessels could provide new treatment for recovering movement

Many health conditions - ranging from disease of particular organs such as heart and lungs, widespread metabolic issues such as diabetes, or following trauma such as spinal cord injury - cause difficulties with movement. This can severely affect quality of life and new research published today in the Journal of Physiology highlights the link between loss of the smallest blood vessels in muscle and difficulties moving and exercising. Understanding this link opens up the possibility of aiding recovery by growing more blood vessels in your muscles.

When we are physically active, our heart and lungs increase the amount of oxygen in our blood that is delivered to our working muscles. Our capillaries, the smallest blood vessels, are the gateway between fuel supplied by the circulating blood and the demand generated within muscle cells. Therefore, in order for your muscles function properly, the capillaries need to be in good shape. Unfortunately, the consequence of many heath conditions is that the muscle loses capillaries and therefore movement becomes difficult.

Heavy smokers can suffer from 'smoker's leg', which is where arteries narrow and become blocked. An existing treatment for this is to widen blood vessels to improve circulation. However, this new research shows that more blood flow might not be the solution, and instead increasing the number of small blood vessels, i.e. capillaries, might be more helpful for recovering movement.

The researchers used a rat model of heart disease to study the effect of restricting the number of working capillaries in muscle on movement. Using an animal model was key because in humans you wouldn't be able to look at a change in just one consequence of the disease, as there are usually a number of problems evident at the same time.

Stuart Egginton from the University of Leeds, senior author on the study, said:

"By studying muscle we have isolated one of the complications found in many serious diseases, and found that increasing the number of small blood vessels is a new treatment option alongside the more traditional approach of widening large vessels. This research could help treat people suffering from difficulty moving, which is one of the most debilitating effects of heart disease or diabetes."

Credit: 
The Physiological Society

Direct synthesis of azulene continues to reveal alluring properties

image: The blue color is hard to observe in its crystal form. Azulene emits an odor resembling mothballs.

Image: 
Shinshu University

Azulene is a pretty neat substance. As the name suggests, it displays a peculiar blue color. First synthesized in the 1930s, azulene has been used in medicine for its bioactive properties. Now azulene derivatives are being studied for use in organic electronics such as n-type semiconductors, solar cells and non-linear optics. This is made possible by the functionalization of the azulene ring. Odd-positions of the ring had been researched extensively for their high reactivity, though it was hard to select their functionality due to their electronic properties. Highly functionalized azulenes were enabled by cross-coupling reactions of even-numbered positions of azulenes. However, it has been difficult to synthesize these precursors.

Associate Professor Taku Shoji at Shinshu University et al. was successful in direct synthesis of 2-arylazulene. One of the few researchers who specialize in azulene synthesis, Professor Shoji states that the breakthrough in this study allows for the synthesis of azulene on a gram-scale instead of milligrams. The previous possible production volume made it difficult for possible use in organic electronics. Being able to synthesize azulenes from readily available 2H-cyclohepta[b]furan-2-one derivatives and silyl enol ether is a great step forward in practical applications.

The fluorescence of the azulene derivatives in acidic conditions (which can be seen in the photo) was observed unexpectedly during this study. Though this property of azulene derivatives had been previously reported, the research group found that 2-phenylazulenes exhibit the emission in acidic media and the fluorescence wavelength depends on the electronic properties of the substituents on the substituted benzene ring. The group is collaborating with photochemical experts to elucidate the mechanism of this unexpected fluorescence.

Professor Shoji and his team continue to attempt to synthesize 2-arylazulene at a lower temperature using an appropriate catalyst. Professor Shoji states that "although azulene have been studied for a hundred years, new synthetic methods, reactivity and physical properties continue to be discovered." He remains fascinated by what this mysterious blue substance can reveal and ultimately be applied for.

Credit: 
Shinshu University

End-of life-care needs will nearly double over the next 30 years, highlighting urgent need for funding

New research at Trinity College Dublin, published today (Thursday, February 6th, 2020), shows that the number of people dying in Ireland with palliative care needs will increase 84% to 2046.

The study, conducted at Trinity's Centre for Health Policy and Management and The Irish Longitudinal study on Ageing (TILDA), estimated how many people will die from a serious disease such as cancer, heart disease, organ failure and dementia to 2046. The estimated 84% increase compares to 43% for England and Wales in a similar period.

Projected increases are underpinned by two factors of population ageing: increasing absolute numbers of people dying, and increasing proportion of people who experience a serious illness prior to death. Increases are most observable in the 85+ age group, which is growing rapidly. The difference with England primarily reflects Ireland's population, which is now younger than the EU average and so will have faster-growing needs in the 21st century.

Palliative care is a type of specialist supportive care that aims to improve quality of life for people living and dying with serious illness. It is provided in Ireland in hospitals, by homecare teams and at inpatient hospices.

Professor Karen Ryan, Consultant in Palliative Medicine at the Mater and St Francis Hospice, and Clinical Professor in the School of Medicine at UCD, said that the results indicate an urgent need to address funding and workforce in palliative care:

"Ireland is recognised to have a high standard of palliative care provision. Our data show that capacity must increase significantly if we are to maintain that.

People are living longer with more serious illnesses. This is a success story for society but also brings challenges.

Sláintecare priorities include a revised national palliative care policy in 2020 and we hope that our results will inform this review, so that people dying with serious illness and their families receive the care and support they need during this unique life event."

The study also estimated numbers of people who will live with serious illnesses requiring expert support in the years prior to death. They found that the number of people living with a serious disease outnumber those in the last year of life with a serious disease by about 12:1.

Dr Peter May, Research Assistant Professor in Health Economics at Trinity and lead author of the study, said that this has important implications also:

"Population ageing means not only more people dying with serious medical conditions but many more people living with them also.

The highest average illness burden and health care need is of course among those near the end of life. But total population needs will be driven by all people experiencing these conditions.

"Health care provision has to change to reflect those needs. We need better anticipatory and supportive care to lower avoidable hospital admissions and keep people living at home and in their communities for as long possible."

Credit: 
Trinity College Dublin