Date:
June 22, 2017

Source:
University of Kentucky

Summary:
A new study demonstrates a process with great potential for developing technologies for reducing CO2 levels.

 

This is the Cu2O (right) that gets photocorrosion compared to Cu2O/TiO2 (left) that operates under a Z-scheme to reduce CO2.
Credit: Ruixin Zhou, UK doctoral student of chemistry.

 

 

A team of chemists from the University of Kentucky and the Institute of Physics Research of Mar del Plata in Argentina has just reported a way to trigger a fundamental step in the mechanism of photosynthesis, providing a process with great potential for developing new technology to reduce carbon dioxide levels.

Led by Marcelo Guzman, an associate professor of chemistry in the UK College of Arts and Sciences, and Ruixin Zhou, a doctoral student working with Guzman, the researchers used a synthetic nanomaterial that combines the highly reducing power of cuprous oxide (Cu2O) with a coating of oxidizing titanium dioxide (TiO2) that prevents the loss of copper (I) ion in the catalyst. The catalyst made of Cu2O/TiO2 has the unique ability to transfer electrons for reducing the atmospheric greenhouse gas carbon dioxide (CO2) while simultaneously breaking the molecule of water (H2O). The unique feature of this catalyst for electron transfer mimics the so called “Z-scheme” mechanism from photosynthesis.

Published in Applied Catalysis B: Environmental, the researchers demonstrated that if the catalyst is exposed to sunlight, electrons are transferred to CO2 in a process that resembles the way photosystems 1 and 2 operate in nature.

“Developing the materials that can be combined to reduce CO2through a direct Z-scheme mechanism with sunlight is an important problem,” said Zhou. “However, it is even more difficult to demonstrate the process actually works. From this scientific viewpoint, the research is contributing to advance feature technology for carbon sequestration.”

This is a task that many scientists have been pursuing for a long time but the challenge is to prove that both components of the catalyst interact to enable the electronic properties of a Z-scheme mechanism. Although a variety of materials may be used, the key aspect of this research is that the catalyst is not made of scarce and very expensive elements such as rhenium and iridium to drive the reactions with sunlight energy reaching the Earth’s surface. The catalyst employed corrosion resistant TiO2 to apply a white protective coating to octahedral particles of red Cu2O.

The team designed a series of experiments to test out the hypothesis that the catalyst operates through a Z-scheme instead of using a double-charge transfer mechanism. The measured carbon monoxide (CO) production from CO2reduction, the identification of hydroxyl radical (HO* ) intermediate from H2O oxidation en route to form oxygen (O2), and the characterized electronic and optical properties of the catalyst and individual components verified the proposed Z-scheme was operational.

The next goal of the research is to improve the approach by exploring a series of different catalysts and identify the most efficient one to transform CO2 into chemical fuels such as methane. This way, new technology will be created to supply clean and affordable alternative energy sources and to address the problem of continuous consumption of fossil fuels and rising levels of greenhouse gases.


Story Source:

Materials provided by University of KentuckyNote: Content may be edited for style and length.


Journal Reference:

  1. Matías E. Aguirre, Ruixin Zhou, Alexis J. Eugene, Marcelo I. Guzman, María A. Grela. Cu 2 O/TiO 2 heterostructures for CO 2 reduction through a direct Z-scheme: Protecting Cu 2 O from photocorrosionApplied Catalysis B: Environmental, 2017; 217: 485 DOI: 10.1016/j.apcatb.2017.05.058

 

Source: University of Kentucky. “Catalyst mimics the z-scheme of photosynthesis.” ScienceDaily. ScienceDaily, 22 June 2017. <www.sciencedaily.com/releases/2017/06/170622143047.htm>.

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Date:
June 21, 2017

Source:
Louisiana State University

Summary:
Floods are the natural disaster that kill the most people. They are also the most common natural disaster. As the threat of flooding increases worldwide, a group of scientists have gathered valuable information on flood hazard, exposure and vulnerability in counties throughout the US.

 

Thousands of homes were devastated by flooding in inland communities in Louisiana in August 2016.
Credit: Nina Lam, LSU

 

 

Floods are the natural disaster that kill the most people. They are also the most common natural disaster. As the threat of flooding increases worldwide, a group of scientists at LSU have gathered valuable information on flood hazard, exposure and vulnerability in counties throughout the U.S. They studied development trends from 2001 to 2011 and found that urban development has declined in coastal flood zones in general across the U.S. However, development in flood zones in inland counties has grown. These results and more have been published in the Annals of the American Association of Geographers.

“We found more urban development in the inland flood zones than the coastal areas between 2000-2011, which is a worrisome trend. The implications are that people living in the coastal zone want to migrate inland, but don’t realize they are still vulnerable if they live in the flood zones in inland areas,” said Nina Lam, LSU professor of Environmental Sciences in College of the Coast & Environment and co-author of the study.

This alarming trend may point to a need for more awareness, education and communication about flood risk in inland counties, said the researchers. More affordable housing in non-flood zones and strategies to mitigate floods are also needed inland.

“The results show that people in coastal areas are more aware of flood threats than those living in inland flood zones, and that populations in inland areas are increasing. This information could aid future flood-planning efforts in inland communities,” said Judy Skog, a director of the National Science Foundation’s Coastal SEES, or NSF’s sustainability program, which co-funded the research.

The researchers compiled urban development, flood hazard and census data and overlaid it on a map of the U.S. Although their analysis shows that Americans in general have become more aware of the risk of floods over the 10-year study period, the researchers identified several U.S. hot spots where urban development has grown in coastal flood zones including New York City and Miami.

The three counties in the U.S. that have the largest concentration of people living in a flood zone are located on the Gulf of Mexico. Cameron parish in Louisiana has 93.6 percent of its 6,401 population living in the flood zone, Monroe county in Florida has 91.4 percent of its 66,804 population and Galveston county in Texas has 82.8 percent of its 241,204 population living in a flood zone.

“This nationwide study of flood zones, human populations and urban development provides a tool that could be used globally,” Skog said.

Climate change, land subsidence and new levees and dams will change long-term flood exposure. Therefore, the accuracy of flood maps must be investigated.

“Flooding is the most common and widespread disaster we face nationally, and the one that is the easiest to alleviate by effective planning,” said Richard Yuretich, a director of NSF’s Dynamics of Coupled Natural and Human Systems, or CNH program, which co-funded the research. “This study provides important data on flood hazards across the country, and demonstrates that the research and education about floods that has been done over the past decade has helped manage risk. Yet there are still places where people are in harm’s way.”


Story Source:

Materials provided by Louisiana State UniversityNote: Content may be edited for style and length.


Journal Reference:

  1. Yi Qiang, Nina S. N. Lam, Heng Cai, Lei Zou. Changes in Exposure to Flood Hazards in the United StatesAnnals of the American Association of Geographers, 2017; 1 DOI: 10.1080/24694452.2017.1320214

 

Source: Louisiana State University. “Flooding risk: America’s most vulnerable communities.” ScienceDaily. ScienceDaily, 21 June 2017. <www.sciencedaily.com/releases/2017/06/170621114013.htm>.

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Neuroscientist explores the complex brain connections employed during word retrieval

Date:
June 19, 2017

Source:
San Diego State University

Summary:
How the brain narrows down a smorgasbord of related concepts to the one word you’re truly seeking is a complicated and poorly understood cognitive task. Looking at epilepsy patients who had a grid of electrodes directly atop their brains, researchers delved into this question and found that wide, overlapping swaths of the brain work in parallel to retrieve the correct word from memory.

 

Most adults can quickly and effortlessly recall as many as 100,000 regularly used words when prompted, but how the brain accomplishes this has long boggled scientists.
Credit: © BillionPhotos.com / Fotolia

 

 

When you look at a picture of a mug, the neurons that store your memory of what a mug is begin firing. But it’s not a pinpoint process; a host of neurons that code for related ideas and items — bowl, coffee, spoon, plate, breakfast — are activated as well. How your brain narrows down this smorgasbord of related concepts to the one word you’re truly seeking is a complicated and poorly understood cognitive task. A new study led by San Diego State University neuroscientist Stephanie Ries, of the School of Speech, Language, and Hearing Sciences, delved into this question by measuring the brain’s cortical activity and found that wide, overlapping swaths of the brain work in parallel to retrieve the correct word from memory.

Most adults can quickly and effortlessly recall as many as 100,000 regularly used words when prompted, but how the brain accomplishes this has long boggled scientists. How does the brain nearly always find the needle in the haystack? Previous work has revealed that the brain organizes ideas and words into semantically related clusters. When trying to recall a specific word, the brain activates its cluster, significantly reducing the size of the haystack.

To figure out what happens next in that process, Ries and colleagues asked for help from a population of people in a unique position to lend their brainpower to the problem: patients undergoing brain surgery to reduce their epileptic seizures. Before surgery, neurosurgeons monitor their brain activity to figure out which region of the brain is triggering the patients’ seizures, which requires the patients to wear a grid of dozens of electrodes placed directly on top of the cortex, the outermost folded layers of the brain.

While the patients were hooked up to this grid in a hospital and waiting for a seizure to occur, Ries asked if they’d be willing to participate in her research. Recording brain signals directly from the cortical surface affords neuroscientists like Ries an unparalleled look at exactly when and where neurons are communicating with one another during tasks.

“During that period, you have time to do cognitive research that’s impossible to do otherwise,” she said. “It’s an extraordinary window of opportunity.”

For the recent study, nine patients agreed to participate. In 15 minute-sessions, she and her team would show the patients an item on a computer screen — musical instruments, vehicles, houses — then ask them to name it as quickly as possible, all while tracking their brain activity.

They measured the separate neuronal processes involved with first activating the item’s conceptual cluster, then selecting the proper word. Surprisingly, they discovered the two processes actually happen at the same time and activate a much wider network of brain regions than previously suspected. As expected, two regions known to be involved in language processing lit up, the left inferior frontal gyrus and the posterior temporal cortex. But so did several other regions not traditionally linked to language, including the medial and middle frontal gyri, the researchers reported in the Proceedings of the National Academy of Sciences.

“This work shows the word retrieval process in the brain is not at all as localized as we previously thought,” Ries said. “It’s not a clear division of labor between brain regions. It’s a much more complex process.”

Learning exactly how the brain accomplishes these tasks could one day help speech-language pathologists devise strategies for treating disorders that prevent people from readily accessing their vocabulary.

“Word retrieval is usually effortless in most people, but it is routinely compromised in patients who suffer from anomia, or word retrieval difficulty,” Ries said. “Anomia is the most common complaint in patients with stroke-induced aphasia, but is also common in neurodegenerative diseases and normal aging. So it is critical to understand how this process works to understand how to help make it better.”


Story Source:

Materials provided by San Diego State UniversityNote: Content may be edited for style and length.


Journal Reference:

  1. Stephanie K. Riès, Rummit K. Dhillon, Alex Clarke, David King-Stephens, Kenneth D. Laxer, Peter B. Weber, Rachel A. Kuperman, Kurtis I. Auguste, Peter Brunner, Gerwin Schalk, Jack J. Lin, Josef Parvizi, Nathan E. Crone, Nina F. Dronkers, Robert T. Knight. Spatiotemporal dynamics of word retrieval in speech production revealed by cortical high-frequency band activityProceedings of the National Academy of Sciences, 2017; 114 (23): E4530 DOI: 10.1073/pnas.1620669114

 

Source: San Diego State University. “Mapping how words leap from brain to tongue: Neuroscientist explores the complex brain connections employed during word retrieval.” ScienceDaily. ScienceDaily, 19 June 2017. <www.sciencedaily.com/releases/2017/06/170619144827.htm>.

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Date:
June 19, 2017

Source:
University of California – San Diego

Summary:
Can the continental United States make a rapid, reliable and low-cost transition to an energy system that relies almost exclusively on wind, solar and hydroelectric power? While there is growing excitement for this vision, a new study describes a more complicated reality. Researchers argue that achieving net-zero carbon emissions requires the incorporation of a much broader suite of energy sources and approaches.

 

This map shows wind resources across the contiguous United States at 80 meters above ground level. The team’s research says that this resource is variable, so a broad portfolio of other technologies is needed to move to a zero-emissions energy future.
Credit: Map is provided courtesy of Christopher Clack and Vibrant Clean Energy LLC

 

 

Can the continental United States make a rapid, reliable and low-cost transition to an energy system that relies almost exclusively on wind, solar and hydroelectric power? While there is growing excitement for this vision, a new study in the Proceedings of the National Academy of Sciences(PNAS) by 21 of the nation’s leading energy experts, including David G. Victor and George R. Tynan from the University of California San Diego, describes a more complicated reality. These researchers argue that achieving net-zero carbon emissions requires the incorporation of a much broader suite of energy sources and approaches.

The paper published by PNAS the week of June 19, 2017, with Christopher Clack as first author, provides a rigorous analysis that corrects a 2015 research roadmap indicating that the continental United States could be reliably powered at low cost, in as little as 35 to 40 years, relying on just solar, wind, and hydroelectric power. The researchers write that the conclusions in the 2015 paper are not supported by adequate and realistic analysis and do not provide a reliable guide to whether and at what cost such a transition might be achieved.

“Wind, solar and hydroelectric power can, and will, be important parts of any moves to decarbonize our energy system and therefore combat climate change, but given today’s technical challenges and infrastructure realities, renewables won’t be the only solution,” said Victor, an energy expert at the UC San Diego School of Global Policy and Strategy. Victor and fellow co-author Tynan, who is associate dean of the UC San Diego Jacobs School of Engineering, are co-directors of the Deep Decarbonization Initiative at UC San Diego, which they launched to tackle the interrelated policy and technology challenges that must be addressed to get to zero global carbon emissions.

“We need a broad portfolio of clean energy technologies in order to achieve an affordable transition to a low-carbon-emission energy system,” said Tynan, a professor in the Department of Mechanical and Aerospace Engineering at the Jacobs School and a member of the UC San Diego Center for Energy Research.

The new work references a number of analyses, meta-analyses and assessments, including those performed by the Intergovernmental Panel on Climate Change, the National Oceanic and Atmospheric Administration, the National Renewable Energy Laboratory, and the International Energy Agency, that have concluded that deployment of a diverse portfolio of clean energy technologies makes a transition to a low-carbon-emission energy system both more feasible and less costly than other pathways.

“A policy prescription that overpromises on the benefits of relying on a narrower portfolio of technologies options could be counterproductive, seriously impeding the move to a cost effective decarbonized energy system,” the authors write in the PNAS paper.

This discussion is particularly timely because proposals for rapid shifts to all or nearly all renewables are gaining increased attention from policy makers, politicians and the general public.

“Getting to 80 percent reduction in carbon emission rates is going to be tough, and decarbonizing beyond 80 percent will be even more challenging. That’s why it’s important to be as rigorous as possible in laying out a pathway to this goal,” Tynan said.

“When we talk about reducing the amount of carbon in the atmosphere — decarbonization — there is an increased recognition that a diversity of approaches is not only smart, but necessary,” said Victor, who is also co-director of the Laboratory for International Law and Regulation at UC San Diego and co-chairs the Energy Security and Climate Initiative at the Brookings Institution.

This kind of broad energy portfolio is likely to include bioenergy, wind, solar, hydroelectric, nuclear energy and carbon capture, the authors say.

“We are focused on helping governments, communities, companies and societies cut emissions of warming gases given the very real technological, economic and political constraints that exist,” Tynan said. “It’s important for policy makers and the public to understand we still have significant progress to make before we are have a realistic chance of achieving the required emissions reductions reliably and cost effectively.”

For the PNAS study, the authors identify many technical challenges to moving toward an energy system built solely on wind, solar and hydroelectric power.

The authors also argue for deploying new technologies and innovation, such as cutting-edge energy storage and new control systems. With experience, they say, a much greater role for renewable energy may be feasible.

“Ultimately we’re talking about getting to zero — getting our global carbon emissions to levels that will combat climate change immediately. This is deep decarbonization in the real world, cutting global emissions at scale while still meeting the energy needs of a growing, global population,” said Victo


Story Source:

Materials provided by University of California – San Diego. Original written by Daniel Kane and Anthony King. Note: Content may be edited for style and length.


Journal Reference:

  1. Christopher T. M Clack, Staffan A. Qvist, Jay Apt, Morgan Bazilian, Adam R. Brandt, Ken Caldeira, Steven J. Davis, Victor Diakov, Mark A. Handschy, Paul D. H. Hines, Paulina Jaramillo, Daniel M. Kammen, Jane C. S. Long, M. Granger Morgan, Adam Reed, Varun Sivaram, James Sweeney, George R. Tynan, David G. Victor, John P. Weyant, and Jay F. Whitacre. Evaluation of a proposal for reliable low-cost grid power with 100% wind, water, and solarPNAS, 2017 DOI: 10.1073/pnas.1610381114

 

Source: University of California – San Diego. “Fighting global warming and climate change requires a broad energy portfolio.” ScienceDaily. ScienceDaily, 19 June 2017. <www.sciencedaily.com/releases/2017/06/170619152208.htm>.

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Scott Mellis, MD, PhD on Safari

 

Our very good friend and colleague, Dr. Scott Mellis, Vice President, Early Clinical Development and Experimental Sciences, Rare Diseases at Regeneron Pharmaceuticals, took an adventurous trip to Africa and came back with some extraordinary photos.

Cheetahs enjoying a family meal in the Serengeti. ©Scott Mellis, M.D., Ph.D.

 

Lion outside safari vehicle.  Ngoro Ngoro crater © Scott Mellis, M.D., Ph.D.

 

For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.

 

Joyce Hays, Founder and Editor in Chief of On Target

Jules Mitchel, Editor

 

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Serotonin – Mens Sana in Corpore Sano

Source: http://worldhappiness.report/ed/2017/

 

Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract (GI tract), blood platelets, and the central nervous system (CNS) of animals, including humans. It is popularly thought to be a contributor to feelings of well-being and 1) ___Approximately 90% of the human body’s total serotonin is located in the enterochromaffin cells in the GI tract, where it is used to regulate intestinal movements. The serotonin is secreted luminally and basolaterally which leads to increased serotonin uptake by circulating platelets and activation after stimulation, which gives increased stimulation of myenteric neurons and gastrointestinal motility. The remainder is synthesized in serotonergic 2) ___of the CNS, where it has various functions. These include the regulation of mood, appetite, and sleep. Serotonin also has some cognitive functions, including memory and learning. Modulation of serotonin at synapses is thought to be a major action of several classes of pharmacological antidepressants. Serotonin secreted from the enterochromaffin cells eventually finds its way out of tissues into the blood. There, it is actively taken up by blood platelets, which store it. When the platelets bind to a clot, they release serotonin, where it serves as a vasoconstrictor and helps to regulate hemostasis and blood 3) ___. Serotonin is also a growth factor for some types of cells, which may give it a role in wound healing. There are various serotonin receptors.

 

Serotonin is metabolized mainly to 5-HIAA, chiefly by the liver. Metabolism involves first oxidation by monoamine oxidase to the corresponding aldehyde. This is followed by oxidation by aldehyde dehydrogenase to 5-HIAA, the indole acetic acid derivative. The latter is then excreted by the 4) ___. In addition to animals, serotonin is found in fungi and 5) ___. Serotonin’s presence in insect venoms and plant spines serves to cause pain, which is a side-effect of serotonin injection. Serotonin is produced by pathogenic amoebae, and its effect on the gut, causes diarrhea. Its widespread presence in many seeds and fruits may serve to stimulate the digestive tract into expelling the seeds.

 

Serotonin syndrome (SS) is a group of symptoms that may occur following use of certain serotonergic medications or 6) ___. The degree of symptoms can range from mild to severe. Symptoms include high body temperature, agitation, increased reflexes, tremor, sweating, dilated pupils, and diarrhea. Body temperature can increase to greater than 41.1 oC (106.0 oF). Complications may include seizures and extensive muscle breakdown. Serotonin syndrome is typically caused by the use of two or more serotonergic medications or drugs. This may include selective serotonin reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI), monoamine oxidase inhibitor (MAOI), tricyclic antidepressants (TCAs), amphetamines, pethidine (meperidine), tramadol, dextromethorphan, buspirone, L-tryptophan, St. John’s wort, triptans, ecstasy, metoclopramide, ondansetron, or cocaine. It occurs in about 15% of SSRI overdoses. It is a predictable consequence of excess serotonin on the CNS or 7) ___ ___ ___. Onset of symptoms is typically within a day of the extra serotonin. Diagnosis is based on a person’s symptoms and history of medication use. Other conditions that can produce similar symptoms such as neuroleptic malignant syndrome, malignant hyperthermia, anticholinergic toxicity, heat stroke, and meningitis should be ruled out. No laboratory tests can confirm the diagnosis. Initial treatment consists of discontinuing medications which may be contributing. In those who are agitated benzodiazepines may be used. If this is not sufficient, a serotonin antagonist such as cyproheptadine may be used. In those with a high body temperatures active cooling measures may be needed. The number of cases of serotonin syndrome that occur each year is unclear. With appropriate treatment the risk of 8) ___ is less than one percent. The high-profile case of Libby Zion, who is thought to have died from serotonin syndrome, resulted in changes to graduate medical education in New York State and hospital procedures. The symptoms of serotonin syndrome are often described as a clinical triad of abnormalities.

 

Non-pharmacologic ways to raise serotonin levels in humans are: light therapy, meditation, psychotherapy, exercise and diet. Another important factor that could play a role in raising 9) ___ levels, is diet. According to some evidence, tryptophan, which increases brain serotonin in humans is an effective antidepressant in mild-to-moderate depression. Further, in healthy people with high trait irritability, it increases agreeableness, decreases quarrelsomeness and improves mood. Although purified tryptophan increases brain serotonin, foods containing tryptophan do not. This is because tryptophan is transported into the brain by a transport system that is active toward all the large neutral amino acids, and tryptophan is the least abundant amino acid in protein. After the ingestion of a meal containing protein, the rise in the plasma level of the other large neutral amino acids will prevent the rise in plasma tryptophan from increasing brain tryptophan. The idea, common in popular culture, that a high-protein food such as turkey will raise brain tryptophan and serotonin is, unfortunately, false. Another popular myth that is widespread on the Internet is that bananas improve mood because of their serotonin content. Although it is true that bananas contain serotonin, it does not cross the blood-brain barrier. Researchers have studied the tryptophan content of both wild chickpeas and the domesticated chickpeas that were bred from them in the Near East in Neolithic times. In the cultivated group, the tryptophan content was almost twice that of the wild seeds. Interestingly, the greater part of the increase was due to an increase in the free tryptophan content (i.e., not part of the protein). In cultivated 10) ___, almost two-thirds of the tryptophan was in the free form. Editor’s note: In our reading for this article so far, domesticated chickpeas appear to be the best dietary source contributing to healthy human serotonin levels. There may be other foods, but we have not come across them yet.

 

In an article in Nature Biotechnology, Morris and Sands argue that plant breeders should be focusing more on nutrition than on yield. They ask, “Could consumption of tryptophan-rich foods play a role in reducing the prevalence of depression and aggression in society?“ The constitution of the WHO states “Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity.“ This may sound like simple common sense, but it’s worth stating that positive mood within the normal range is an important predictor of health and longevity. Research confirms what might be intuitively expected, that positive emotions and agreeableness foster congenial relationships with others. This in turn will create the conditions for an increase in social support. Several studies found an association between measures related to serotonin and mood in the normal range. Lower platelet serotonin receptor function was associated with lower mood in one study, whereas better mood was associated with higher blood serotonin levels in another. Low serotonin may predispose healthy individuals to suboptimal physical as well as mental functioning. There is a strong possibility that the interaction between serotonin synthesis and mood may be 2-way, with serotonin influencing mood and mood influencing serotonin.

 

The first World Happiness Report was published in April 2012, in support of the UN High Level Meeting on happiness and well-being. Since then the world has come a long way. Increasingly, happiness is the proper measure of social progress and the goal of public policy. In June 2016 the OECD committed itself “to redefine the growth narrative to put people’s well-being at the center of governments’ efforts.“ In February 2017, the United Arab Emirates held a full-day World Happiness meeting, as part of the World Government Summit. Clearly, health, happiness and non-pharmacologic serotonin levels, are closely related. Sources: www.ncbi.nlm.nih.gov; WebMD.com; Wikipedia

 

World Happiness Report video

 

ANSWERS: 1) happiness; 2) neurons; 3) clotting; 4) kidneys; 5) plants; 6) drugs; 7) Central Nervous System; 8) death; 9) serotonin; 10) chickpeas

 

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Serotonin Research & Three Great Scientists’ Contributions

Vittorio Erspamer MD, Photo credit: Unknown; Public Domain, Wikipedia Commons

 

Dr. Vittorio Erspamer (1909-1999), the well-known discoverer of serotonin and octopamine, was an Italian pharmacologist and chemist, known for the identification, synthesis and pharmacological studies of more than sixty new chemical compounds, most notably serotonin and octopamine.

 

Erspamer was born in 1909 in the small village of Val di Non in Malosco, a municipality of Trentino in northern Italy. He attended school in the Roman Catholic Archdiocese of Trento and then moved to Pavia, where he studied at Ghislieri College, graduating in medicine and surgery in 1935. He then took the post of assistant professor in anatomy and physiology at the University of Pavia – one of the oldest universities in Europe, founded in 1361. In 1936, he obtained a scholarship to study at the Institute of Pharmacology at the University of Berlin. After returning to Italy in 1939, he moved to Rome where he took up the position of professor in pharmacology. In Rome, the focus of his research shifted to drugs and he used his past biological experience to focus on compounds isolated from animal tissues. In 1947 he became professor of pharmacology at the Faculty of Medicine at the University of Bari. In 1955, he moved from Bari to Parma, to assume an equivalent position of professor of pharmacology at the Faculty of Medicine, University of Parma. Erspamer was one of the first Italian pharmacologists to realize that fruitful scientific research benefits from building a relationship with the chemical and pharmaceutical industries. In the late 1950s, he established a collaboration with chemists at the Farmitalia company. The collaboration was useful, not only for the analysis of the structure of new molecules which he isolated and characterized pharmacologically, but also for the subsequent industrial synthesis of these chemicals and their synthetic analogs.

 

Thanks to funding received from Farmitalia, over the years Erspamer collected more than five hundred species of marine organisms from all around the world, including amphibians, shellfish, sea anemones and other species. For this purpose, he spent much time in traveling, and was known among his colleagues for his careful preparation of expeditions and knowledge of geography. Using these world-wide observations he developed a theory of geo-phylogenetic correlations among the different amphibian species of the world, which was based on analysis of the peptides and amines in their skin.

 

The research activities of Erspamer spanned more than 60 years and resulted in the isolation, identification, synthesis and pharmacological study of more than sixty new chemical compounds, especially polypeptides and biogenic amines, but also some alkaloids. Most of these compounds were isolated from animals, predominantly amphibians. In the late fifties his research shifted to peptides. In the laboratories of the Institute of Medical Pharmacology, University of Rome, he isolated from amphibians and mollusks more than fifty new bioactive peptides. These became the subjects of numerous studies in other laboratories in Europe and North America. In 1979, he focused on opioid peptides specific to Phyllomedusa, a genus of tree frog from Central and South America. These were used by the native Indians in initiation rites, to increase their prowess as “hunters” and make them feel “invincible”. They applied secretions from the skin of these frogs that resulted in euphoric and analgesic effects. The peptides studied by Erspamer have become essential to characterize the functional role of opioid receptors.

 

Erspamer retired from administrative positions in 1984 because of the age limits, but continued his research and writing until his death in Rome in 1999. His last, unfinished review was completed by his collaborators and published in 2002. During his lifetime he was twice nominated for the Nobel Prize.

 

Between 1933 and 1934, while still a college student, Erspamer published his first work on the histochemical characteristics of enterochromaffin cells using advanced techniques, not normally used at that time, such as diazo reactions, Wood’s lamp and fluorescence microscopy. In 1935, he showed that an extract prepared from enterochromaffin cells made intestinal tissue contract. Other chemists believed the extract contained adrenaline, but two years later Erspamer demonstrated that it was a previously unknown chemical, an amine, which he named enteramine and which was renamed, later as serotonin. In 1948, Maurice M. Rapport, Arda Green, and Irvine Page of the Cleveland Clinic discovered a vasoconstrictor substance in blood serum, and since it was a serum agent affecting vascular tone, they named it serotonin. In 1952 it was shown that enteramine was the same substance as serotonin. Another important chemical, also an amine, was discovered by Erspamer in 1948, in the salivary glands of the octopus, and therefore named by him octopamine.

 

Maurice Rapport (1919-2011) was a biochemist who is best known for his work with the neurotransmitter serotonin. Rapport, Irvine H. Page, and Arda A. Green worked together to isolate and name the chemical. Alone, Rapport identified its structure and published his findings in 1948. Research since its discovery has implicated serotonin with mood regulation, appetite, reproductive drives, and sleep as well as gastrointestinal roles. After his work with serotonin, Rapport did important research with cancer, cardiovascular disease, connective-tissue disease and demyelinating diseases.

 

Maurice Rapoport was born on September 23, 1919 in Atlantic City, New Jersey. His mother changed the spelling of the family name to Rapport. His father was a furrier from Russia who left the family when Rapport was a small child. Rapport graduated from DeWitt Clinton High School in the Bronx, New York and went on to earn a bachelor’s degree in chemistry from the City College of New York in 1940. He obtained his doctorate in organic chemistry in 1946 from California Institute of Technology. In 1946, Maurice Rapport began working in the Cleveland Clinic Foundation which was directed by Irvine H. Page. Since the 1860s, a substance was known about, in the serum of blood vessels, that promoted clotting. Rapport was assigned the project of isolating this serum. They enlisted the help of Arda A. Green, a physical biochemist. The substance was acquired by leaving a test tube of the reagents in a cold room while Rapport went on vacation. When he returned he isolated the crystals of the desired substance. In a paper published in 1948, they gave it a name: serotonin, derived from “serum“ and “tonic“.

 

In 1948, Rapport left the Cleveland Clinic for a position at Columbia University and continued searching for serotonin’s structure. In May 1949, the structure of serotonin was discovered to be 5-hydroxytryptamine (5-HT). Serotonin was found to be the same substance that Dr. Vittorio Erspamer had been studying since the 1930s called “enteramine“. Enteramine had a substantial place in scientific literature due to Erspamer’s research into its role in smooth muscle constriction and intestinal tracts. Erspamer’s research contributed to Rapport’s discovery of serotonin’s structure and allowed other researchers to synthesize the substance and further study its role in the body.

 

The structure of serotonin was given to Upjohn Drug Company where researchers focused on the role of serotonin in the bodily processes such as blood vessel constriction. In 1954, Betty Twarog discovered the distribution of serotonin in the brain. Further research illustrated how serotonin plays a major role in the central nervous system and digestive tract. The understanding of serotonin has led to a progression in our view of mental illness and allowed the development of antidepressants and other drugs for hypertension and migraines. After his work with serotonin, Rapport worked at the Sloan-Kettering Institute for Cancer Research. His contributions involved the activity and structures of lipids in relation to immunological activity. Specifically, he isolated cytolipin H from human cancer tissue in 1958. This led to a better understanding of our immune system. He also was a professor at the Albert Einstein College of Medicine. There he isolated two glysosphingolipids and studied antibodies to gangliosides. These findings were useful to further pharmacological studies relating these substances to demyelinating diseases such as Amyotrophic Lateral Sclerosis (ALS).

In 1968, Rapport returned to Columbia University as chief of pharmacology and professor of biochemistry. The next year, he became the chief of the new neuroscience division which combined the chemistry, pharmacology, and bacteriology divisions. He retired in 1986 and remained in the neurology department of the Albert Einstein College of Medicine as a visiting professor.

 

Betty Mack Twarog (1927 – 2013) was an American biochemist who was the first to find serotonin in the mammalian brain.. She attended Swarthmore College from 1944 to 1948, focusing on mathematics. While studying for an M.Sc. at Tufts College she heard a lecture on mollusc muscle neurology and in 1949 enrolled under John Welsh in the PhD program at Harvard to study this area. By 1952 she had submitted a paper showing that serotonin had a role as a neurotransmitter in mussels. In Autumn 1952 Twarog moved for family reasons to the Kent State University area , and chose the Cleveland Clinic as a place to continue her study of her hypothesis that invertebrate neurotransmitters would also be found in mammals. Although her supporter there, Irvine Page did not believe serotonin would be found in the brain, he nevertheless gave Twarog a laboratory and technician. By June 1953 a paper was submitted announcing the isolation of serotonin in mammalian brain. Twarog left the Cleveland Clinic in 1954 and continued to work on invertebrate smooth muscle at Tufts, Harvard and SUNY at Stony Brook. In later years, at the Bigelow Laboratory for Ocean Sciences in Boothbay Harbor, Maine she worked on how shellfish evade phytoplankton poisons. Twarog died on February 6, 2013, at the age of 85 in Damariscotta, Maine.

 

Twarog’s isolation of serotonin in brain established its potential as a neurotransmitter and thus a modulator of brain action. Her discovery was an essential precursor to the creation in 1978 of the antidepressant SSRI medicines such as fluoxetine and sertraline.

 

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Repurposed Experimental Cancer Therapy Treats Muscular Dystrophy

 

Duchenne muscular dystrophy (DMD) is a degenerative muscle disease that usually begins in childhood and has no known cure. It is caused by a faulty gene that leads to progressive muscle weakness, with death often occurring around age 25. Those with DMD lack dystrophin, a protein akin to a molecular shock-absorber that helps keep muscle cells intact. Without dystrophin, muscles are fragile and easily injured. Individuals lose muscle strength and the ability to repair damaged muscle tissue. Most die from heart or respiratory problems.

 

According to an article published in Molecular Therapy (June 2017), researchers at the National Institutes of Health’s National Center for Advancing Translational Sciences (NCATS) and the University of Nevada, Reno School of Medicine (UNR Med) have demonstrated that a drug originally targeted unsuccessfully to treat cancer may have new life as a potential treatment for DMD. The candidate drug, SU9516, represents a different kind of approach for treating DMD. Rather than trying to fix or replace the broken gene, SU9516 ramps up the muscle repair process, helping reinforce muscle structure. To accomplish this, the research team screened more than 350,000 compounds to find SU9516, which had been previously developed as a treatment for leukemia. The research demonstrated that this compound improved muscle function in both laboratory and animal DMD models.

 

In earlier research, the senior author of the current study showed that boosting the levels of a cell structural protein, a7beta1 integrin, in affected muscle cells could alleviate DMD symptoms in a mouse model. In addition, increased amounts of the protein slowed the disease’s progress. The screening exercise searched for compounds for molecules that could increase a7beta1 integrin production in mouse muscle cells grown in the laboratory. The screen revealed that SU9516 raised integrin production and promoted the formation of muscle cells and fibers from DMD muscle stem cells, another important indication of its potential as a drug. In a series of pre-clinical experiments, the authors showed that SU9516 increased the production of a7?1 integrin in human and mouse DMD muscle cells. Subsequent tests found SU9516 improved muscle function and slowed indicators of disease progression. The authors suggests that such a drug could be used alone, or in combination, with other therapies yet to be developed, and that there might also be a wide ranging applications to other muscle-damaging conditions, like cachexia, a wasting syndrome characterized by weight loss and muscle atrophy that is often seen in the late stages of cancers, and the effects of aging and injury.

 

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Drinking Diet Beverages During Pregnancy Linked to Child Obesity

 

Childhood obesity is known to increase the risk for certain health problems later in life, such as diabetes, heart disease, stroke and some cancers.

 

According to an article published online in the International Journal of Epidemiology (6 June 2017), it was reported that children born to women who had gestational diabetes and drank at least one artificially sweetened beverage per day during pregnancy, were more likely to be overweight or obese at age 7, compared to children born to women who had gestational diabetes and drank water instead. The study showed that as the volume of amniotic fluid increases, pregnant women tend to increase their consumption of fluids. To avoid extra calories, many pregnant women replace sugar-sweetened soft drinks and juices with beverages containing artificial sweeteners. Citing prior research implicating artificially sweetened beverages in weight gain, the study authors sought to determine if diet beverage consumption during pregnancy could influence the weight of children.

 

The study analyzed data collected from 1996 to 2002 by the Danish National Birth Cohort, a long-term study of pregnancies among more than 91,000 women in Denmark. At the 25th week of pregnancy, the women completed a detailed questionnaire on the foods they ate. The study also collected data on the children’s weight at birth and at 7 years old. For the current analysis, the authors limited their analysis to data from more than 900 pregnancies that were complicated by gestational diabetes, a type of diabetes that occurs only during pregnancy. Results showed that approximately 9% of these women reported consuming at least one artificially sweetened beverage each day. Their children were 60% more likely to have a high birth weight, compared to children born to women who never drank sweetened beverages. At age 7, children born to mothers who drank an artificially sweetened beverage daily were nearly twice as likely to be overweight or obese. Consuming a daily artificially sweetened beverage also appeared to offer no advantages over consuming a daily sugar-sweetened beverage. At age 7, children born to both groups were equally likely to be overweight or obese. However, women who substituted water for sweetened beverages reduced their children’s obesity risk at age 7 by 17%.

 

It is not well understood why drinking artificially sweetened beverages compared to drinking water may increase obesity risk. The authors cited an animal study that associated weight gain with changes in the types of bacteria and other microbes in the digestive tract. Another animal study suggested that artificial sweeteners may increase the ability of the intestines to absorb the blood sugar glucose. Other researchers found evidence in rodents that, by stimulating taste receptors, artificial sweeteners desensitized the animals’ digestive tracts, so that they felt less full after they ate and were more likely to overeat. The authors caution that more research is necessary to confirm and expand on their current findings, and that although they could account for many other factors that might influence children’s weight gain, such as breastfeeding, diet and physical activity levels, their study couldn’t definitively prove that maternal artificially sweetened beverage consumption caused the children to gain weight. The authors mention specifically the need for studies that use more contemporary data, given recent upward trends in the consumption of artificially sweetened beverages. They also call for additional investigation on the effects of drinking artificially sweetened beverages among high-risk racial/ethnic groups.

 

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Fostering Medical Innovation: A Plan for Digital Health Devices

 

The following was reported by Scott Gottlieb, M.D., FDA Commissioner

 

Dr. Gottlieb indicated that it is incumbent upon FDA to ensure that they have the right policies in place to promote and encourage safe and effective innovation that can benefit consumers, and adopt regulatory approaches to enable the efficient development of these technologies. By taking an efficient, risk-based approach to regulations, FDA can promote health through the creation of more new and beneficial medical technologies. FDA can also help reduce the development costs for these innovations by making sure that our own policies and tools are modern and efficient, giving entrepreneurs more opportunities to develop products that can benefit people’s lives.

 

To this end, FDA will soon be putting forward a broad initiative that is focused on fostering new innovation across our medical product centers. However, today Dr. Gottlieb is focusing on one critical aspect of this innovation initiative: A new Digital Health Innovation Plan that is focused on fostering innovation at the intersection of medicine and digital health technology. This plan will include a novel, post-market approach to how FDA intends to regulate these digital medical devices.

 

According to one estimate, last year there were 165,000 health-related apps available for smartphones. Forecasts predict that such apps would be downloaded 1.7 billion times by 2017. From mobile apps and fitness trackers to clinical decision support software, innovative digital technologies have the power to transform health care in important ways, such as:

 

1. Empowering consumers to make more and better decisions every day about their own health, monitor and manage chronic health conditions, or connect with medical professionals, using consumer-directed apps and other technologies to help people live healthier lifestyles through fitness, nutrition, and wellness monitoring;

2. Enabling better and more efficient clinical practice and decision making through decision support software and technologies to assist in making diagnoses and developing treatment options; managing, storing, and sharing health records; and managing schedules and workflow;

3. Helping to address public health crises, such as the opioid epidemic that is devastating many American communities. In fact, FDA conducted a prize competition to encourage the development of a mobile app to help connect opioid users experiencing an overdose with nearby carriers of the prescription drug naloxone for emergency treatment.

 

For these and other digital technologies to take hold and reach their fullest potential, it is critical that FDA be forward-leaning in making sure that they have implemented the right policies and regulatory tools, and communicated them clearly.In this rapidly changing environment, ambiguity regarding how FDA will approach a new technology can lead innovators to invest their time and resources in other ventures. To encourage innovation, FDA should carry out its mission to protect and promote the public health through policies that are clear enough for developers to apply them on their own. Developers should not have to seek out, on a case-by-case basis, FDA’s position on every individual technological change or iterative software development.

 

Congress has already taken a major step to advance these goals in the 21st Century Cures Act. Expanding upon policies advanced by FDA’s Center for Devices and Radiological Health (CDRH), the Act revised FDA’s governing statute to, among other things, make clear that certain digital health technologies – such as clinical administrative support software and mobile apps that are intended only for maintaining or encouraging a healthy lifestyle – generally fall outside the scope of FDA regulation. Such technologies tend to pose low risk to patients but can provide great value to the health care system. FDA, led by CDRH, is working to implement the digital health provisions of the 21st Century Cures Act and, in the coming months, will be publishing guidance to further clarify what falls outside the scope of FDA regulation and to explain how the new statutory provisions affect pre-existing FDA policies. FDA will provide guidance to clarify their position on products that contain multiple software functions, where some fall outside the scope of FDA regulation, but others do not. In addition, FDA will provide new guidance on other technologies that, although not addressed in the 21st Century Cures Act, present low enough risks that FDA does not intend to subject them to certain pre-market regulatory requirements. Greater certainty regarding what types of digital health technology is subject to regulation and regarding FDA’s compliance policies will not only help foster innovation, but also will help the agency to devote more resources to higher risk priorities.

 

In addition to these efforts, FDA has announced a new initiative. This fall, as part of a comprehensive approach to the regulation of digital health tools and in collaboration with our customers, FDA will pilot an entirely new approach toward regulating this technology. This will be the cornerstone to a more efficient, risk-based regulatory framework for overseeing these medical technologies. While the pilot program is still being developed, FDA is considering whether and how, under current authorities, they can create a third party certification program. Under this program, lower risk digital health products could be marketed without FDA premarket review and higher risk products could be marketed with a streamlined FDA premarket review. Certification could be used to assess, for example, whether a company consistently and reliably engages in high quality software design and testing (validation) and ongoing maintenance of its software products. Employing a unique pre-certification program for software as a medical device (SaMD) could reduce the time and cost of market entry for digital health technologies.

 

In addition, post-market collection of real-world data might be able to be used to support new and evolving product functions. For example, product developers could leverage real-world data gathered through the National Evaluation System for health Technology (NEST) to expedite market entry and subsequent expansion of indications more efficiently. NEST will be a federated virtual system for evidence generation composed of strategic alliances among data sources including registries, electronic health records, payer claims, and other sources. The Medical Device Innovation Consortium (MDIC), a 501(c)(3) public-private partnership, is serving as an independent coordinating center that operates NEST. In the coming weeks, MDIC will announce the establishment of a Governing Committee for the NEST Coordinating Center comprised of stakeholder representatives of the ecosystem, such as patients, health care professionals, health care organizations, payers, industry, and government. Although FDA does not own or operate NEST, they have been establishing strategic alliances among data sources to accelerate NEST’s launch with the initial version of a fully operational system anticipated by the end of 2019. Applying this firm-based approach, rather than the traditional product-based approach, combined with leveraging real-world evidence, would create market incentives for greater investment in and growth of the digital health technology industry. Such processes could enable developers to deploy new or updated software more rapidly and would help FDA to better focus its resources.

 

Through these and other steps, according to Dr. Gottlieb, FDA will help innovators navigate a new, modern regulatory process so that promising, safe and effective developments in digital health can advance more quickly and responsibly, and Americans can reap the full benefits from these innovations. These efforts are just one part of a much broader initiative that FDA is currently undertaking to advance policies that promote the development of safe and effective medical technologies that can help consumers improve their health. FDA’s goal is to make sure that FDA has the most modern and efficient regulatory approaches when it comes to evaluating new, beneficial technologies. Scott Gottlieb, M.D., is Commissioner of the U.S. Food and Drug Administration

 

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