Study could lead to novel therapeutics aimed at reducing pathological fear in PTSD

May 15, 2017

University of California – Riverside

Research on ‘fear memory’ could lead to the development of therapies that reduce the effects of PTSD, which affects 7 percent of the US population. The researchers found that a population of hippocampal neurons project to both the amygdala and the medial prefrontal cortex, and that these neurons efficiently convey information to the two brain areas to encode and retrieve fear memory for a context associated with an aversive event.


Research published by scientists at the University of California, Riverside on “fear memory” could lead to the development of therapies that reduce the effects of post-traumatic stress disorder (PTSD).

To survive in a dynamic environment, animals develop adaptive fear responses to dangerous situations, requiring coordinated neural activity in the hippocampus, medial prefrontal cortex (mPFC), and amygdala — three brain areas connected to one another. A disruption of this process leads to maladaptive generalized fear in PTSD, which affects 7 percent of the U.S. population.

Jun-Hyeong Cho, an assistant professor of cell biology and neuroscience and Woong Bin Kim, a postdoctoral researcher in Cho’s lab, have now found that a population of hippocampal neurons project to both the amygdala and the mPFC, and that it is these neurons that efficiently convey information to these two brain areas to encode and retrieve fear memory for a context associated with an aversive event.

The study, which appeared in the May 10 print issue of the Journal of Neuroscience, is the first to quantify these “double-projecting” hippocampal neurons and explain how they convey contextual information more efficiently for fear responses, compared to hippocampal neurons that project only to either the mPFC or the amygdala.

“This study, done using a mouse model, expands our understanding of how associative fear memory for a relevant context is encoded in the brain,” said Cho, the lead author of the study and a member of the UCR School of Medicine’s Center for Glial-Neuronal Interactions, “and could inform the development of novel therapeutics to reduce pathological fear in PTSD.”

To visualize the double-projecting hippocampal neurons, Cho and Kim used a tracing method in which hippocampal neurons that project to different brain areas were labeled with fluorescence proteins with different colors. The pair also developed a novel approach of electrophysiological recordings and optogenetics to examine how exactly the double-projecting neurons connected to the mPFC and amygdala. (These experimental approaches can be used to examine other brain areas that project to multiple targets.)

“We were surprised to find that as much as 17 percent of hippocampal neurons that projected to the amygdala or the mPFC were, in fact, double-projecting neurons,” Cho said. “Although previous studies demonstrated the existence of double-projecting hippocampal neurons, neuroscientists largely ignored them when studying the role of neural pathways between the hippocampus, amygdala and mPFC in contextual fear learning.”

Cho explained that the acquisition (encoding) and retrieval of contextual fear memory requires coordinated neural activity in the hippocampus, amygdala and mPFC. The hippocampus encodes context cues, the amygdala stores associations between a context and an aversive event, and the mPFC signals whether a defensive response is appropriate in the present context.

Context is broadly defined as the set of circumstances around an event. In contextual fear conditioning, experimental subjects are placed in an emotionally neutral context (such as a room) and presented an aversive stimulus (such as an electrical shock). Then, they learn to associate the context with the aversive event, and show fear responses (such as freezing behavior) when placed subsequently in that context.

“Our study suggests that double-projecting hippocampal neurons can facilitate synchronized neural activity in the mPFC and amygdala that is implicated in learned fear,” he said. “It is by modulating the activity of the mPFC and basal amygdala that these double-projecting hippocampal neurons contribute to the acquisition and retrieval of fear memory for a context associated with an aversive event.”

Cho also explained that multiple projections from single neurons appear to be a general feature of the neural circuits in the brain and could promote synchronized neural activity and long-term changes in the efficiency of neural communication.

The study came about when, a few years ago, Cho and Kim were selectively labeling and stimulating hippocampal neurons that project to the mPFC, and examining how this manipulation affects fear memory formation in mice. When they carefully examined the brain tissue, they found that labeled hippocampal neurons also projected to the amygdala.

“We initially thought there was something wrong with our experiments,” Kim, the postdoctoral researcher, said. “But, when we repeated the experiments, the same pattern was observed consistently. We realized that this could be an exciting finding that may account for how contextual information is processed and conveyed between brain areas for the formation of fear memory for the context associated with an aversive event.”

Next, to better understand the role of double-projecting hippocampal neurons in fear learning and memory, Cho and Kim plan to selectively silence these neurons and examine how this manipulation impacts the formation of fear memory for a context associated with an aversive event.

Story Source:

Materials provided by University of California – Riverside. Original written by Iqbal Pittalwala. Note: Content may be edited for style and length.

Journal Reference:

  1. Woong Bin Kim, Jun-Hyeong Cho. Synaptic Targeting of Double-Projecting Ventral CA1 Hippocampal Neurons to the Medial Prefrontal Cortex and Basal Amygdala. The Journal of Neuroscience, 2017; 37 (19): 4868 DOI: 10.1523/JNEUROSCI.3579-16.2017


Source: University of California – Riverside. “Study expands understanding of how the brain encodes fear memory: Study could lead to novel therapeutics aimed at reducing pathological fear in PTSD.” ScienceDaily. ScienceDaily, 15 May 2017. <>.

Webinar (May 18, 2017): Making Registries Into Reusable Platforms for Conducting Clinical Trials


The Clinical Trials Transformation Initiative (CTTI) is hosting a special webinar in which it will unveil new recommendations for registry assessment and design that can assist in making embedded clinical trials suitable for regulatory purposes. The presenters of the webinar will be:


John Laschinger, MD, Medical Officer, Center for Devices and Radiological Health, U.S. FDA, and

Jules Mitchel, MBA, PhD, President, Target Health Inc.


Here are the details:


Title: CTTI Recommendations from the Registry Trials Project
Date: May 18, 2017 12:00-1:00 p.m. ET (GMT-05:00)
Webinar Link: When it’s time, Join the Meeting

The webinar will include the following practical, evidence-based strategies:


How to assess the reliability, relevance, and robustness of registry data

How to assure patient protections

How to make modifications needed to accommodate research needs


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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Medical Research Using Plants as Scaffolds for Human Tissue & Organs

Parsley Plant; Credit: Jonathunder – Own work, GFDL 1.2,


Researchers at the University of Washington-Madison were able to grow skin, brain, bone marrow and blood 1) ___ on plants using a highly-specialized, natural scaffolding from plants like parsley. The researchers collaborated with the Olbrich Botanical Gardens to identify plant species that show scaffolding potential, which in turn could be turned into structures for biomedical purposes. The researchers observed that certain plant species possess strength, rigidity and porosity as well as low mass and surface area, and that these characteristics make for a structurally-efficient 2) ___. The researchers also noted that plants have really high surface area to volume ratio, while their porous structure facilitates fluid transport, and that 3D printed stem cell scaffold helped support, feed and organize the cells. John Wirth, Olbrich’s conservatory curator, said the idea was a good way to use the living plant material to develop 3) ___ tissue. Parsley, orchid, and vanilla were among the plant species chosen for the study. Bamboo, wasabi, and elephant ear plant were also among the plants where cellulose was derived since plants have a huge capacity to grow 4) ___ populations According Bill Murphy, co-director of the UW-Madison Stem Cell and Regenerative Medicine Center, plants can deliver fluids very efficiently to their leaves and at the microscale, they’re very well organized. Murphy added that the vast diversity in the plant kingdom provides virtually any size and shape of interest, and that plants are extraordinarily good at cultivating new tissues and 5) ___. Plants, therefore, represent a tremendous feedstock of new materials for tissue engineering applications.


Study details: Cellulose and 3D scaffolding techniques


The researchers decellularized the plant materials leaving only cellulose, the basic components of a plant’s cell walls. The team then added peptides to serve as biological fasteners since human cells have no affinity to cellulose. Advanced technologies such as 3D printing and injection molding were used to create the three-dimensional scaffolds. It was found that eliminating all the other cells that make up the plant and retaining only the 6) ___ husks encouraged human stem cells such as fibroblasts to attach to the scaffold and develop miniature structures. Fibroblasts are common connective tissue cells that result from stem cell cultivation. Stem cells seeded into the scaffold also appeared to align themselves along its structure. This mechanism indicates a potential to use the materials in order to regulate the structure and alignment of developing human tissues, which may prove crucial for nerve and muscle tissues that need alignment and patterning. The plant scaffolds proved to be pliable, inexpensive, renewable and can be easily mass-7) ___, Murphy said. The researchers plan to conduct the efficacy of plant scaffolds in animal studies. While plant toxicity is highly unlikely, it could trigger immune responses when the plant scaffolds were implanted to mammals. However, significant immune response may not be apparent in their prospective study as plant cells were already taken out of the scaffolds. According to the researchers, the results suggest that plants may serve as an alternative to artificial scaffolds used in growing stem cells. Growing clusters of human stem cells that mimic organs in the laboratory may also be used on tissue implants in the near future. The findings were published in the journal Advanced Healthcare Materials.


Short History of Parsley


Apiole is a phenylpropene, also known as apiol, parsley apiol or parsley camphor. Its chemical name is 1-allyl-2,5-dimethoxy-3,4-methylenedioxybenzene. It is found in the essential oils of celery leaf and all parts of 8) ____. Heinrich Christoph Link, an apothecary in Leipzig, discovered the substance in 1715 as greenish crystals reduced by steam from oil of parsley. In 1855 Joret and Homolle discovered that apiol was an effective treatment of amenorrea or lack of menstruation. Parsley has been used In medicine as essential oil or in purified form, for the treatment of menstrual disorders and as an abortifacient. It is an irritant and, in high doses, it can cause liver and kidney 9) ___. Cases of death due to attempted abortion using apiol have been reported. Hippocrates wrote about parsley as a herb to cause an abortion. Plants containing apiole were used by women in the Middle Ages to terminate pregnancies. Now that safer methods of 10) ___ are available, apiol is almost forgotten.


Apiole (always with the final ‘e’) is the correct spelling of the trivial name for 1-allyl-2,5-dimethoxy-3,4-methylenedioxybenzene. Apiol, also known as ‘liquid apiol’ or ‘green oil of parsley’ is the extracted oleoresin of parsley, rather than the distilled oil. Its use was widespread in the USA, often as ergoapiol or apergol, until a highly toxic adulterated product containing apiol and tri-ortho-cresyl phosphate (also famous as the adulterant added to Jamaican ginger) was introduced on the American market. 1′-sulfoxy metabolite formation for apiole (3,4-OMe-safrole) is about 1/3 as active as safrole. No carcinogenicity was detected with parsley apiol or dill apiol in mice.


ANSWERS: 1) vessels; 2) scaffold; 3) human; 4) cell; 5) organs; 6) cellulose; 7) produced; 8) parsley; 9) damaged; 10) abortion


Jan Evangelista Purkyne, Medical Researcher, Cell Biologist (1787-1869)

1856: Jan Evangelista Purkyne


Jan Evangelista Purkyne (Czech: also written Johann Evangelist Purkinje) (1787-1869) was a Czech anatomist and physiologist. He was one of the best known scientists of his time. In 1839, he coined the term ?protoplasm’ for the fluid substance of a cell. His son was the painter Karel Purkyne. Such was his fame that when people from outside Europe wrote letters to him, all that they needed to put as the address was “Purkyne, Europe”. He is buried in the Czech National Cemetery in Vysehrad, Prague, modern-day Czech Republic.


Jan Evangelista Purkyne was born on December 17, 1787, in Libochovice, in what was then the Czech territory in the Austro-Hungarian monarchy. His father was an estate manager. After his father’s death when Jan was 6, he was encouraged to become a priest. These plans along with his own poverty led to a situation in which, from the age of 10, he was driven from one Piarist monastery school to another, learning German and Latin along the way. He was sent to the Piarist Philosophical Institute in Litomysl, and later, the Philosophical Institute in Prague. As a recent graduate of Prague’s Institute, he earned money as a tutor of rich children. In 1813, he took up medical studies at the University of Prague and in 1818, he graduated from the medical faculty. He then obtained a doctorate in 1819, following a thesis on subjective visual phenomena. By way of self-examination, he established that the visual sensations are caused by brain activity and the brain’s connection to the eye, such that they might not be triggered by external stimulation. Purkyne became a prosector, a  person with the special task of preparing a dissection for demonstration, and an assistant in the Physiology Institute at the University of Prague, but he had no opportunities to carry out his own experiments. He conducted research on vertigo phenomena, still relying on the method of self-examination in a Prague fairground on a carousel. He noticed that the vertigo direction is independent of the direction of rotation, but depends instead on the position of the head in relation to the body. Additionally, he described the phenomena of nystagmus, a vision condition in which the eyes make repetitive, uncontrolled movements, resulting in reduced vision and depth perception and can affect balance and coordination. Purkyne also analyzed the physiological phenomena that occurred after the use of certain drugs, including camphor, opium, digitalis and belladonna. He experimented on himself, sometimes going to dangerous extremes. He noticed that using one drug after another seemed to intensify the effect of the first one. He observed, nearly 30 years before Helmholtz, the interior of the eye in the light reflected into it by concave lenses. He noticed some differences of color detection in dim light, especially in comparison with the detection in daylight – what was then called the “Purkyne phenomenon“. Nowadays, it is explained by differential rod and cone excitation. He also emphasized the significance of fingerprints in crime detection, an idea that was an absolute innovation at that time.


Purkyne applied for a teaching position at many universities in the Austrian Empire. However, he was unsuccessful on many occasions. He was a Czech, and university officials preferred to promote German citizens to academic positions. Fortunately, his doctorate thesis was well received, and caught the attention of Goethe, who was interested in the same issue. With strong support shown by Goethe and Aleksander von Humboldt, in 1823, he was offered the position of the Professor of Physiology at the University of Breslau. His candidacy was accepted despite strong opposition from the faculty members. Thus, the most fruitful period of his career began. Purkyne’s successes in Breslau were based on excellent equipment and new techniques for the preparation of research material. He had a very modern and accurate microscope and microtome. He was the first to establish that the whole body is composed of cells. He did this 2 years ahead of T. Schwann. Paradoxically, in the history of science, Schwann is more commonly connected with this discovery. This may have resulted from the fact that Purkyne’s main interest was the inside of the cell, while Schwann described the cell membrane and was the first to use the word “cell“. Undoubtedly, Purkyne was the first to observe and account for the cell nucleus. He also noticed that cells are the structural components of animals and plants. He introduced the terms “protoplasm“ of the cells, and “plasma“ of the blood into the scientific language.


The modern techniques of Purkyne’s time allowed him to obtain his neurological results. In 1837, he published a paper about the ganglion cells in the brain, spinal cord, and cerebellum. He was the first to notice the significance of the grey substance of the brain. Before his discovery, scientists thought that only the white substance and nerves had any meaning. He emphasized that those cells are the centers of neurological function and that nerve fibers are like wires that transmit power from the nerves to the whole body. He accurately described the cells in the middle layer of the cerebellum with dendrites branching like a tree. They were then called Purkyne cells. Purkyne’s discoveries were often published in the dissertations of his assistants. He supervised the doctorate of David Rosenthal (1821-1875); they jointly discovered that nerves have fibers inside, and analyzed the number of nerve fibers in spinal and cranial nerves. Purkyne also established that sleep is caused by a decrease of external impulses. He conducted research on the effects of partial destruction of the animal brain by needles, being one of the earliest researchers to use this method. For many years, Purkyne used a special rotating chair and recorded all the optical, motion-associated, and physiological signs accompanying vertigo. He carried out studies in which he directed the galvanic current flow through his own skull, and observed the resulting vertigo and physiological phenomena. He determined the movement of cilia in the genital and respiratory systems, and ultimately, in the ventricles of the brain as well. In 1839, Purkyne discovered the fibrous tissue that transmits electrical impulses from the atrioventricular node to the ventricles of the heart. Today, they are called the Purkyne fibers.


In 1839, Purkyne opened the Physiological Institute in Wroclaw, which was the first such institute in the world. He became the dean of the medical faculty, elected to this position four times in a row. In 1850, he became a professor of physiology at the University of Prague. There, he concentrated on encouraging a return to the use of the Czech language instead of German in the university’s operations. He discovered the Purkinje effect, the human eye’s much reduced sensitivity. to dim red light compared to dim blue light. He published two volumes, Observations and Experiments Investigating the Physiology of Senses and New Subjective Reports about Vision, which contributed to the emergence of the science of experimental psychology. He created the world’s first Department of Physiology at the University of Breslau in Prussia (now Wroclaw, Poland) in 1839 and the world’s first official physiology laboratory in 1842. Here he was a founder of the Literary-Slav Society.


Personal Sigil 1837


Purkinje effect: simulated appearance of a red geranium and foliage in normal bright-light (photopic) vision, dusk (mesopic) vision, and night (scotopic) vision


Purkinje is best known for his 1837 discovery of Purkinje cells, large neurons with many branching dendrites found in the cerebellum. He is also known for his discovery in 1839 of Purkinje fibers, the fibrous tissue that conducts electrical impulses from the atrioventricular node to all parts of the ventricles of the heart. Other discoveries include Purkinje images, reflections of objects from structures of the eye, and the Purkinje shift, the change in the brightness of red and blue colors as light intensity decreases gradually at dusk. Purkyne was the first to use a microtome to make wafer thin slices of tissue for microscopic examination and was among the first to use an improved version of the compound microscope. He described the effects of camphor, opium, belladonna and turpentine on humans in 1829. He also experimented with nutmeg that same year, when he “washed down three ground nutmegs with a glass of wine and experienced headaches, nausea, euphoria, and hallucinations that lasted several days”, which remain a good description of today’s average nutmeg binge. Purkyne also discovered sweat glands in 1833 and published a thesis that recognized 9 principal configuration groups of fingerprints in 1823. Purkyne was also the first to describe and illustrate in 1838 the intracytoplasmic pigment neuromelanin in the substantia nigra. Purkyne also recognized the importance of the work of Eadweard Muybridge and constructed his own version of a stroboscope which he called forolyt. He put nine photos of him shot from various sides to the disc and entertained his grandchildren by showing them how he, an old and famous professor, is turning around at great speed.


In 1827, Purkyne married Julie Rudolphi, the daughter of a professor of physiology from Berlin. They had four children, two of whom were girls that died in early childhood. After 7 years of marriage, Julie died, leaving Purkyne with two young sons and in deep despair. Purkyne died on July 28, 1869, in Prague. He was buried in the cemetery for distinguished citizens near the Czech Royal Castle on Wyszehrad. Czechoslovakia issued two stamps in 1937 to commemorate the 150th anniversary of the birth of Purkinje (spelt Purkyne in Czech). The Masaryk University in Brno, Czech Republic, bore his name from 1960 to 1990, as did the standalone military medical academy in Hradec Kralove (1994-2004.) Today, a university in Ust? nad Labem bears his name: Jan Evangelista Purkyne University in Ust? nad Labem (Univerzita Jana Evangelisty Purkyne v Usti nad Labem.)


The crater Purkyne on the Moon is named after him, as is the asteroid 3701 Purkyne.


Sources:; Wikipedia


Enterococci May Have Evolved Antimicrobial Resistance Millions of Years Ago


Enterococci bacteria are the bane of hospitals, causing thousands of multidrug-resistant infections in patients each year. Now, according to an article published in the journal Cell (11 May 2017), evidence of the bacteria’s evolutionary history can be traced back to 425 million. The goal of the study was to understand why, among the vast diversity of gut flora, enterococci are so well adapted to the modern hospital environment. Results showed that based on molecular clock estimation, together with analysis of their environmental distribution, phenotypic diversity, and concordance with host fossil records, place the origins of the enterococci around the time of animal terrestrialization, 425-500 mya. Speciation appears to parallel the diversification of hosts, including the rapid emergence of new enterococcal species following the End Permian Extinction. Major drivers of speciation include changing carbohydrate availability in the host gut. Life on land would have selected for the precise traits that now allow pathogenic enterococci to survive desiccation, starvation, and disinfection in the modern hospital, foreordaining their emergence as leading hospital pathogens


The study examined DNA from 24 species of enterococci, taken from the guts of a wide variety of animal and human hosts. The authors calculated the average rate of genetic change within enterococcal species and compared genes of existing enterococci to those of related, non-enterococci bacteria. The analysis provided the ability to build an evolutionary timeline to estimate when key enterococci traits emerged. The authors then checked this timeline against the fossil record of terrestrial animal evolution. Results showed that all enterococci sampled were resistant to a common set of stresses — including antibiotics, disinfectants, drying and starvation –suggesting that the ancestors of all enterococci also shared these abilities. Enterococci appear to have developed these traits at around the same time that terrestrial animal life evolved. The authors theorized that the same traits that allow the bacteria to thrive in hospitals likely emerged when they were carried onto land in the guts of the world’s first terrestrial animals.


The authors noted that while the model is difficult to prove, it does partially explain the ability of enterococci to survive in hospital environments, as they have long been equipped to thrive in a wide range of challenging environments. According to the authors, having a better sense of what prompted the bacteria to evolve these abilities, could help control enterococci as the bacteria continue to circumvent hospital infection control methods.


Systemic Therapy Outperforms Intraocular Implant for Treating Uveitis


Uveitis is an inflammatory disease of the eye and the fifth leading cause of vision loss in the United States. Concerns about potential adverse effects of systemic corticosteroid and immunosuppressive therapy drove the development of an intraocular implant to treat uveitis locally. The fluocinolone intraocular implant, developed by Bausch & Lomb, was approved by the FDA in 2005. Early data suggested the implant was effective at controlling inflammation but had local ocular side effects. The Multicenter Uveitis Steroid Treatment Trial (MUST) was undertaken to evaluate whether the implant treatment was an improvement over systemic therapy for management of uveitis.


According to an article published online in JAMA (6 May 2017), after seven years, an NIH-funded clinical trial found that systemic therapy consisting of corticosteroids and immunosuppressants preserved vision of uveitis patients better — and had fewer adverse outcomes — than a long-lasting corticosteroid intraocular implant. Visual acuity, on average, remained stable among participants on systemic therapy but declined by an average of six letters (about one line on an eye chart) among participants who had the implant.


The study recruited 255 uveitis patients at 23 sites (21 in the U.S., one in the U.K., and one in Australia) and randomly assigned them to receive the fluocinolone implant or systemic treatment with corticosteroids (prednisone) and immunosuppressants (such as methotrexate or mycophenolate mofetil). While systemic corticosteroids, which are FDA-approved for treatment of uveitis, reduce acute inflammation effectively, they have potential systemic adverse effects when used at a high dose for a long time. The immunosuppressants, which are not FDA-approved for uveitis, inhibit pathological immune responses, thus reducing the amount of corticosteroids needed over the long-term, mitigating such side effects.


Through the first two years, the visual acuity remained about the same in the two groups (results published in 2011). However, at the end of the study, visual acuity on average remained stable in the systemic group but declined about six letters in the implant group. The authors found that implant-treated eyes also had reactivations of uveitis after about five years, which coincided with a decline in visual acuity. The loss of vision in the implant group appears to have been due to increased damage in the retina and choroid (a tissue rich in blood vessels lying underneath the retina).


With respect to side effects, patients in the implant group were more likely to develop ocular side effects like cataracts, intraocular pressure elevation that required treatment with medicine and often surgery, and glaucoma. Patients receiving systemic therapy had increased risk of needing treatment with antibiotics, possibly due to immunosuppression, but otherwise did not have large increases in the risk of adverse effects typically associated with systemic corticosteroids such as high blood pressure or diabetes.


FDA Clears New Device to Treat Esophageal Birth Defect in Babies


An estimated 1 in every 2,500 babies in the U.S. is born with esophageal atresia. Babies with this condition cannot feed normally, and they require a feeding tube until surgery can be performed to attach the esophagus to the stomach. Most babies born with esophageal atresia also have a tracheoesophageal fistula, which also needs to be repaired surgically, since fluids from the esophagus can get into the airways and interfere with breathing.


The FDA has authorized the use of the Flourish Pediatric Esophageal Atresia Anastomosis, a first-of-its-kind medical device to treat infants with esophageal atresia. The device uses magnets to pull the upper and lower esophagus together, closing the gap and allowing food to enter the stomach. It is not for use in infants who also have a tracheoesophageal fistula, an abnormal connection between the esophagus and the windpipe (trachea).


During the procedure to insert the Flourish device, doctors insert two catheters, one through the mouth and one through the stomach. The magnetic ends of the two catheters attract each other, and this attraction pulls the two ends of the esophagus together over several days, closing the gap and forming a connection. Once the catheters are removed, the infant can begin to feed by mouth.


The FDA reviewed data for the Flourish device through the humanitarian device exemption (HDE) process. A Humanitarian Use Device (HUD) is a device that is intended to benefit patients by treating or diagnosing a disease or condition that affects not more than 8,000 individuals in the U.S. per year. Data supporting the safety and probable benefit of the Flourish device include results from 16 patients who had the Flourish device implanted. In the limited data provided, all of the infants had a successful joining of their esophagus, with no remaining gap, within three to 10 days after receiving the device.  However, 13 of the 16 patients developed a complication which caused a narrowing in their esophagus (anastomotic stricture) that required a balloon dilation procedure, a stent or both to repair. Anastomotic strictures also occur from traditional surgery to repair the condition.


The Flourish device should not be used in patients older than one year, or who have teeth, which may damage the oral catheter. The device is also contraindicated in infants who have an existing tracheoesophageal fistula or who have esophageal segments that are more than 4 centimeters apart. Potential complications that may occur when the device is in place include ulceration or tissue irritation around the catheter implanted in the stomach and gum irritation due to pressure from the oral catheter. Potential long-term complications include gastroesophageal reflux. The device is manufactured and sold by Cook Medical.


Date Cookies Made with Three Healthy Ingredients

I’m experimenting by using dates instead of sugar, in recipes. It all started when our LA son, Alex, would visit and have his coffee with a couple of dates. He was right. This is a delicious combo. Take a bite of date, then a sip of coffee – lovely. So, then I wondered if a date cookie would also go well with a cup of coffee and began testing, plain date cookies, plus adding other ingredients, which all ends up, sharing this recipe with you. ©Joyce Hays, Target Health Inc.




1 cup almond flour

8 dates (pits removed)

1/4 tsp. vanilla extract


This is the easiest cookie recipe on the Planet. You can stick to the three ingredients, given, or you can add 1 additional ingredient from the following list: 1 heaping Tablespoon peanut butter (any brand you want, with or without peanuts); 1 and ? heaping Tablespoon shredded coconut (use the half for garnish); 1 and 1/2 Tablespoons white chocolate chips (use the half for garnishing); 1 and 1/2 Tablespoons plain walnuts (use the half for garnish) ©Joyce Hays, Target Health Inc.





1. Do any chopping, slivering, cutting, toasting, you need to do.


Chopping some garnishes at the same time: walnuts in one corner and white chocolate in the other. ©Joyce Hays, Target Health Inc.


Toasting pine nuts for top of cookies using peanut butter. You can toast plain peanuts also. Don’t need to use any nuts that come with salt. ©Joyce Hays, Target Health Inc.



2. Put parchment paper on a cookie sheet

3. Preheat oven to 350 degrees

4. Place all ingredients in a high speed blender, or food processor and blend until a dough like consistency is formed. If the dough is not sticky enough, keep blending until it sticks together.


Dates in food processor, next vanilla extract, then almond flour. Only pulse these three. Don’t add peanut butter or coconut, walnuts, white chocolate, etc. into the food processor. Add that fourth ingredient, later. ©Joyce Hays, Target Health Inc.



5. With a spatula, remove all the dough and put into a bowl. Now is the time to add your choice of a fourth ingredient, if you want. White chocolate chips are better added now, so they don’t get ground down too much. You control the size of the fourth ingredient, like walnuts and coconut, much better, if it’s added after the first three ingredients are pulsed in the food processor, and scraped in a mixing bowl. Feel free to experiment with that fourth ingredient. I tried banana but it didn’t work out too well.


The three contents of the food processor, were scraped into this bowl. ©Joyce Hays, Target Health Inc.


Here, 1 big Tablespoon of peanut butter is being added to the dough. It will get mixed until it’s completely combined with the other ingredients. ©Joyce Hays, Target Health Inc.


Here’s the peanut butter, now well incorporated into the dough. ©Joyce Hays, Target Health Inc.



6. Divide the dough into six pieces. Squeeze each portion in your hand, and roll into a ball.


In your hand, roll 1/6 of the dough into a ball. Then flatten it out. Make the rim of the cookie smooth, while it’s in your hand. Just push down a little, all around the rim, so there are no jagged edges. ©Joyce Hays, Target Health Inc.



7. In your hands, flatten each ball into a cookie shape and smooth the outer rim, as well.

8. Place cookies on the baking sheet, with parchment, and bake for 10 minutes, for a warm, just out of the oven cookie.


The walnut date cookies came out warm and delicious. ©Joyce Hays, Target Health Inc.


These are the white chocolate date cookies; they go fast! ©Joyce Hays, Target Health Inc.


All of the flavors are good, but these peanut butter date cookies are my favorites; One with a cup of coffee gives morning pleasure. ©Joyce Hays, Target Health Inc.


When Jules went to a conference in Iceland, last week, he took a whole container of the coconut date version, with him. ©Joyce Hays, Target Health Inc.


Mother’s Day flowers from our daughter, plus some icy Bellinis. Not bad, eh? ©Joyce Hays, Target Health Inc.


Hope everyone had a special Mother’s Day. It’s been a (welcome) cool Spring, here in the Big Apple.



From Our Table to Yours

Bon Appetit!


May 10, 2017

University of Minnesota College of Science and Engineering

Engineering researchers have developed a revolutionary process for 3D printing stretchable electronic sensory devices that could give robots the ability to feel their environment. The discovery is also a major step forward in printing electronics on real human skin.


Screenshot of video ( showing 3D printing of stretchable electronic sensory devices that could give robots the ability to feel their environment and is a major step forward in printing electronics on real human skin.
Credit: Shuang-Zhuang Guo and Michael McAlpine, University of Minnesota



Engineering researchers at the University of Minnesota have developed a revolutionary process for 3D printing stretchable electronic sensory devices that could give robots the ability to feel their environment. The discovery is also a major step forward in printing electronics on real human skin.

The research will be published in the next issue of Advanced Materials and is currently online.

“This stretchable electronic fabric we developed has many practical uses,” said Michael McAlpine, a University of Minnesota mechanical engineering associate professor and lead researcher on the study. “Putting this type of ‘bionic skin’ on surgical robots would give surgeons the ability to actually feel during minimally invasive surgeries, which would make surgery easier instead of just using cameras like they do now. These sensors could also make it easier for other robots to walk and interact with their environment.”

McAlpine, who gained international acclaim in 2013 for integrating electronics and novel 3D-printed nanomaterials to create a “bionic ear,” says this new discovery could also be used to print electronics on real human skin. This ultimate wearable technology could eventually be used for health monitoring or by soldiers in the field to detect dangerous chemicals or explosives.

“While we haven’t printed on human skin yet, we were able to print on the curved surface of a model hand using our technique,” McAlpine said. “We also interfaced a printed device with the skin and were surprised that the device was so sensitive that it could detect your pulse in real time.”

McAlpine and his team made the unique sensing fabric with a one-of-a kind 3D printer they built in the lab. The multifunctional printer has four nozzles to print the various specialized “inks” that make up the layers of the device — a base layer of silicone, top and bottom electrodes made of a conducting ink, a coil-shaped pressure sensor, and a sacrificial layer that holds the top layer in place while it sets. The supporting sacrificial layer is later washed away in the final manufacturing process.

Surprisingly, all of the layers of “inks” used in the flexible sensors can set at room temperature. Conventional 3D printing using liquid plastic is too hot and too rigid to use on the skin. These flexible 3D printed sensors can stretch up to three times their original size.

“This is a completely new way to approach 3D printing of electronics,” McAlpine said. “We have a multifunctional printer that can print several layers to make these flexible sensory devices. This could take us into so many directions from health monitoring to energy harvesting to chemical sensing.”

Researchers say the best part of the discovery is that the manufacturing is built into the process.

“With most research, you discover something and then it needs to be scaled up. Sometimes it could be years before it ready for use,” McAlpine said. “This time, the manufacturing is built right into the process so it is ready to go now.”

The researchers say the next step is to move toward semiconductor inks and printing on a real body.

“The possibilities for the future are endless,” McAlpine said.

In addition to McAlpine, the research team includes University of Minnesota Department of Mechanical Engineering graduate students Shuang-Zhuang Guo, Kaiyan Qiu, Fanben Meng, and Sung Hyun Park.

The research was funded by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (Award No. 1DP2EB020537). The researchers used facilities at the University of Minnesota Characterization Facility and Polymer Characterization Facility for testing.

Story Source:

Materials provided by University of Minnesota College of Science and Engineering. Note: Content may be edited for style and length.

Journal Reference:

  1. Shuang-Zhuang Guo, Kaiyan Qiu, Fanben Meng, Sung Hyun Park, Michael C. McAlpine. 3D Printed Stretchable Tactile Sensors. Advanced Materials, 2017; 1701218 DOI: 10.1002/adma.201701218


Source: University of Minnesota College of Science and Engineering. “3D-printed ‘bionic skin’ could give robots the sense of touch.” ScienceDaily. ScienceDaily, 10 May 2017. <>.

May 10, 2017

University of Illinois at Urbana-Champaign

Scientists report that they now know how to build a molecular Trojan horse that can penetrate gram-negative bacteria, solving a problem that for decades has stalled the development of effective new antibiotics against these increasingly drug-resistant microbes.


6DNM-amine is a proof of concept that the new approach can transform gram-positive antibiotics to drugs that can also kill gram-negative microbes.



Scientists report that they now know how to build a molecular Trojan horse that can penetrate gram-negative bacteria, solving a problem that for decades has stalled the development of effective new antibiotics against these increasingly drug-resistant microbes. The findings appear in the journal Nature.

Led by University of Illinois chemistry professor Paul Hergenrother, the scientists tested their approach by modifying a drug that kills only gram-positive bacteria, which lack the rugged outer cell membrane that characterizes gram-negative microbes and makes them so difficult to combat. The modifications converted the drug into a broad-spectrum antibiotic that could also kill gram-negatives, the team reports.

Gram-negative bacteria include pathogenic strains of Escherichia coli, Acinetobacter, Klebsiella and Pseudomonas aureginosa, all of which, according to the Centers for Disease Control and Prevention, are becoming “increasingly resistant to most available antibiotics.”

The effort to find new antibiotics to combat these pathogens has failed again and again simply because almost all new drugs are unable to penetrate the gram-negative bacterial cell wall, Hergenrother said.

“We have a handful of classes of antibiotics that work against gram-negatives, but the last class was introduced 50 years ago, in 1968,” Hergenrother said. “Now, the bacteria are developing resistance to all of them.”

The void of new antibiotics is not due to lack of effort. In 2007, for example, a large pharmaceutical company screened roughly 500,000 synthetic compounds for activity against E. coli, none of which led to a new drug, the researchers wrote.

“These microbes have an outer membrane that is basically impermeable to antibiotics or would-be antibiotics,” Hergenrother said. “Any drugs that work against them almost always are going through a special gateway, called a porin, that lets in amino acids and other compounds the bacteria need to live.”

Rather than using commercial chemical libraries, Hergenrother’s group turned to its own collection of complex molecules. These were the natural products of plants and microbes that the scientists had modified in the lab.

“A few years ago, we found that through a series of organic chemistry steps we could change natural products into molecules that look very different from the parent compounds,” Hergenrother said. The new molecules were more diverse than most available commercially, he said. The team has produced more than 600 new compounds using this approach.

The researchers tested these compounds individually against gram-negative bacteria, looking for those that successfully accumulated inside the cells.

“The few that got in all had amines on them, so we started building out from there,” Hergenrother said. Amines are molecular components that contain the element nitrogen.

The researchers tested more compounds with amines, and their success rate increased. But this was not the only trait needed to break into the gram-negative cells.

“Having an amine was necessary but not sufficient,” Hergenrother said.

Using a computational approach, the team discovered three key traits required for access: To get in, a compound must have an amine that is not hindered by other molecular components; it must be fairly rigid (floppy compounds are more likely to get stuck in the porin gateway), and it must have “low globularity,” which, more simply, means it must be flat, not fat.

To test these guidelines, the team added an amine group to deoxynybomycin, a compound created in the 1960s by Kenneth Rinehart Jr., at the time a chemistry professor at the U. of I. They chose this compound because it is a potent killer of gram-positive bacteria and has the other desirable traits: rigidity and low globularity. By adding an amine to the right place on the molecule, the researchers converted DNM into a broad-spectrum antibiotic that they are calling 6DNM-amine.

“The point is not necessarily this compound, which may or may not be a good candidate as a drug used in human health,” Hergenrother said. “It’s more important as a demonstration that we understand the fundamentals at play here. Now, we know how to make collections of compounds where everything gets in.”

Finding compounds that penetrate the membrane is important, but antibiotics also must kill the bacteria. Previous research suggests that only about one in 200 random compounds that penetrate gram-negative bacteria are also likely to kill the bacteria, Hergenrother said.

“These are workable odds,” he said. “Much better than zero in 500,000.”

Story Source:

Materials provided by University of Illinois at Urbana-Champaign. Original written by Diana Yates. Note: Content may be edited for style and length.

Journal Reference:

  1. Michelle F. Richter, Bryon S. Drown, Andrew P. Riley, Alfredo Garcia, Tomohiro Shirai, Riley L. Svec, Paul J. Hergenrother. Predictive compound accumulation rules yield a broad-spectrum antibiotic. Nature, 2017; DOI: 10.1038/nature22308



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