April 18, 2017

Karolinska Institutet

One of the most common combined oral contraceptive pills has a negative impact on women’s quality of life but does not increase depressive symptoms. This is shown by a major randomized, placebo-controlled study.


Birth control pills. Both general quality of life and specific aspects like mood/well-being, self-control and energy level were affected negatively by oral contraceptives.
Credit: © Jacob Kearns / Fotolia



One of the most common combined oral contraceptive pills has a negative impact on women’s quality of life but does not increase depressive symptoms. This is shown by a major randomised, placebo-controlled study conducted by researchers at Karolinska Institutet in Sweden in collaboration with the Stockholm School of Economics. The results have been published in the scientific journal Fertility and Sterility.

“Despite the fact that an estimated 100 million women around the world use contraceptive pills we know surprisingly little today about the pill’s effect on women’s health. The scientific base is very limited as regards the contraceptive pill’s effect on quality of life and depression and there is a great need for randomised studies where it is compared with placebos,” says professor Angelica Lindén Hirschberg at the Department of Women’s and Children’s Health at Karolinska Institutet.

She has led just such a study together with Niklas Zethraeus, associate professor at the Department of Learning, Informatics, Management and Ethics, Anna Dreber Almenberg from the Stockholm School of Economics, and Eva Ranehill of the University of Zürich. 340 healthy women aged between 18 and 35 were treated randomly over the course of three months with either pills with no effect (placebos) or contraceptive pills containing ethinylestradiol and levonorgestrel, the most common form of combined contraceptive pill in Sweden and many other countries. Neither the leaders of the experiment nor the subjects knew which treatment was given to which women.

The women who were given contraceptive pills estimated their quality of life to be significantly lower than those who were given placebos. Both general quality of life and specific aspects like mood/well-being, self-control and energy level were affected negatively by the contraceptives. On the other hand, no significant increase in depressive symptoms was observed.

Since the changes were relatively small, the results must be interpreted with a certain amount of caution, the researchers emphasise. In the case of individual women, however, the negative effect on quality of life may be of clinical importance.

“This might in some cases be a contributing cause of low compliance and irregular use of contraceptive pills. This possible degradation of quality of life should be paid attention to and taken into account in conjunction with prescribing of contraceptive pills and when choosing a method of contraception,” says Niklas Zethraeus.

The type of combined contraceptive pill that was used in the study (etinylestradiol + levonorgestrel) is recommended in many countries as the first choice since it is considered to entail the least risk of thrombosis among the combined contraceptive pills. The findings from the study cannot be generalised to other kinds of combined contraceptive pills because they may have a different risk profile and side-effects.

Story Source:

Materials provided by Karolinska Institutet. Note: Content may be edited for style and length.

Journal Reference:

  1. Niklas Zethraeus, Anna Dreber, Eva Ranehill, Liselott Blomberg, Fernand Labrie, Bo von Schoultz, Magnus Johannesson, Angelica Lindén Hirschberg. A first choice combined oral contraceptive influences general well-being in healthy women – a double-blind, randomized, placebo-controlled trial. Fertility and Sterility, 2017 DOI: 10.1016/j.fertnstert.2017.02.120


Source: Karolinska Institutet. “Oral contraceptives reduce general well-being in healthy women.” ScienceDaily. ScienceDaily, 18 April 2017. <>.

April 17, 2017

Mount Sinai Health System

The sympathetic nervous system, not white blood cells, are critically important in the regulation of energy expenditure and thermogenesis, researchers reveal in a new report.


While researchers had previously hypothesized that macrophages, a class of white blood cells, played a major role in thermogenesis, the new study suggests that the main driver of thermogenesis is the sympathetic nervous system, which is chiefly controlled by the brain. (Stock image)
Credit: © highwaystarz / Fotolia



A new study from the Icahn School of Medicine at Mount Sinai provides important insights into how the body regulates its production of heat, a process known as thermogenesis that is currently intensely studied as a target of diabetes and obesity treatment in humans.

While researchers had previously hypothesized that macrophages, a class of white blood cells, played a major role in thermogenesis, the new study suggests that the main driver of thermogenesis is the sympathetic nervous system, which is chiefly controlled by the brain. The results were published online in Nature Medicine.

The Mount Sinai research team led by Christoph Buettner, MD, PhD, senior author of the study and Professor of Medicine (Endocrinology, Diabetes, and Bone Disease) at the Icahn School of Medicine at Mount Sinai, focused on catecholamines, hormones released by the sympathetic nervous system to activate brown fat tissue. Brown adipose tissue is a type of fat tissue that burns energy to produce heat and keep us warm. Catecholamines can also convert white fat tissue, the more familiar kind of fat tissue that stores lipids, into a tissue that resembles brown fat. The researchers tested whether macrophages could provide an alternative source of catecholamines, as had been proposed in recent years.

“Thermogenesis is a metabolic process that receives a lot of interest as a target of drugs that allow you to burn energy and hence reduce obesity and improve diabetes. It turns out that macrophages are not that important, as they are unable to make catecholamines, but clearly the brain through the sympathetic nervous system is,” says Dr. Buettner. “Therefore, it is very important to study the role of the brain and the sympathetic nervous system when it comes to understanding metabolism.”

The ability to generate heat is critical for the survival of warm-blooded animals, including humans, as it prevents death by hypothermia. “This evolutionary pressure shaped the biology of humans and that of other warm-blooded animals, and may in part explain why humans are susceptible to developing diabetes in the environment in which we live,” says Dr. Buettner.

According to Dr. Buettner, while a lot of effort has been invested in targeting the immune system to cure diabetes and insulin resistance, as of yet there are no anti-inflammatory drugs that have been shown to work well in humans with metabolic disease. “Our study suggests that perhaps the key to combating the devastating effects of diabetes and obesity in humans is to restore the control of thermogenesis and metabolism by the brain and the autonomic nervous system,” says Dr. Buettner.

Story Source:

Materials provided by Mount Sinai Health System. Note: Content may be edited for style and length.

Journal Reference:

  1. Katrin Fischer, Henry H Ruiz, Kevin Jhun, Brian Finan, Douglas J Oberlin, Verena van der Heide, Anastasia V Kalinovich, Natasa Petrovic, Yochai Wolf, Christoffer Clemmensen, Andrew C Shin, Senad Divanovic, Frank Brombacher, Elke Glasmacher, Susanne Keipert, Martin Jastroch, Joachim Nagler, Karl-Werner Schramm, Dasa Medrikova, Gustav Collden, Stephen C Woods, Stephan Herzig, Dirk Homann, Steffen Jung, Jan Nedergaard, Barbara Cannon, Matthias H Tschöp, Timo D Müller, Christoph Buettner. Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis. Nature Medicine, 2017; DOI: 10.1038/nm.4316


Source: Mount Sinai Health System. “Your brain, not your white blood cells, keeps you warm, new study suggests.” ScienceDaily. ScienceDaily, 17 April 2017. <>.

BIOMED 2017 Conference – Tel-Aviv (May 23-25, 2017)


Target Health will again be attending the 16th MIXiii-BIOMED 2017 Conference and Exhibition, being held at the David Intercontinental, (May 23-25, 2017) in Tel-Aviv. This is the 16th anniversary of the conference which we have been attending since 2009. We have many clients and friends in Israel, so please let us know if you will be attending. We look forward to getting together and having a coffee.


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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Dopamine Labs May Know How To Break Your Addiction to Technology (a movement to align technology with our humanity)

Ball-and-stick model of the dopamine molecule, a neurotransmitter that affects the brain’s reward and pleasure centers. Color code: Carbon, C: black; Hydrogen, H: white; Oxygen, O: red; Nitrogen, N: blue. This file is made available under the Creative Commons CC0 1.0 Universal Public Domain Dedication



In the brain, dopamine functions as a neurotransmitter – a chemical released by 1) ___ (nerve cells) to send signals to other nerve cells. The brain includes several distinct dopamine pathways, one of which plays a major role in reward-motivated behavior. Most types of rewards increase the level of dopamine in the brain, and many addictive drugs increase dopamine neuronal activity. Other brain dopamine pathways are involved in motor 2) ___ and in controlling the release of various hormones. These pathways and cell groups form a dopamine system which is neuromodulatory. Outside the central nervous system, dopamine functions primarily as a local chemical messenger. In blood vessels, it inhibits norepinephrine release and acts as a vasodilator (at normal concentrations); in the kidneys, it increases sodium excretion and urine output; in the pancreas, it reduces 3) ___ production; in the digestive system, it reduces gastrointestinal motility and protects intestinal mucosa; and in the immune system, it reduces the activity of lymphocytes. With the exception of the blood vessels, dopamine in each of these peripheral systems is synthesized locally and exerts its effects near the cells that release it.


Company Overview


Dopamine Labs, Inc. develops and delivers an application programming interface (API) that enables developers to reinforce users for their applications. Its API enables an application to hack user engagement and retention using models from neuroscience to tell that application when to reinforce a user at that moment. Addiction to technology can be like a drug 4) ___ .It’s not an accident – it’s by design. Dopamine Labs Inc., thought leaders in the mind hijacking industry, wants to equip you with the tools to reclaim your brain. Based out of Southern California, the team of five self-described coders, machine learners, brain architects, designers and hustlers, push persuasive computing? – ?technology that shapes our behavior – ?to the limits. The company provides two apps at the opposite ends of the mind hijacking spectrum: On one end is Space, an app that helps curb compulsive checking – ?like mindlessly opening and scrolling through Facebook? – ?by delaying instant 5) ___. On the other end is Dopamine, an app that helps keep users hooked. It plugs a line of code into an existing app and doles out rewards at just the scientifically-proven right moment to encourage habit building and keep you coming back for more. If Dopamine is turning the mind hijacking knob up to eleven, Space equips people with the capacity to turn it down and regain control over their 6) ___. The apps from Dopamine Labs fulfill dual needs: Their niche knowledge of neuroscience and neuroinformatics (how the brain makes decisions) is lucrative on the marketing side. Companies, eager for this intel, want to know how to better hone their users’ behaviors and persuade them to stay engaged.


Recent research suggests that being constantly plugged in? – ?especially when multitasking on different gadgets, or toggling between apps – ?has a profound impact on our 7) ___. A Stanford University study published last year found that chronic media multitaskers had a harder time remembering both distant and recent events. Dopamine, on the other hand, can help app-makers vie for our already scattered attention span, while the Space app is a way of making behaviors, like automatically logging on to Instagram, more mindful. As Ramsay Brown, COO and founder of Dopamine Labs, tells Thrive Global, We built our Space app because, in the bigger picture of what can be built here in persuasive technology, we can use the same techniques, the machine learning and neuroscience, to help people start behaviors that they want to start?but also to help people sustain habits, decrease behaviors they don’t like, and help people stop things entirely. With the Space version of Snapchat, for instance, you’ll get a breathing prompt before you can enter the app. The fancy neuroscience term for this is adaptive stimulus devaluation, which basically means making something desirable (like compulsively checking Snapchat) less appealing by delaying gratification. But Space isn’t about punishing or shaming you for using your favorite apps. It’s about giving you the opportunity to consider what you really want and giving you a choice to disconnect. Creating a time delay between you and the prize makes the prize less valuable, and it quells the itch we’re scratching with social media. The crux, of course, is that itch we’re scratching is a temporary fix: odds are we’re scrolling through social 8) ___ because we’re bored or stressed, but with so many little gratification escape pods, as Brown calls them, we’re able to avoid thinking about what we really need. In other words, we get to ignore “that thing that just itched in my soul, Brown says.


Dopamine Labs occupies a unique, and morally hazy, role at such opposite poles of the brain-hacking spectrum. But in launching both Dopamine and Space, Brown explains that the company can set the tone for how this technology can be used, rather than tell people how to use it. We’re not interested as much in being the thought police and telling people what they should want, or what kinds of brain they should aspire to create and live inside, as much as arming them with the tools that enable them to do that just as well. Brown argues that transparency around mind hijacking, and understanding how this is already happening to us all of the time, is essential to creating more mindful relationships with technology. Even knowing that the brain is incredibly malleable, Brown, who studied neuroscience at the University of Southern California (where he met future Dopamine Labs co-founder T. Dalton Combs, then studying neuroeconomics), was surprised at how we can’t resist our favorite apps. He tells TG he knew the raw science of this, but “the skeptic in me said No, no, what about freedom and dignity and autonomy and self-determination? Our proclivity to constantly check social media isn’t because of weak willpower, Brown says. [Our brains are] changing per the design?of whatever data team at these companies are desiring you to change into. So they’re using mathematical and artificial 9) ___ techniques to control, very carefully, in an experimental manner, when and how you’re shown different things, when and how you’re given your likes.


In the digital world, we’re actually not the customer, Brown says. “We don’t pay for Facebook. We don’t pay for Twitter or Instagram. If you’re not paying for it, you are not the customer, he says. You’re the goods being sold. How do you like that? Repeating for emphasis: Humans are the goods being sold. Big brands are the customers while our attention span, and our consumer preferences, are the things to be auctioned off. Technology is changing faster than our brains can keep up. Being transparent about how 10) ___ changes the brain, and using tools that can help redirect this, is the first step in chipping away at unhealthy habits, ones that aren’t even of our own creation. Dopamine and Space apps are intended to help catalyze our brains’ evolution. The very same things that are troubling, like the ways technology already hijacks our brains – or how malleable our brains are to these suggestions – gives Brown hope. Technology is not a tool for crushing the human spirit, Brown says, but for lifting it up.


Overview by Dopamine Labs


Dopamine Labs


Short review of dopamine and serotonin


TED Talk by former Google ethicist: How better tech could protect us from distraction


Short review of how Tech becomes addictive


ANSWERS: 1) neurons; 2) control; 3) insulin; 4) addiction; 5) gratification; 6) minds; 7) brains; 8) media; 9) intelligence; 10) technology


Arvid Carlsson MD (1923 to Present) and Still Going Strong at 94!

Editor’s note: Short background


Kathleen Montagu (died 28 March 1966) was the first researcher to identify dopamine in human brains. Working in Hans Weil-Malherbe’s laboratory at the Runwell Hospital outside London, the presence of dopamine was identified by paper chromatography in the brain of several species, including a human brain. Her research was published in August 1957, followed and confirmed by Hans Weil-Malherbe in November 1957.


Nobel Prize-rewarded Arvid Carlsson to be the first researcher to identify that dopamine is a neurotransmitter. His research was published in November 1957, along with colleagues Margit Linsqvist and Tor Magnusson.


Arvid Carlsson (born 25 January 1923) is a Swedish neuropharmacologist who is best known for his work with the neurotransmitter dopamine and its effects in Parkinson’s disease. For his work on dopamine, Carlsson was awarded the Nobel Prize in Physiology or Medicine in 2000, along with American co-recipients Eric Kandel at Columbia University and Paul Greengard at Rockefeller. Carlsson was born in Uppsala, Sweden, son of Gottfrid Carlsson, historian and later professor of history at the Lund University, where he began his medical education in 1941. In 1944 he was participating in the task of examining prisoners of Nazi concentration camps, whom Folke Bernadotte, a member of the royal Swedish family, had managed to bring to Sweden. Although Sweden was neutral during World War II, Carlsson’s education was interrupted by several years of service in the Swedish Armed Forces. In 1951, he received his M.L. degree and his M.D. He then became a professor at the University of Lund. In 1959 he became a professor at the University of Gothenburg.


In 1957 Kathleen Montagu succeeded in demonstrating the presence of dopamine in the human brain; later that same year Carlsson also demonstrated that dopamine was a neurotransmitter in the brain and not just a precursor for norepinephrine. Carlsson went on to developed a method for measuring the amount of dopamine in brain tissues. He found that dopamine levels in the basal ganglia, a brain area important for movement, were particularly high. He then showed that giving animals the drug reserpine caused a decrease in dopamine levels and a loss of movement control. These effects were similar to the symptoms of Parkinson’s disease. By administering to these animals L-Dopa, which is the precursor of dopamine, he could alleviate the symptoms. These findings led other doctors to try using L-Dopa on patients with Parkinson’s disease, and found it to alleviate some of the symptoms in the early stages of the disease. L-Dopa is still the basis for most commonly used means of treating Parkinson’s disease.


While working at Astra AB, Carlsson and his colleagues were able to derive the first marketed selective serotonin reuptake inhibitor, zimelidine, from brompheniramine. Zimelidine preceded both Fluoxetine (Prozac) and Fluvoxamine as the first SSRI, but was later withdrawn from the market due to rare cases of Guillain-Barre syndrome.


Still an active researcher and speaker at over 90 years of age, Carlsson, together with his daughter Maria, is working on OSU6162, a dopamine stabilizer alleviating symptoms of post-stroke fatigue.



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Rates of New Diagnosed Cases of Type 1 and Type 2 Diabetes Rising


In the United States, 29.1 million people are living with diagnosed or undiagnosed diabetes, and about 208,000 people younger than 20 years are living with diagnosed diabetes.


Type 1 diabetes, the most common form of diabetes in young people, is a condition in which the body fails to make insulin. Causes of type 1 diabetes are still unknown. However, disease development is suspected to follow exposure of genetically predisposed people to an “environmental trigger,“ stimulating an immune attack against the insulin-producing beta cells of the pancreas. Thus, Type 1 diabetes can be considered an autoimmune disease.


In type 2 diabetes, the body does not make or use insulin well. In the past, type 2 diabetes was extremely rare in youth, but it has become more common in recent years.


According to an article published in the New England Journal of Medicine (13 April 2017), rates of new diagnosed cases of type 1 and type 2 diabetes are increasing among youth in the United States. This study is the first ever to estimate trends in new diagnosed cases of type 1 and type 2 diabetes in youth (those under the age of 20), from the five major racial/ethnic groups in the U.S.: non-Hispanic whites, non-Hispanic blacks, Hispanics, Asian Americans/Pacific Islanders, and Native Americans. However, the Native American youth who participated in the SEARCH for Diabetes in Youth study are not representative of all Native American youth in the United States. Thus, these rates cannot be generalized to all Native American youth nationwide.


The study found that from 2002 to 2012, incidence, or the rate of new diagnosed cases of type 1 diabetes in youth increased by about 1.8% each year. During the same period, the rate of new diagnosed cases of type 2 diabetes increased even more quickly, at 4.8%. The study included 11,244 youth ages 0-19 with type 1 diabetes and 2,846 youth ages 10-19 with type 2.


The study results reflect the nation’s first and only ongoing assessment of trends in type 1 and type 2 diabetes among youth and help identify how the epidemic is changing over time in Americans under the age of 20 years.




— Across all racial/ethnic groups, the rate of new diagnosed cases of type 1 diabetes increased more annually from 2003-2012 in males (2.2%) than in females (1.4%) ages 0-19.


— Among youth ages 0-19, the rate of new diagnosed cases of type 1 diabetes increased most sharply in Hispanic youth, a 4.2% annual increase. In non-Hispanic blacks, the rate of new diagnosed cases of type 1 diabetes increased by 2.2% and in non-Hispanic whites by 1.2% per year.


— Among youth ages 10-19, the rate of new diagnosed cases of type 2 diabetes rose most sharply in Native Americans (8.9%), Asian Americans/Pacific Islanders (8.5%) and non-Hispanic blacks (6.3%). Note: The rates for Native Americans cannot be generalized to all Native American youth nationwide.


— Among youth ages 10-19, the rate of new diagnosed cases of type 2 diabetes increased 3.1% among Hispanics. The smallest increase was seen in whites (0.6%).


— The rate of new diagnosed cases of type 2 diabetes rose much more sharply in females (6.2%) than in males (3.7%) ages 10-19.




Several NIH-funded studies are directly examining how to delay, prevent, and treat diabetes:


— Type 1 Diabetes TrialNet <>screens thousands of relatives of people with type 1 diabetes annually and conducts prevention studies with those at highest risk for the disease.


— The Environmental Determinants of Diabetes in the Young (TEDDY) study seeks <> to uncover factors that may increase development of type 1 diabetes.


— For youth with type 2 diabetes, the ongoing Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) <> study is examining methods to treat the disease and prevent complications.


Additionally, CDC’s NEXT-D study <> aims to understand how population-targeted policies affect preventive behaviors and diabetes outcomes and answer questions about quantity and quality of care used, costs, and unintended consequences.


Gene Silencing Shows Promise for Treating 2 Fatal Neurological Disorders


In 1996, it was discovered that mutations in the ataxin 2 gene cause spinocerebellar ataxia type 2 (SCA2), a fatal inherited disorder that primarily damages a part of the brain called the cerebellum, causing patients to have problems with balance, coordination, walking and eye movements.


Mutations in ataxin 2 that are associated with SCA2 cause the gene to have polyglutamine expansions, strings of repeated copies of the three letter genetic code, CAG, which stands for the amino acid glutamine. On average, symptoms appear earlier and are more severe for patients who have longer strings. People who have only 27-33 repeats will not develop SCA2 but have an increased risk for ALS.


Now, in two studies of mice, reported in Nature (12 April 2017), it was shown that a drug, engineered to combat the gene that causes SCA2, might also be used to treat amyotrophic lateral sclerosis (ALS), a paralyzing and often fatal disorder. For the study, it was found that the problems associated with SCA2, could be reduced by injecting mouse brains with a drug programmed to silence the ataxin 2 gene. In the second study, it was showed that injections of the same type of drug into the brains of mice prevented early death and neurological problems associated with ALS. The type of drug used is called an antisense oligonucleotide. Like an incomplete row of teeth on a zipper, these drugs are short sequences of DNA designed to bind to a portion of a gene’s instructions carried by a molecule called messenger RNA. This stops cells from manufacturing proteins, a process known as gene silencing.


An antisense oligonucleotide drug has been approved by the FDA for treating spinal muscular atrophy, a hereditary disorder that causes arm and leg muscle weakness and deterioration in children. Early phase clinical trials are being conducted on the safety and effectiveness of gene silencing drugs to treat several neurological disorders, including Huntington’s disease and an inherited form of ALS.


The authors worked with a pharmaceutical company to develop antisense oligonucleotides that silence the ataxin 2 gene rather than the CAG repeats. They then tested oligonucleotides on two lines of mice genetically engineered to have problems associated with SCA2 by programming neurons in the cerebellum to make mutant ataxin 2. In both lines, the oligonucleotides appeared to be effective. Mice injected with the drug were able to walk on a rotating rod longer than mice that received a placebo. Electrical recordings showed the drug restored the firing patterns of neurons in the cerebellum to normal. In addition to reducing ataxin 2 gene levels, the researchers found that the drug also restored the levels of several genes that appear to be decreased by mutant ataxin 2.


Meanwhile, authors used different mice to test the idea of combating ALS by silencing ataxin 2. These mice were genetically modified to manufacture high levels of the human version of TDP-43, a protein that normally regulates genes. The researchers investigated these mice because neurons from ALS patients often contain toxic clusters of TDP-43. The mice rapidly develop problems with walking and die early. Previous studies on yeast and flies by Dr. Gitler’s team and his collaborators have suggested that mutant ataxin 2 may control the toxicity of TDP-43. Compared to placebo, injections of the antisense oligonucleotides into the nervous system of the newborn mice extended their median lifespan by 35 percent and improved their ability to walk, while lowering ataxin 2 gene levels in the brain and spinal cord.


The authors saw similar results when they eliminated ataxin 2 by crossbreeding the TDP-43 mice with mice that are genetically programmed to have no ataxin 2 gene. The offspring lived longer and walked better than the TDP-43 mice. The brains of the offspring also had fewer toxic TDP-43 clusters than the TDP-43 mice.


Drug Approved to Treat Tardive Dyskinesia


Tardive dyskinesia is a neurological disorder characterized by repetitive involuntary movements, usually of the jaw, lips and tongue, such as grimacing, sticking out the tongue and smacking the lips. Some affected people also experience involuntary movement of the extremities or difficulty breathing. Tardive dyskinesia is a serious side effect sometimes seen in patients who have been treated with antipsychotic medications, especially the older medications, for long periods to treat chronic conditions, such as schizophrenia and bipolar disorder. Tardive dyskinesia can also occur in patients taking antipsychotic medications for depression and certain medications for gastrointestinal disorders and other conditions. It is unclear why some people who take these medications develop tardive dyskinesia yet others do not.


The FDA has approved Ingrezza (valbenazine) capsules to treat adults with tardive dyskinesia. This is the first drug approved by the FDA for this condition. The efficacy of Ingrezza was shown in a clinical trial of 234 participants that compared Ingrezza to placebo. After six weeks, participants who received Ingrezza had improvement in the severity of abnormal involuntary movements compared to those who received placebo. Ingrezza may cause serious side effects including sleepiness and heart rhythm problems (QT prolongation). Its use should be avoided in patients with congenital long QT syndrome or with abnormal heartbeats associated with a prolonged QT interval. Those taking Ingrezza should not drive or operate heavy machinery or do other dangerous activities until it is known how the drug affects them.


The FDA granted Neurocrine Biosciences, Inc. Fast Track, Priority Review and Breakthrough Therapy designations for this program.


Another Holiday Dessert: White Chocolate/Marzipan with a Cashew Kiss Inside

First I ordered the little candy flowers, you see above, from Amazon and then stored in back of fridge. I knew I would think of a use for them. When Spring arrived to Manhattan and hardy little flowers started peeping through the soil, I thought of the stored decorations; they seemed to call out for white chocolate rather than dark. Gradually, this recipe fell into place. The concept and preparation were fun and easy to do. Naturally, I then wanted to share the results with you. ©Joyce Hays, Target Health Inc.


This is a perfect holiday dessert. If you wanted a different garnish like cashew crumbs or tiny pieces of shaved chocolate, or whatever you have around the house, that would work also. With this batch, because Spring had arrived, I liked the little flowers. ©Joyce Hays, Target Health Inc.


A little bite of heaven. ©Joyce Hays, Target Health Inc.



Filling Ingredients


1 and 1/2 cups toasted salt-free cashews (bought at

3 Tablespoons Grade A or B maple syrup (bought at

1/2 teaspoon bourbon vanilla extract (bought at

pinch of salt

3 Tablespoons white chocolate chips (FreshDirect)


Coating & Dipping Ingredients


3.5 ounces of a white chocolate brick (bought at Whole Foods)

1 can marzipan (bought online at

Use any type of garnish you want like: crumbs of cashew, tiny pieces of shaved dark chocolate, teeny candy flowers, rainbow sprinkles (buy in a small bottle), rum soaked pieces of cherry


Online buying, makes life so easy. For these ingredients, I went to three websites: FreshDirect, Amazon and ©Joyce Hays, Target Health Inc.




1. Take out a plate or small platter, and put parchment paper on the plate. You will put little dough balls on this plate and into the fridge for 60 minutes.

2. Plan your garnish and have it ready to sprinkle over the melted chocolate before it hardens. It’s too late to do this, once the chocolate has hardened.


Garnish is ready. ©Joyce Hays, Target Health Inc.



3. In a blender, combine all filling ingredients, except white chocolate chips, until cashews are broken down into a batter which holds together when pressed. Pulse for 30 seconds or more, if needed. Remove the batter to a bowl.


The cashews are in the food processor, with maple syrup, vanilla extract and pinch of salt. ©Joyce Hays, Target Health Inc.


Now, keep pulsing until the cashews, vanilla, maple syrup, salt, turn into a batter. ©Joyce Hays, Target Health Inc.



4. After scraping all of the batter into a bowl, now, stir in the white chocolate chips.


With a spatula, scrape out of your food processor, every last bit of the cashew dough into a regular mixing bowl (not with electric beaters). Add the white chocolate bits to the dough and mix them into the dough, with your hands. ©Joyce Hays, Target Health Inc.



5. Using your hands roll the dough into 13 to 15 half-inch balls, and place on a parchment lined plate.


Here is what a cashew dough ball looks like. (with white chocolate chips) ©Joyce Hays, Target Health Inc.


More cashew dough balls on parchment, eventually going into fridge for 60 minutes. ©Joyce Hays, Target Health Inc.



6. Put in freezer for at least 30 to 60 minutes.

7. While dough is freezing, roll out the can of marzipan. Using a cookie cutter or small round glass or cup, press the circle into the marzipan until you have 13“ to 15“ circles, thick enough to hold the dough, but not so thin that the marzipan pouch will break when the dough is put into it. There will be little scraps of the marzipan, so save them until you have enough to make another circle. Make marzipan circles that equal the number of cashew dough balls you’ve made.

8. After 60 minutes, you will place a dough ball in the center of a marzipan circle. Then with your fingers, gather the marzipan up and over the dough ball. The marzipan is easy to manipulate, so when you’ve covered the dough ball with marzipan, simply pinch it, at the top a little, and the marzipan will be sealed. You’re now ready to dip all the balls into warm white chocolate.


Marzipan has been rolled out with a wooden rolling pin. I didn’t have any cookie cutters, so I used this round dish that I use on the table to serve little extras like more anchovies for Caesar Salad, or more salmon roe for top of baked potato. Your marzipan circle should be large enough to wrap around one cashew dough ball. ©Joyce Hays, Target Health Inc.



9. In a double boiler, or small pan, melt the white chocolate.


I like to use this tiny frying pan to melt chocolate because it’s easier to use my hands to dip the balls into. ©Joyce Hays, Target Health Inc.


Here is the one stage of this recipe that you might balk at. Now, the time has come to dip the balls into the warm melted chocolate. You can do it by putting one ball at a time, into the chocolate, with your fingers. Roll it around to get completely covered, using fingers or a fork. Then remove the wet chocolate ball with fingers or with two forks, and put it on the plate you have ready with the parchment. If you’re quick, you can do this with half of your balls, and then add the sprinkles right away, to be sure they will stick. The thing is, what do you do with your sticky chocolate fingers?     :))  Guess. That’s right.



10. After the freezing time is up, remove the dough. Put one piece of the cashew dough in the middle of a marzipan circle. With your fingers, gather the outer circle of marzipan around the dough, so that the marzipan can be pinched together at the top like a little purse.

11. Have the same plate with parchment ready.

12. Pick up each little marzipan purse or ball and dip it into the melted chocolate; roll it around so you get as much of it covered as possible, then put the cashew kiss on the plate. Use your fingers or use two forks.

13. Immediately sprinkle the white balls with whatever garnish you have ready. Do this while the chocolate is still wet. Later, the sprinkle will not stick, as well.

14. Do the dipping and sprinkling, one at a time, with each little chocolate purse, putting each one to harden on the plate. Or, as mentioned, above, do the dipping fast and get half, or all on the plate and then do your garnishing, quickly while the chocolate is still wet and not yet hardened.


This is what the wet chocolate balls look like right after being dipped and garnished. ©Joyce Hays, Target Health Inc.



15. Later, you can arrange them as you like.


You can have a little bite of heaven, without too much effort. ©Joyce Hays, Target Health Inc.



Can I crow a little about my own recipe? Okay, these petit-fours or little cakes will be like a little bit of heaven in your mouth. You won’t believe how good they are. And, as you can see from the directions, they’re very easy to make.  Enjoy, my friends!


May the Spring of 2017 bring with it, a joyful renewal of much needed hope and peace!

©Joyce Hays, Target Health Inc.



From Our Table to Yours !


Bon Appetit!


April 12, 2017

Washington University in St. Louis

A team of engineers has combined nanoparticles, aerosol science and locusts in new proof-of-concept research that could someday vastly improve drug delivery to the brain, making it as simple as a sniff.


Locust (stock image). Engineers at Washington University in St. Louis used nanoparticles, aerosol technology and locusts in proof of concept research that could someday change the way medicine is delivered to the brain.
Credit: © Irina K. / Fotolia



Delivering life-saving drugs directly to the brain in a safe and effective way is a challenge for medical providers. One key reason: the blood-brain barrier, which protects the brain from tissue-specific drug delivery. Methods such as an injection or a pill aren’t as precise or immediate as doctors might prefer, and ensuring delivery right to the brain often requires invasive, risky techniques.

A team of engineers from Washington University in St. Louis has developed a new nanoparticle generation-delivery method that could someday vastly improve drug delivery to the brain, making it as simple as a sniff.

“This would be a nanoparticle nasal spray, and the delivery system could allow a therapeutic dose of medicine to reach the brain within 30 minutes to one hour,” said Ramesh Raliya, research scientist at the School of Engineering & Applied Science.

“The blood-brain barrier protects the brain from foreign substances in the blood that may injure the brain,” Raliya said. “But when we need to deliver something there, getting through that barrier is difficult and invasive. Our non-invasive technique can deliver drugs via nanoparticles, so there’s less risk and better response times.”

The novel approach is based on aerosol science and engineering principles that allow the generation of monodisperse nanoparticles, which can deposit on upper regions of the nasal cavity via diffusion. Working with Assistant Vice Chancellor Pratim Biswas, chair of the Department of Energy, Environmental & Chemical Engineering and the Lucy & Stanley Lopata Professor, Raliya developed an aerosol consisting of gold nanoparticles of controlled size, shape and surface charge. The nanoparticles were tagged with fluorescent markers, allowing the researchers to track their movement.

Next, Raliya and biomedical engineering postdoctoral fellow Debajit Saha exposed locusts’ antennae to the aerosol, and observed the nanoparticles travel from the antennas up through the olfactory nerves. Due to their tiny size, the nanoparticles passed through the brain-blood barrier, reaching the brain and suffusing it in a matter of minutes.

The team tested the concept in locusts because the blood-brain barriers in the insects and humans have anatomical similarities, and the researchers consider going through the nasal regions to neural pathways as the optimal way to access the brain.

“The shortest and possibly the easiest path to the brain is through your nose,” said Barani Raman, associate professor of biomedical engineering. “Your nose, the olfactory bulb and then olfactory cortex: two relays and you’ve reached the cortex. The same is true for invertebrate olfactory circuitry, although the latter is a relatively simpler system, with supraesophageal ganglion instead of an olfactory bulb and cortex.”

To determine whether or not the foreign nanoparticles disrupted normal brain function, Saha examined the physiological response of olfactory neurons in the locusts before and after the nanoparticle delivery. Several hours after the nanoparticle uptake, no noticeable change in the electrophysiological responses was detected.

“This is only a beginning of a cool set of studies that can be performed to make nanoparticle-based drug delivery approaches more principled,” Raman said.

The next phase of research involves fusing the gold nanoparticles with various medicines, and using ultrasound to target a more precise dose to specific areas of the brain, which would be especially beneficial in brain-tumor cases.

“We want to drug target delivery within the brain using this non-invasive approach,” Raliya said. “In the case of a brain tumor, we hope to use focused ultrasound so we can guide the particles to collect at that particular point.”

Story Source:

Materials provided by Washington University in St. Louis. Note: Content may be edited for style and length.

Journal Reference:

  1. Ramesh Raliya, Debajit Saha, Tandeep S. Chadha, Baranidharan Raman, Pratim Biswas. Non-invasive aerosol delivery and transport of gold nanoparticles to the brain. Scientific Reports, 2017; 7: 44718 DOI: 10.1038/srep44718


Source: Washington University in St. Louis. “Nanoparticle research tested in locusts focuses on new drug-delivery method.” ScienceDaily. ScienceDaily, 12 April 2017. <>.

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