Spinach Salad with Arugula, Clementines and Croutons

It’s fun to be aware of which fruit and veggies are in season and build a recipe around it. Here, the Clementines, at their peak now, are the star attraction. Not only do they add the perfect color, but their sweet tang is the perfect foil for the dressing and slight edginess of the greens. ©Joyce Hays, Target Health Inc.

 

This salad was so-o good, it became my whole dinner with wine and a light dessert. ©Joyce Hays, Target Health Inc.

 

Get all of the ingredients together in one place. Use fresh! Fresh garlic is better than garlic powder. Fresh lemon is better than bottled. Freshly grated parmesan is better than bought and freshly baked croutons taste much better than store bought. I forgot to include the Clementines in this photo. ©Joyce Hays, Target Health Inc.

 

Ingredients 

The Dressing

3 anchovy fillets packed in oil, drained

4 fresh garlic cloves

Pinch Kosher salt

1 large egg yolk (boil egg for 1 minute and not longer)

Zest of 1/2 fresh lemon

2 Tablespoons fresh lemon juice, plus more (to your taste)

3/4 teaspoon Dijon mustard

2 Tablespoons excellent extra virgin olive oil

2 Tablespoons canola oil

6 Tablespoons finely grated FRESH Parmesan

Pinch black pepper

Worchester sauce (one drop)

 

The Croutons

1 cup torn 1“ (bite-size) pieces old bread, with crusts

1 Garlic clove, squeezed

2 teaspoons olive oil

 

The Greens

3 or 4 (packed in tightly) cups of fresh spinach and 3 or 4 cups of (packed in tightly) fresh arugula all leaves separated, washed three times, dried with paper towel. Then leaves torn by hand, put into a bowl and set aside. Both of these green veggies are grown in sandy soil. This is why you really need to wash all the leaves three times, draining each time. Even though the packaging makes the leaves look clean, there’s always a certain amount of sand and/or grit left on the leaves, that’s not visible. It ruins a good salad to feel your teeth crunch down on grains of sand or grit. Also, you have no idea who handled the leaves before or during packaging. It means 5 extra minutes of work, to do this washing routine, but it’s worth the time.

 

Even fresh looking greens need to be washed three times and drained in between the washing. Last, dry the leaves with paper towel. ©Joyce Hays, Target Health Inc.

  

Clementines

 

1, 2 or 3, depending on your taste

 

They’re in season now and couldn’t be more sweet and juicy. Simply peel and separate the segments. Use whole segments or cut them in half. Pick out any seeds that’re sticking out, but don’t bother digging into a segment to get them out, unless you feel like doing it.

 

Directions

The Croutons, certainly, can be made the day before and so can the dressing. Otherwise, make croutons first, before you make the dressing. Can you buy packaged croutons? Of course, but try to make them yourself. The flavor is so much better. If you’re going to make a really great salad, you might as well make great tasting croutons. There is simply no comparison! Once you taste the richness of your own croutons, you’ll never buy them again. They’re not a peripheral ingredient, they make the salad better. That’s why they’re in the recipe.

 

1. Preheat oven to 375 degrees.

2. In a medium bowl, add the 2 teaspoons olive oil and the squeezed juice of one fresh garlic clove. Stir

3. Tear or cut any left-over bread, you have, into (1 inch) bite size pieces, enough for 1 cup (press the bread down a bit, in the measuring cup). Then put the pieces of bread, into the bowl with oil/garlic. My favorite bread for croutons is day old (or older) sour dough bread.

4. Now, toss the bread pieces or cubes and be sure that the bread cubes are all covered (as much as possible) with the oil mixture. Let them sit for a while to absorb the oil, like 30 to 60 minutes. Stir them around every once in a while

5. Arrange croutons on a baking sheet or large pan and bake, tossing occasionally, until golden, 10-15 minutes. Watch them carefully. Just a little too long in the oven, and they will burn and won’t be useable for the salad. When golden, remove from oven and set aside to cool.

 

Croutons are about to go into the oven. You can see that some pieces have more oil than others. Doesn’t matter. Once added to the salad, dressing will rub onto the croutons and they’ll be delicious. ©Joyce Hays, Target Health Inc.

 

Out of the oven, crisp, crunchy and delicious; ready to be added to the salad. These are a hundred times better than store-bought. ©Joyce Hays, Target Health Inc.

 

The Dressing

1. Use a medium bowl to make the dressing in.

2. Boil one large egg for one minute and remove from heat after 1 minute. Immediately run the egg under cold water. Then carefully crack it open, so as not to break the yolk. You have to separate the yolk from the egg white and use only the yolk in this recipe. Separate and put the yolk into a small container, ready to use in the dressing. This is a precaution worth taking, to prevent salmonella. Never use a completely raw egg.

 

You’ve got to boil the one egg (for the dressing), for 1 minute and not longer. This is a short cautionary step, so as not to get salmonella. ©Joyce Hays, Target Health Inc.

 

Freshly grated parmesan means doing it yourself. There’s no substitute. Buying a container that reads “freshly grated“ simply is NOT. After a while, you’ll see, there’s something satisfying about doing it yourself. However, if you’re working and raising kids, everyone understands that, so do what you have to do. If kids are old enough, let them share the various steps of a recipe. ©Joyce Hays, Target Health Inc.

 

3. In bottom of salad serving bowl put the garlic and the anchovies. With a fork, mash these two ingredients into a paste

4. Next, with a small whisk, add the egg yolk and whisk it into the garlic/anchovy paste; or continue to use the fork.

5. Now, add the lemon zest, 2 Tablespoons of fresh lemon juice and whisk; then add the mustard and 1 drop of Worchester sauce, whisk again

 

This type of lemon squeezer catches the seeds while letting the juice flow through. ©Joyce Hays, Target Health Inc.

 

6. Next, add the extra virgin olive oil and whisk it into the dressing.

7. Add the canola oil drop by drop, while you whisk it into the dressing.

8. Finally, add the freshly grated parmesan and black pepper (to your taste). Taste to see if the dressing needs more of anything (to your taste). With the anchovies, you may decide not to use any salt. You might want more lemon juice. This is the time to taste and decide. I don’t think you need salt, since the anchovies are salty enough.

9. Whisk the dressing so it’s thick and glossy.

10. When you’re ready to serve, add the greens to the dressing in bottom of salad bowl and toss many times to get each leaf covered with the delicious dressing.

11. Finally, add the croutons and the Clementine segments and toss a few more times, to combine everything.

 

Enjoy!

 

Such a delicious way to get your daily dose of magnesium. ©Joyce Hays, Target Health Inc.

 

Experimenting recently, with Chateauneuf du Pape. So far, not living up to expectations, but will keep you posted as we move forward into this new taste adventure. ©Joyce Hays, Target Health Inc.

 

Have a great week everyone!

 

From Our Table to Yours

Bon Appetit!

 

Date:
December 8, 2017

Source:
University of New South Wales

Summary:
As far our brain is concerned, talking to ourselves in our heads may be fundamentally the same as speaking our thoughts out loud, new research shows. The findings may have important implications for understanding why people with mental illnesses such as schizophrenia hear voices.

 

We spend a lot of time listening to our own inner speech. But to what extent does the brain distinguish between inner speech and the sounds we produce when we speak out loud?
Credit: © adimas / Fotolia

 

 

As far our brain is concerned, talking to ourselves in our heads may be fundamentally the same as speaking our thoughts out loud, new research shows. The findings may have important implications for understanding why people with mental illnesses such as schizophrenia hear voices.

UNSW Sydney scientist and study first author Associate Professor Thomas Whitford says it has long been thought that these auditory-verbal hallucinations arise from abnormalities in inner speech — our silent internal dialogue.

“This study provides the tools for investigating this once untestable assumption,” says Associate Professor Whitford, of the UNSW School of Psychology.

Previous research suggests that when we prepare to speak out loud, our brain creates a copy of the instructions that are sent to our lips, mouth and vocal cords. This copy is known as an efference-copy.

It is sent to the region of the brain that processes sound to predict what sound it is about to hear. This allows the brain to discriminate between the predictable sounds that we have produced ourselves, and the less predictable sounds that are produced by other people.

“The efference-copy dampens the brain’s response to self-generated vocalisations, giving less mental resources to these sounds, because they are so predictable,” says Associate Professor Whitford.

“This is why we can’t tickle ourselves. When I rub the sole of my foot, my brain predicts the sensation I will feel and doesn’t respond strongly to it. But if someone else rubs my sole unexpectedly, the exact same sensation will be unpredicted. The brain’s response will be much larger and creates a ticklish feeling.”

The study, published in the journal eLife, set out to determine whether inner speech — an internal mental process — elicits a similar efference-copy as the one associated with the production of spoken words.

The research team developed an objective method for measuring the purely mental action of inner speech. Specifically, their study in 42 healthy participants assessed the degree to which imagined sounds interfered with the brain activity elicited by actual sounds, using electroencephalography (EEG).

The researchers found that, just as for vocalized speech, simply imagining making a sound reduced the brain activity that occurred when people simultaneously heard that sound. People’s thoughts were enough to change the way their brain perceived sounds. In effect, when people imagined sounds, those sounds seemed quieter.

“By providing a way to directly and precisely measure the effect of inner speech on the brain, this research opens the door to understanding how inner speech might be different in people with psychotic illnesses such as schizophrenia,” says Associate Professor Whitford.

“We all hear voices in our heads. Perhaps the problem arises when our brain is unable to tell that we are the ones producing them.”

Story Source:

Materials provided by University of New South WalesNote: Content may be edited for style and length.


Journal Reference:

  1. Thomas J Whitford, Bradley N Jack, Daniel Pearson, Oren Griffiths, David Luque, Anthony WF Harris, Kevin M Spencer, Mike E Le Pelley. Neurophysiological evidence of efference copies to inner speecheLife, 2017; 6 DOI: 10.7554/eLife.28197

 

Source: University of New South Wales. “Talking to ourselves and voices in our heads.” ScienceDaily. ScienceDaily, 8 December 2017. <www.sciencedaily.com/releases/2017/12/171208143043.htm>.

Date:
December 6, 2017

Source:
Frontiers

Summary:
Newly emerging trends in data suggests humans may have reached their maximum limits for height, lifespan and physical performance. These biological limitations may be affected by anthropogenic impacts on the environment – including climate change – which could have a deleterious effect on these limits. This review is the first of its kind spanning 120 years worth of historical information, while considering the effects of both genetic and environmental parameters.

 

There appears to be a plateau in the maximum biological limits for humans’ height, age and physical abilities, and we seem to have reached it.
Credit: © ChiccoDodiFC / Fotolia

 

 

Humans may have reached their maximum limits for height, lifespan and physical performance. A recent review suggests humans have biological limitations, and that anthropogenic impacts on the environment — including climate change — could have a deleterious effect on these limits. Published in Frontiers in Physiology, this review is the first of its kind spanning 120 years worth of historical information, while considering the effects of both genetic and environmental parameters.

Despite stories that with each generation we will live longer and longer, this review suggests there may be a maximum threshold to our biological limits that we cannot exceed.

A transdisciplinary research team from across France studied trends emerging from historical records, concluding that there appears to be a plateau in the maximum biological limits for humans’ height, age and physical abilities.

“These traits no longer increase, despite further continuous nutritional, medical, and scientific progress. This suggests that modern societies have allowed our species to reach its limits. We are the first generation to become aware of this” explains Professor Jean-François Toussaint from Paris Descartes University, France.

Rather than continually improving, we will see a shift in the proportion of the population reaching the previously recorded maximum limits. Examples of the effects of these plateaus will be evidenced with increasingly less sport records being broken and more people reaching but not exceeding the present highest life expectancy.

However, when researchers considered how environmental and genetic limitations combined may affect the ability for us to reach these upper limits, our effect on the environment was found to play a key role.

“This will be one of the biggest challenges of this century as the added pressure from anthropogenic activities will be responsible for damaging effects on human health and the environment.” Prof. Toussaint predicts. “The current declines in human capacities we can see today are a sign that environmental changes, including climate, are already contributing to the increasing constraints we now have to consider.”

“Observing decreasing tendencies may provide an early signal that something has changed but not for the better. Human height has decreased in the last decade in some African countries; this suggests some societies are no longer able to provide sufficient nutrition for each of their children and maintain the health of their younger inhabitants,” Prof. Toussaint explains.

To avoid us being the cause of our own decline, the researchers hope their findings will encourage policymakers to focus on strategies for increasing quality of life and maximize the proportion of the population that can reach these maximum biological limits.

“Now that we know the limits of the human species, this can act as a clear goal for nations to ensure that human capacities reach their highest possible values for most of the population. With escalating environmental constraints, this may cost increasingly more energy and investment in order to balance the rising ecosystem pressures. However, if successful, we then should observe an incremental rise in mean values of height, lifespan and most human biomarkers.” Prof. Toussaint warns however, “The utmost challenge is now to maintain these indices at high levels.”

Story Source:

Materials provided by FrontiersNote: Content may be edited for style and length.


Journal Reference:

  1. Adrien Marck, Juliana Antero, Geoffroy Berthelot, Guillaume Saulière, Jean-Marc Jancovici, Valérie Masson-Delmotte, Gilles Boeuf, Michael Spedding, Éric Le Bourg, Jean-François Toussaint. Are We Reaching the Limits of Homo sapiens?Frontiers in Physiology, 2017; 8 DOI: 10.3389/fphys.2017.00812

 

Source: Frontiers. “Humans at maximum limits for height, lifespan and physical performance, study suggests.” ScienceDaily. ScienceDaily, 6 December 2017. <www.sciencedaily.com/releases/2017/12/171206122502.htm>.

 

Mice with genes that activate a protein pathway have leaner fat cells

Date:
December 5, 2017

Source:
Washington University School of Medicine

Summary:
Researchers activated the Hedgehog protein pathway in the fat cells of mice. After eight weeks of eating a high-fat diet, mice that had been engineered with genes to activate the pathway didn’t gain weight, but control animals whose Hedgehog pathways were not activated became obese.

 

Washington University researchers activated the Hedgehog protein pathway in the fat cells of mice. After eight weeks of eating a high-fat diet, mice that had been engineered with genes to activate the pathway didn’t gain weight (left), but control animals whose Hedgehog pathways were not activated became obese (right).
Credit: Washington University School of Medicine

Researchers at Washington University School of Medicine in St. Louis have identified a way to prevent fat cells from growing larger, a process that leads to weight gain and obesity. By activating a pathway in fat cells in mice, the researchers found they could feed the animals a high-fat diet without making them obese.

The study is published online Dec. 5 in the journal eLife.

“This could lead us to a new therapeutic target for treating obesity,” said senior investigator Fanxin Long, PhD, a professor of orthopedic surgery. “What’s particularly important is that the animals in our study ate a high-fat diet but didn’t gain weight, and in people, too much fat in the diet is a common cause of obesity.”

Long’s research focused on the so-called Hedgehog protein pathway that is active in many tissues in the body. His team engineered mice with genes that activated the Hedgehog pathway in fat cells when those animals ate a high-fat diet.

After eight weeks of eating the high-fat diet, control animals whose Hedgehog pathways had not been activated became obese. But the mice that had been engineered with genes to activate the pathway didn’t gain any more weight than did control animals that consumed normal diets.

The Hedgehog pathway prevented obesity by inhibiting the size of the fat cells, Long said.

“Fat gain is due mainly to increased fat cell size,” he explained. “Each fat cell grows bigger so that it can hold larger fat droplets. We gain weight mainly because fat cells get bigger, as opposed to having more fat cells.”

By stimulating Hedgehog and related proteins in fat cells, Long’s team kept the animals’ fat cells from collecting and storing fat droplets.

“More importantly, when we did metabolic studies, we found that the animals with the active Hedgehog pathway not only were leaner, they also had lower blood-glucose levels and were more sensitive to insulin,” he said.

Translating the findings to humans could be tricky, he said, and any drugs that activate the Hedgehog pathway would need to be carefully targeted to avoid potential side effects. Certain cancers have been linked to too much Hedgehog activity, for example. But because the pathway is believed to work in similar ways in humans and mice, it might be possible to target the pathway to the fat tissue as a treatment for obesity, Long said.

“If we can come up with strategies to carefully target fat cells, then I think activating this pathway could be effective in the fight against obesity,” he said.

More than one-third of the adult population in the United States is obese, and the estimated annual medical costs for obesity exceed $147 billion. People with obesity have an increased risk for stroke, heart attack, diabetes and cancer.

Story Source:

Materials provided by Washington University School of MedicineNote: Content may be edited for style and length.


Journal Reference:

  1. Yu Shi, Fanxin Long. Hedgehog signaling via Gli2 prevents obesity induced by high-fat diet in adult miceeLife, 2017; 6 DOI: 10.7554/eLife.31649

 

Source: Washington University School of Medicine. “Obesity prevented in mice fed high-fat diet: Mice with genes that activate a protein pathway have leaner fat cells.” ScienceDaily. ScienceDaily, 5 December 2017. <www.sciencedaily.com/releases/2017/12/171205115946.htm>.

Date:
December 4, 2017

Source:
University of Texas at Austin

Summary:
Scientists have long pondered how rocky bodies in the solar system — including our own Earth — got their metal cores. According to new research, evidence points to the downwards percolation of molten metal toward the center of the planet through tiny channels between grains of rock.

 

New research from The University of Texas at Austin adds evidence to a theory that claims the metallic cores of rocky planets like Earth were formed when molten metal trapped between grains of silicate rock percolated to the center of the planet during its early formation.
Credit: UT Austin

 

 

Scientists have long pondered how rocky bodies in the solar system — including our own Earth — got their metal cores. According to research conducted by The University of Texas at Austin, evidence points to the downwards percolation of molten metal toward the center of the planet through tiny channels between grains of rock.

The finding calls into question the interpretation of prior experiments and simulations that sought to understand how metals behave under intense heat and pressure when planets are forming. Past results suggested that large portions of molten metals stayed trapped in isolated pores between the grains. In contrast, the new research suggests that once those isolated pores grow large enough to connect, the molten metal starts to flow, and most of it is able to percolate along grain boundaries. This process would let metal trickle down through the mantle, accumulate in the center, and form a metal core, like the iron core at the heart of our home planet.

“What we’re saying is that once the melt network becomes connected, it stays connected until almost all of the metal is in the core,” said co-author Marc Hesse, an associate professor in the UT Jackson School of Geosciences Department of Geological Sciences, and a member of UT’s Institute for Computational Engineering and Sciences.

The research was published on Dec. 4 in the Proceedings of the National Academy of Sciences. The work was the doctoral thesis of Soheil Ghanbarzadeh, who earned his Ph.D. while a student in the UT Department of Petroleum and Geosystems Engineering (now the Hildebrand Department of Petroleum and Geosystems Engineering). He currently works as a reservoir engineer with BP America. Soheil was jointly advised by Hesse and Maša Prodanovic, an associate professor in the Hildebrand Department and a co-author.

Planets and planetesimals (small planets and large asteroids) are formed primarily from silicate rocks and metal. Part of the planet formation process involves the initial mass of material separating into a metallic core and a silicate shell made up of the mantle and the crust. For the percolation theory of core formation to work, the vast majority of metal in the planetary body must make its way to the center.

In this study, Ghanbarzadeh developed a computer model to simulate the distribution of molten iron between rock grains as porosity, or melt fraction, increased or decreased. The simulations were perfomed at the Texas Advanced Computing Center. Researchers found that once the metal starts to flow, it can continue flowing even as the melt fraction decreases significantly. This is in contrast to previous simulations that found that once the metal starts flowing, it only takes a small dip in the volume of melt for percolation to stop.

“People have assumed that you disconnect at the same melt fraction at which you initially connected…and it would leave significant amounts of the metal behind,” Hesse said. “What we found is that when the metallic melt connects and when it disconnects is not necessarily the same.”

According to the computer model, only 1 to 2 percent of the initial metal would be trapped in the silicate mantle when percolation stops, which is consistent with the amount of metal in the Earth’s mantle.

The researchers point to the arrangement of the rock grains to explain the differences in how well-connected the spaces between the grains are. Previous work used a geometric pattern of regular, identical grains, while this work relied on simulations using an irregular grain geometry, which is thought to more closely mirror real-life conditions. The geometry was generated using data from a polycrystalline titanium sample that was scanned using X-ray microtomography.

“The numerical model Soheil developed in his Ph.D. thesis allowed for finding three-dimensional melt networks of any geometrical complexity for the first time,” said Prodanovic. “Having a three-dimensional model is key in understanding and quantifying how melt trapping works.”

The effort paid off because researchers found that the geometry has a strong effect on melt connectivity. In the irregular grains, the melt channels vary in width, and the larges ones remain connected even as most of the metal drains away.

“What we did differently in here was to add the element of curiosity to see what happens when you drain the melt from the porous, ductile rock,” said Ghanbarzadeh.

The researchers also compared their results to a metallic melt network preserved in an anchondrite meteorite, a type of meteorite that came from a planetary body that differentiated into discernable layers. X-ray images of the meteorite taken in the Jackson School’s High-Resolution X-Ray CT Facility revealed a metal distribution that is comparable to the computed melt networks. Prodanovic said that this comparison shows that their simulation capture the features observed in the meteorite.

The study was funded by the Statoil Fellows Program at UT Austin and the National Science Foundation.

Story Source:

Materials provided by University of Texas at AustinNote: Content may be edited for style and length.


Journal Reference:

  1. Soheil Ghanbarzadeh, Marc A. Hesse, Maša Prodanović. Percolative core formation in planetesimals enabled by hysteresis in metal connectivityProceedings of the National Academy of Sciences, 2017; 201707580 DOI: 10.1073/pnas.1707580114

 

Source: University of Texas at Austin. “Trickle-down is the solution (to the planetary core formation problem).” ScienceDaily. ScienceDaily, 4 December 2017. <www.sciencedaily.com/releases/2017/12/171204162351.htm>.

Holiday in New York City

 

December begins the holiday season in NY for Target Health with red poinsettias everywhere in our offices on Madison Avenue. Holiday wishes to all.

Holiday time the 23rd and 24th floors. ©Target Health Inc.

 

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

 

QUIZ

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Prion Protein Found in Skin of CJD Patients

Dark green areas are countries that have confirmed human cases of variant Creutzfeldt-Jakob disease and light green are countries that have bovine spongiform encephalopathy cases. Graphic credit: CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=1052077

Funding for this project was provided by the NIH/National Institute of Allergy and Infectious Diseases

 

Transmissible spongiform encephalopathy diseases are caused by prions. Prions are proteins that occur normally in neurons of the central nervous system (CNS). These proteins are thought to affect signaling processes, damaging neurons and resulting in degeneration that causes the spongiform appearance in the affected 1) ___. The CJD prion is dangerous because it promotes refolding of native prion protein into the diseased state. The number of misfolded protein molecules will increase exponentially and the process leads to a large quantity of insoluble protein in affected cells. This mass of misfolded proteins disrupts neuronal cell function and causes cell 2) ___. Mutations in the gene for the prion protein can cause a misfolding of the dominantly alpha helical regions into beta pleated sheets. This change in conformation disables the ability of the protein to undergo digestion. Once the prion is transmitted, the defective proteins invade the brain and induce other prion protein molecules to misfold in a self-sustaining feedback loop. These neurodegenerative diseases are commonly called prion diseases.

 

People can also develop CJD because they carry a mutation of the gene that codes for the prion protein (PRNP). This occurs in only 5-10% of all CJD cases. In sporadic cases the misfolding of the prion 3) ___ probably occurs as a natural, spontaneous process. An EU study determined that “87% of cases were sporadic, 8% genetic, 5% iatrogenic and less than 1% variant.“

 

National Institutes of Health (NIH) scientists and collaborators at Case Western Reserve University School of Medicine have detected abnormal prion protein in the skin of nearly two dozen people who died from Creutzfeldt-Jakob disease (CJD). The scientists also exposed a dozen healthy mice to skin extracts from two of the CJD patients, and all developed prion disease. The study results, published in Science Translational Medicine, raise questions about the possible transmissibility of prion diseases via medical procedures involving skin, and whether 4) ___ samples might be used to detect prion disease. Researchers from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) were co-leaders of the study, which included multiple collaborating groups. They stress that the prion-seeding potential found in skin tissue is significantly less than what they have found in studies using brain tissue.

 

CJD is an incurable — and ultimately fatal — transmissible, neurodegenerative disorder in the family of prion diseases. Prion diseases originate when normally harmless prion protein molecules become abnormal and gather in clusters and filaments in the human body and brain. The reasons for this process are not fully understood. The accumulation of these clusters has been associated with tissue damage that leaves sponge-like holes in the brain. Human prion diseases include fatal insomnia; kuru; Gerstmann-Straussler-Scheinker syndrome; and variant, familial and sporadic CJD. Sporadic CJD is the most common human prion disease, affecting about one in one million people annually worldwide. Other 5) ___ diseases include scrapie in sheep; chronic wasting disease in deer, elk and moose; and bovine spongiform encephalopathy, or mad cow disease, in cattle. Most people associate prion diseases with the brain, although scientists have found abnormal infectious prion protein in other organs, including the spleen, kidney, lungs and liver. Sporadic CJD is known to be transmissible by invasive medical procedures involving the central 6) ___system and cornea, but transmission via skin had not been a common concern.

 

Using a test for prion diseases known as Real-Time Quaking-Induced Conversion (RT-QuIC), scientists analyzed skin tissue from 38 patients — 23 who had died from CJD, and 15 who died of other causes. They also collected brain tissue from the 23 CJD patients and from seven individuals who died of other causes. RT-QuIC correctly detected abnormal prion protein in each CJD patient sample tested and in none of the non-CJD group. The scientists noted that in the CJD group, the “seeding potential“ for normal prion protein to convert to abnormal was 1,000 to 100,000 times lower in skin than brain 7) ___. The scientists then exposed humanized laboratory mice to either brain or skin extracts from two of the CJD patients. All 12 mice inoculated with brain tissue developed prion disease, as did all 12 inoculated with skin extracts, though disease in the skin group took about twice as long — roughly 400 days — to develop. The group also reported that brain degeneration in both groups of infected 8) ___ was similar. The study authors say the results should generate discussion about potential surgical instrument contamination and risk associated with procedures involving CJD patients. “Perspective is important when interpreting these outcomes,“ said Byron Caughey, Ph.D., a senior investigator at NIAID’s Rocky Mountain Laboratories (RML) who helped oversee the study. “This study used humanized mice with tissue extracts directly inoculated into the brain, so the system was highly primed for infection. There is no 9) ___ that transmission can occur in real-world situations via casual skin contact. However, the results raise transmission questions that warrant further study.“ The study also raises the possibility of using RT-QuIC with skin tissue samples as a diagnostic test for human and animal prion diseases. The test is widely used with samples of brain and spinal-fluid for the diagnosis of CJD, but such samples are not always available. “Our objective has always been to facilitate RT-QuIC testing using the most broadly available and least-invasive sample possible, whether that is blood, skin, nasal brushings, or other samples,“ Dr. Caughey said. His research group has developed RT-QuIC over the past decade at RML, where he also has trained many international colleagues to use and advance the 10) ___. Dr. Caughey’s group is continuing its development of RT-QuIC applications, including further studies of when and where the pathological prion protein appears in skin, and how to effectively inactivate its infectious forms. Sources: NIH/National Institute of Allergy and Infectious Diseases; ScienceDaily; Wikipedia; Prion seeding activity and infectivity in skin samples from patients with sporadic Creutzfeldt-Jakob disease. Science Translational Medicine, 2017; 9 (417): eaam7785 DOI: 10.1126/scitranslmed.aam7785

 

ANSWERS: 1) brain; 2) death; 3) protein; 4) skin; 5) prion; 6) nervous; 7) tissue; 8) mice; 9) evidence; 10) test

 

Hans Gerhard Creutzfeldt MD

Hans Gerhard Creutzfeldt (June 2, 1885 – December 30, 1964) was a German neuropathologist, who first described the Creutzfeldt-Jakob disease. He was born in Harburg upon Elbe and died in Munich.

Photo credit: Unknown – http://www.sammlungen.hu-berlin.de/dokumente/11727/, Public Domain, https://commons.wikimedia.org/w/index.php?curid=4008658

 

 

Hans Gerhard Creutzfeldt was born into a medical family in Harburg, which was incorporated into Hamburg in 1937. In 1903, at the age of 18, Creutzfeldt was drafted into the German army and spent his service stationed in Kiel. Afterwards, he attended the School of Medicine of the Universities of University of Jena and University of Rostock, receiving his doctorate at the latter in 1909. Part of his practical training was undertaken at St. Georg – Hospital in Hamburg. After qualification he sought adventure as a ship’s surgeon, voyaging the Pacific Ocean, taking the opportunity to study local crafts, linguistics, and tropical plants. After returning to Germany, Creutzfeldt worked at the Neurological Institute in Frankfurt am Main, at the psychiatric-neurological clinics in Breslau, Kiel and Berlin, and at the Deutsche Forschungsanstalt fur Psychiatrie in Munich. Creutzfeldt was habilitated at Kiel in 1920, and in 1925 became Extraordinarius of psychiatry and neurology. In 1938 he was appointed professor and director of the university psychiatric and neurological division in Kiel. Later, Creutzfeldt helped to recognize a neurodegenerative disease, with Alfons Maria Jakob, now known as Creutzfeldt-Jakob disease, in which the brain tissue develops holes and takes on a sponge-like texture. It is now known that this disease is due to a type of infectious protein called a prion. Prions are misfolded proteins which replicate by converting their properly folded counterparts.

 

In the Third Reich, Creutzfeldt became a Patron Member of Heinrich Himmler’s SS. However, when Creutzfeldt was 54 years old and WW2 broke out, he was unmoved by the Nazi regime and was able to save some people from death in concentration camps. He also managed to rescue almost all of his patients from being murdered under the Nazi Action T4 euthanasia program, an unusual event since most mental patients identified by T4 personnel were gassed or poisoned at separate euthanasia clinics such as Hadamar Euthanasia Centre. During the war, bombing raids destroyed his home and clinic. After the war he was director of the University of Kiel for six months, before being dismissed by the British occupation forces. His efforts to rebuild the university caused a series of conflicts with the British because he wanted to allow more former army officers to study there. In 1953 he moved on to Munich to work on scientific research commissioned by the Max Planck Society.

 

Creutzfeldt was married to Clara Sombart, a daughter of Werner Sombart. They had five children, among them Otto Detlev Creutzfeldt and Werner Creutzfeldt (1924-2006), a renowned German Internist. Hans Gerhard Creutzfeldt died in 1964 in Munich.

 

As mentioned above, Creutzfeldt-Jakob disease, is a subacute spongiform encephalopathy caused from prions involving the cerebral cortex, the basal ganglia and the spinal cord. Some of the clinical findings described in the Creutzfeldt and Jakob first papers do not match current criteria for Creutzfeldt-Jakob disease. It has been speculated that at least two of the patients in initial studies were suffering from a different ailment. A study published in 1997 counted more than 100 cases worldwide of transmissible CJD and new cases continued to appear at the time. The first report of suspected iatrogenic CJD was published in 1974. Animal experiments showed that corneas of infected animals could transmit CJD, and the causative agent spreads along visual pathways. A second case of CJD associated with a corneal transplant was reported without details. In 1977, CJD transmission caused by silver electrodes previously used in the brain of a person with CJD was first reported. Transmission occurred despite decontamination of the electrodes with ethanol and formaldehyde. Retrospective studies identified four other cases likely of similar cause. The rate of transmission from a single contaminated instrument is unknown, although it is not 100%. In some cases, the exposure occurred weeks after the instruments were used on a person with CJD.

 

A review article published in 1979 indicated that 25 dura mater cases had occurred by that date in Australia, Canada, Germany, Italy, Japan, New Zealand, Spain, the United Kingdom, and the United States.

By 1985, a series of case reports in the United States showed that when injected, cadaver-extracted pituitary human growth hormone could transmit CJD to humans. In 1992, it was recognized that human gonadotropin administered by injection could also transmit CJD from person to person. In 2004, a report published by Edinburgh doctors in the Lancet medical journal demonstrated that vCJD was transmitted by blood transfusion.

 

Stanley B. Prusiner of the University of California, San Francisco (UCSF) was awarded the Nobel Prize in physiology or medicine in 1997 “for his discovery of Prions – a new biological principle of infection“. However, Yale University neuropathologist Laura Manuelidis has challenged the prion protein (PrP) explanation for the disease. In January 2007, she and her colleagues reported that they had found a virus-like particle in naturally and experimentally infected animals. “The high infectivity of comparable, isolated virus-like particles that show no intrinsic PrP by antibody labeling, combined with their loss of infectivity when nucleic acid-protein complexes are disrupted, make it likely that these 25-nm particles are the causal TSE virions.“ Four Australians had been reported with CJD following transfusion as of 1997. There have been ten cases of healthcare-acquired CJD in Australia. They consist of five deaths following treatment with pituitary extract hormone for either infertility or short stature, with no further cases since 1991. The five other deaths were caused by dura grafting during brain surgery, where the covering of the brain was repaired. There have been no other known healthcare-acquired CJD deaths in Australia. A case was reported in 1989 in a 25-year-old man from New Zealand, who also received dura mater transplant. Five New Zealanders have been confirmed to have died of the sporadic form of Creutzfeldt-Jakob disease (CJD) in 2012.

 

Researchers believe one in 2,000 people in the UK is a carrier of the disease linked to eating contaminated beef (vCJD). The survey provides the most robust prevalence measure to date – and identifies abnormal prion protein across a wider age group than found previously and in all genotypes, indicating “infection“ may be relatively common. This new study examined over 32,000 anonymous appendix samples. Of these, 16 samples were positive for abnormal prion protein, indicating an overall prevalence of 493 per million population, or one in 2,000 people are likely to be carriers. No difference was seen in different birth cohorts (1941-60 and 1961-85), in both genders, and there was no apparent difference in abnormal prion prevalence in three broad geographical areas. Genetic testing of the 16 positive samples revealed a higher proportion of valine homozygous (VV) genotype on the codon 129 of the gene encoding the prion protein (PRNP) compared with the general UK population. This also differs from the 177 patients with vCJD, all of whom to date have been methionine homozygous (MM) genotype. The concern is that individuals with this VV genotype may be susceptible to developing the condition over longer incubation periods.

 

In 1988, there was a confirmed death from CJD of a person from Manchester, New Hampshire in the United States. Massachusetts General Hospital believed the patient acquired the disease from a surgical instrument at a podiatrist’s office. In September 2013, another patient in Manchester, New Hampshire was posthumously determined to have died of the disease. The patient had undergone brain surgery at Catholic Medical Center three months before his death, and a surgical probe used in the procedure was subsequently reused in other operations. Public health officials identified thirteen patients at three hospitals who may have been exposed to the disease through the contaminated probe, but said the risk of anyone’s contracting CJD is “extremely low.“ In January 2015, the former speaker of the Utah House of Representatives, Rebecca D. Lockhart, died of the disease within a few weeks of diagnosis. John Carroll, former editor of The Baltimore Sun and Los Angeles Times, died of CJD in Kentucky in June 2015, after having been diagnosed in January. American actress Barbara Tarbuck (General Hospital, American Horror Story) died of the disease on December 26, 2016.

 

An experimental treatment was given to a Northern Irish teenager, Jonathan Simms, beginning in January 2003. The medication, called pentosan polysulphate (PPS) and used to treat interstitial cystitis, is infused into the patient’s lateral ventricle within the brain. PPS does not seem to stop the disease from progressing, and both brain function and tissue continue to be lost. However, the treatment is alleged to slow the progression of the otherwise untreatable disease, and may have contributed to the longer than expected survival of the seven patients studied. Simms died in 2011. The CJD Therapy Advisory Group to the UK Health Departments advises that data are not sufficient to support claims that pentosan polysulphate is an effective treatment and suggests that further research in animal models is appropriate. A 2007 review of the treatment of 26 patients with PPS finds no proof of efficacy because of the lack of accepted objective criteria. Scientists have investigated using RNA interference to slow the progression of scrapie in mice. The RNA blocks production of the protein that the CJD process transforms into prions. This research is unlikely to lead to a human therapy for many years. Both amphotericin B and doxorubicin have been investigated as potentially effective against CJD, but as yet there is no strong evidence that either drug is effective in stopping the disease. Further study has been taken with other medical drugs, but none are effective. However, anticonvulsants and anxiolytic agents, such as valproate or a benzodiazepine, may be administered to relieve associated symptoms.

 

Scientists from the University of California, San Francisco are currently running a treatment trial for sporadic CJD using quinacrine, a medicine originally created for malaria. Pilot studies showed quinacrine permanently cleared abnormal prion proteins from cell cultures, but results have not yet been published on their clinical study. The efficacy of quinacrine was also assessed in a rigorous clinical trial in the UK and the results were published in Lancet Neurology, and concluded that quinacrine had no measurable effect on the clinical course of CJD. In a 2013 paper published in the Proceedings of the National Academy of Sciences, scientists from The Scripps Research Institute reported that Astemizole, a medication approved for human use, has been found to have anti-prion activity and may lead to a treatment for Creutzfeldt-Jakob disease.

 

Study of WWII Evacuees Suggests Mental Illness May Be Passed to Offspring

 

From 1941 to 1945, roughly 49,000 Finish children were evacuated from their homes to protect them from bombings, malnutrition and other hazards during the country’s wars with the Soviet Union. The children, many of them only preschoolers, were placed with foster families in Sweden. In addition to separation from their families, the children faced the stresses of adapting to their foster families, and in many cases, learning a new language. Upon their return, many children experienced the additional stress of readjusting to Finnish society. During the same time, thousands of Finnish families chose not to evacuate all their children and often kept some at home, but little information exists on the rationale for their decisions.

 

According to an article published in JAMA Psychiatry (29 November 2017), a study of the adults whose parents evacuated Finland as children during World War II, suggests that mental illness associated with early childhood adversity may be passed from generation to generation,. The study was conducted by researchers at the National Institutes of Health, Uppsala University in Sweden, and Helsinki University in Finland. Results showed that daughters of female evacuees had the same high risk for mental health disorders as their mothers, even though they did not experience the same adversity. However, the study could not determine why the higher risk for mental illness persisted across generations. Possible explanations include changes in the evacuees’ parenting behavior stemming from their childhood experience or epigenetic changes — chemical alterations in gene expression, without any changes to underlying DNA.

 

For the study, the authors compared the risk of being hospitalized for a psychiatric (mental health) disorder among offspring of the evacuees to the risks of psychiatric hospitalization among the offspring of the siblings who remained with their parents. Studying the two groups — cousins to each other — allowed the authors to compensate for family-based factors that can contribute to mental health problems and to focus instead on the evacuees’ wartime experience.

 

In a previous study, the authors found that women evacuated as children were more than twice as likely to be hospitalized for a psychiatric disorder than their female siblings who remained at home. For the current study, the authors linked records from this generation — more than 46,000 siblings born between 1933 and 1944 — to those of their offspring, more than 93,000 individuals born after 1950. Of these, nearly 3,000 were offspring of parents who had been evacuated to Sweden as children, and more than 90,000 were offspring of parents who remained in Finland during the war. The authors found that female evacuees and their daughters were at the greatest risk for being hospitalized for mood disorders, such as depression and bipolar disorder. In fact, the evacuees’ daughters had more than four times the risk of hospitalization for a mood disorder, compared to the daughters of mothers who stayed home — regardless of whether their mothers were hospitalized for a mood disorder. The authors did not find any increase in psychiatric hospitalizations for the sons or daughters of males who had been evacuated as children. The study could not determine why the daughters of female evacuees had a higher risk of mental illness. One possibility is that the stresses of the evacuees’ experience affected their psychological development in ways that influenced their parenting style. Another possibility is that the evacuee experience resulted in epigenetic changes. For example, the authors cited an earlier finding that Holocaust survivors have higher levels of compounds known as methyl groups bound to the gene FKBP5 and have passed this change on to their children. This higher level of methyl groups appears to alter the production of cortisol, a hormone that regulates the stress response.

 

The authors concluded that future studies are needed to understand how the experience of war affects the mental health of parents and their offspring and to develop interventions to help families affected by armed conflict.

 

Hibernating Ground Squirrels Provide Clues to New Stroke Treatments

 

An ischemic stroke occurs when a clot cuts off blood flow to part of the brain, depriving those cells of oxygen and nutrients like the blood sugar glucose that they need to survive. Nearly 800,000 Americans experience a stroke every year and 87% of those are ischemic strokes. Currently, the only way to minimize stroke-induced cell death is to remove the clot as soon as possible. A treatment to help brain cells survive a stroke-induced lack of oxygen and glucose could dramatically improve patient outcomes, but no such neuroprotective agents for stroke patients exist.

 

In the fight against brain damage caused by stroke, the authors turned to an unlikely source of inspiration: hibernating ground squirrels. While the animals’ brains experience dramatically reduced blood flow during hibernation, just like human patients after a certain type of stroke, the squirrels emerge from their extended naps suffering no ill effects. Excitingly, a potential drug has been identified that could grant the same resilience to the brains of ischemic stroke patients by mimicking the cellular changes that protect the brains of those animals. The study was published online on 16 November  2017, in The FASEB Journal, the official journal of the Foundation of American Societies for Experimental Biology.

 

Recently, the authors of the study, found that a cellular process called SUMOylation goes into overdrive in a certain species of ground squirrel during hibernation. Dr. authors suspected this was how the animals’ brains survived the reduced blood flow caused by hibernation, and subsequent experiments in cells and mice confirmed his suspicions. SUMOylation occurs when an enzyme attaches a molecular tag called a Small Ubiquitin-like Modifier (SUMO) to a protein, altering its activity and location in the cell. Other enzymes called SUMO-specific proteases (SENPs) can then detach those tags, thereby decreasing SUMOylation. In the current study, the authors examined whether any of over 4,000 molecules from the NCATS small molecule collections could boost SUMOylation by blocking a SENP called SENP2, which would theoretically protect cells from a shortage of life-sustaining substances. The authors first used an automated process to examine whether the compounds prevented SENP2 from severing the connection between a tiny metal bead and an artificial SUMO protein. This system, along with computer modeling and further tests performed both in and outside of cells, whittled the thousands of candidate molecules down to eight that could bind to SENP2 in cells and were non-toxic. Two of those – ebselen and 6-thioguanine – were then found to both boost SUMOylation in rat cells and keep them alive in the absence of oxygen and glucose. A final experiment showed that ebselen boosted SUMOylation in the brains of healthy mice more than a control injection. 6-thioguanine was not tested because it is a chemotherapy drug with side effects that make it unsuitable as a potential stroke treatment. The authors now plan to test whether ebselen can protect the brains of animal models of stroke.

 

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