Molecular biomarkers for preeclampsia

Preeclampsia is a sudden pregnancy complication that can interfere with the blood flow to the placenta and possibly to the fetus, it can lead to low birth weight, prematurity and death. It is also a leading cause of maternal mortality. A new Tel Aviv University study identifies novel molecular biomarkers of preeclampsia, signaling the potential for an early diagnostic blood test.

Research for the study was led by Dr. Noam Shomron and Prof. Moshe Hod and conducted by Liron Yoffe and other lab members, all affiliated with TAU's Sackler School of Medicine, and in collaboration with Prof. Kypros Nicolaides of King's College, London. Preeclampsia is a serious disease that endangers the health, sometimes even the lives, of the mother and the fetus.

The causes of  preeclampsia is unknown if caught in time it has a simple and proven remedy: low doses of aspirin administered from the 16th week until the end of pregnancy. Medical practitioners have assessed a woman's risk of preeclampsia by referring to previous pregnancies, blood pressure levels and other general symptoms. Blood test could predict preeclampsia and, in turn, allow doctors to provide treatment that would prevent the  onset of the disease.

Researchers examined the blood samples from thousands of pregnant women in their first trimester, the team then narrowed their focused to 75 specific blood samples: 35 taken from women who eventually contracted preeclampsia, and 40 taken from those who completed their pregnancies in full health. The researchers extracted the RNA molecules (snippets of molecular information present in human cells) from the plasma of the samples and sequenced these using Next Generation Sequencing (NGS).

The scientists discovered the new biomarkers by analyzing the data using computational methods that included statistical analyses and machine learning algorithms. They identified 25 small RNA molecules that were differentially expressed between the preeclampsia and the control groups. Based on those RNA molecules, they developed a model for the classification of preeclampsia samples.

These findings indicate the predictive value of circulating small RNA molecules in the first trimester, and lay the foundation for producing a novel early non-invasive diagnostic tool for preeclampsia, which could reduce the life-threatening risk for the mother and fetus.
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How brain imaging redefine intelligence

High-tech scans of the resting human brain can provide a new way to define and interpret the brain's actual mental capacity, new research suggests. NYU School of Medicine researchers used a specialized imaging technology to measure patients' brains for entropy , the variety of nerve circuits used to interpret the surrounding world.

Part of theories on human consciousness, the concept of entropy has become a greater research focus with recent improvements in the ability of functional magnetic resonance imaging (fMRI) to track chemical activity patterns in the brain.

By analyzing fMRI images in every region of the brains in 892 American men and women, the study authors linked greater entropy to more versatile processing of information. This is considered a key aspect of intelligence, researchers say, because of the large volume of sensory information coming into the brain from its environment.

Functional MRI scans of brain entropy are a new means to understanding human intelligence," says study lead investigator Glenn Saxe, MD, a professor in child and adolescent psychiatry at NYU School of Medicine and a member of NYU Langone Health's Neuroscience Institute.

Human intelligence is so meaningful because it is about the capacity to understand whatever may come, when there is no way beforehand to know what may come. An intelligent brain has to be flexible in the number of possible ways its nerve cells, or neurons, may be rearranged.

Functional MRI scans use magnetic fields and radio waves to measure subtle changes in blood flow to detect which brain cells and circuits are active or inactive. As part of the study, people were tested when their brains and minds were resting (not unengaged in a particular task) to get a base reading. Study participants had their brains imaged as they enrolled in the Harvard-based Brain Genomics Superstruct study over the last decade, with the stored images forming the foundation of the NYU team's analysis.

Researchers compared hundreds of fMRI scans taken milliseconds apart. The scans revealed the number of possible combinations of electrically active brain cells available to interact with each other in specific regions of the brain. The research team then used mathematical models validated by past studies to arrive at reliable, statistical entropy scores based on how well one set of active nerve-cell combinations captured by one image predicted those in the next image. Experts say the activity level of the estimated 100 billion neurons in the brain depends on how much sensory information is being processed at any instant, with many often inactive.

Scientists next compared their statistical measures of relatively higher or lower entropy with participants' scores on two standard IQ tests: the Shipley-Hartford test, which gauges verbal skills, and the Wechsler test, which assesses problem-solving abilities. If brain entropy could offer useful insight into intelligence, then it should track closely with IQ scores.

People with average intelligence have an IQ score of about 100, with current study participants having an above-average IQ, at 108. Study participants ' entropy scores were strongly tied to IQ. Using standard statistical techniques that were performed two different ways to ensure accuracy, the researchers found that higher entropy was significantly related to the brain regions where previous research has shown it matters most.

 Entropy scores closely matched IQ scores from the Shipley-Hartford test for the left side of the middle brain (the left inferior temporal lobe), which is tied to learning speech. Similarly, entropy scores tracked closely with those from the Wechsler test for the front region of the brain (bilateral anterior frontal lobes), a known center for organization, planning, and emotional control.
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Why people get aggressive after drinking

Researchers have used magnetic resonance imaging (MRI) scans that measure blood flow in the brain to understand why people become aggressive and violent after drinking alcohol. After only two drinks, the researchers noted changes in the working of the prefrontal cortex of the brain, the part involved in tempering a person's levels of aggression. The study was led by Thomas Denson of the University of New South Wales in Australia in the journal Cognitive, Affective, & Behavioral Neuroscience.

According to most theories, alcohol-related aggression is caused by changes in the prefrontal cortex. However, there is a lack of substantial neuroimaging evidence to substantiate these ideas. In this study, Denson and his team recruited fifty healthy young men. The participants were either given two drinks containing vodka, or placebo drinks without any alcohol. While lying in an MRI scanner, the participants then had to compete in a task which has regularly been used over the past 50 years to observe levels of aggression in response to provocation.

The functional magnetic resonance imaging allowed the researchers to see which areas of the brain were triggered when the task was performed. They could also compare the difference in scans between participants who had consumed alcohol and those who hadn't. Being provoked was found to have no influence on participants' neural responses. However, when behaving aggressively, there was a dip in activity in the prefrontal cortex of the brains of those who had consumed alcoholic drinks. This dampening effect was also seen in the areas of the brain that are involved reward. Also, heightened activity was noted in the hippocampus, the part of the brain associated with people's memory.

Although there was an overall dampening effect of alcohol on the prefrontal cortex, even at a low dose of alcohol there is a significant positive relationship between dorsomedial and dorsolateral prefrontal cortex activity and alcohol-related aggression. These regions may support different behaviors, such as peace versus aggression, depending on whether a person is sober or intoxicated.

The results are largely consistent with a growing body of research about the neural basis of aggression, and how it is triggered by changes in the way that the prefrontal cortex, the limbic system and reward-related regions of the brain function. The results of the current study are also consistent with several psychological theories of alcohol-related aggression.
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Links between migraine and cardiovascular problems

Migraine is associated with increased risks of cardiovascular problems including heart attacks, stroke, blood clots and an irregular heart rate. Migraine should be considered a potent and persistent risk factor for most cardiovascular diseases in both men and women. Previous studies have suggested a link between migraine and stroke and heart attacks, particularly among women.

Researchers from Aarhus University Hospital, Denmark and Stanford University, USA set out to examine the risks of heart conditions including heart attacks; stroke; peripheral artery disease (narrow arteries which reduce blood flow to limbs); blood clots and fast and irregular heart rates in people who experience migraines compared with people who don't. The researchers collected patient data from the Danish National Patient Registry over a 19 year period, from 1995 to 2013.

They compared data from over 51,000 people who had been diagnosed with migraine with over 510,000 people who were migraine free. For each person with migraine, they matched 10 people of the same age and gender who were migraine free. The average age for migraine diagnosis was 35 years, and 71% of participants were women. Over a period of 19 years, the researchers found that migraine was positively associated with heart attack, stroke, blood clots and irregular heart rate.

For example, for every 1,000 patients, 25 patients with migraine had a heart attack compared with 17 migraine free patients and 45 patients with migraine had an ischaemic stroke (blood clot in the brain) compared with 25 migraine free patients. These associations persisted after taking account of body mass index and smoking. No meaningful association was found with peripheral artery disease or heart failure.

The associations, particularly for stroke, were stronger in the first year of diagnosis than the long term, in patients with migraine aura-warning signs before a migraine, such as seeing flashing lights.
People with migraine often use anti-inflammatory drugs, which are associated with increased risks of heart problems, while immobilisation related to migraine attacks may increase the risk of blood clots.

They note that current guidelines do not recommend use of anti-clotting drugs such as aspirin to treat migraine, but call on clinicians to consider whether patients at particularly high risk of heart disease would benefit from anticoagulant treatment. Migraine should be considered a potent and persistent risk factor for most cardiovascular diseases.
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High salt diet hobbles the brain

A new study has shown that mice fed with a very high-salt diet experienced declined blood flow to their brain, the integrity of blood vessels in the brain suffered, and performance on tests of cognitive function plummeted.

Researchers found that those effects were not as long has been widely believed, a natural consequence of high blood pressure. Instead, they appeared to be the result of signals sent from the gut to the brain by the immune system.

The study, conducted by researchers at Weill Cornell Medicine in New York. The research sheds light on a subject of keen interest to scientists exploring the links between what we eat and how well we think, and the mediating role that the immune system plays in that communication.

This suggests that even before a chronic high-salt diet nudges blood pressure up and compromises the health of tiny blood vessels in the brain, the oversalted gut is independently sending messages that lay the groundwork for corrosion throughout the vital network.

In the small intestines of mice, the authors of the new research found that a very high-salt diet prompted an immune response that boosted circulating levels of an inflammatory substance called interleukin-17. These high levels of IL-17 set off a cascade of chemical responses inside the delicate inner linings of the brain's blood vessels.

The result in mice fed with the high-salt diet: blood supply to two regions crucial for learning and memory-the cortex and hippocampus slowed markedly. And mental performance slid. Compared to mice fed a diet lower in salt, the maze-running skills of the mice who consumed high-salt levels faltered, and they failed to respond normally to whisker stimulation, or a new object in their cage.

In mice, that evidence of cognitive impairment was apparent even in the absence of high blood pressure. The immune system's role in sending signals between brain and gut is also seen in diseases like multiple sclerosis, rheumatoid arthritis, psoriasis and inflammatory bowel disease-all disorders that are linked to poor functioning of the brain's blood vessels.
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Valsartan for treating high blood pressure

Valsartan is an angiotensin II receptor antagonist. Valsartan keeps blood vessels from narrowing, which lowers blood pressure and improves blood flow. It is used to treat high blood pressure (hypertension) in adults and children who are at least 6 years old. Valsartan is also used in adults to treat heart failure, and to lower the risk of death after a heart attack. It is sometimes given together with other blood pressure medications.

If you have diabetes, do not use valsartan together with any medication that contains aliskiren (Amturnide, Tekturna, Tekamlo, Valturna). Before taking this medicine. Do not use valsartan if you are allergic to it. You may take valsartan with or without food. Take the medicine at the same time each day. If a child taking valsartan cannot swallow a capsule whole, your pharmacist can mix the medicine into a liquid. Shake this liquid well just before you measure a dose.

Measure the liquid with a special dose-measuring spoon or medicine cup, not with a regular table spoon. You may have very low blood pressure while taking valsartan. Call your doctor if you are sick with vomiting or diarrhea, or if you are sweating more than usual. Drinking alcohol can further lower your blood pressure and may increase certain side effects of valsartan. Do not use potassium supplements or salt substitutes while you are taking valsartan, unless your doctor has told you to.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall. Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. In rare cases, valsartan can cause a condition that results in the breakdown of skeletal muscle tissue, leading to kidney failure. Call your doctor right away if you have unexplained muscle pain, tenderness, or weakness especially if you also have fever, unusual tiredness, and dark colored urine.
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Anger causes untimely death

Researchers have discovered that angry men aged 20 to 40 were one-and-a-half times more likely to be dead 35 years later than those who were calmer. They believe this is due to a number of factors linking stress to physiological damage. The frequent release of adrenaline during periods of stress damages DNA, which could lead to life-threatening illnesses such as multiple sclerosis.

Feelings of anger produce a heightened response in the amygdala, the part of the brain associated with survival instincts. Angry emotions prompt the amygdala to signal a heightened state of anxiety to the rest of the brain and the body, increasing blood flow to the limbs and heart, which makes relaxation impossible.

Those exposed to anger-inducing stimuli without discussing how it made them feel are more likely to experience insomnia than those who engage in an emotional ‘debrief’, according to neuroscientists. Writing the cause of anger frees up the space in the head, dampening the fear response and encouraging relaxation.

 Emotions such as excitement or anger result in the release of stress hormones cortisol, adrenaline and testosterone, which put the body into flight-or-flight mode. The chemical surge increases blood flow to the brain and triggers the swelling of both blood vessels and nerves surrounding the brain. The pressure can result in tension and headaches.

Highly hostile individuals performed significantly worse on a simple inhalation task than those who were rated less hostile. When you are angry, neurotransmitters and hormones are sent through the bloodstream which, in turn, increase both the heart rate and muscle tension. Frequent occurrence of this reaction puts a strain on neurons in the hypothalamus, the brain’s ‘stress control centre’, meaning that it becomes harder for the neurons to switch off. And the ‘happy hormone’ serotonin is significantly depleted in some aggressive individuals.

Too much cortisol in the body – released by adrenal glands during angry outbursts can cause an imbalance in blood sugar, repress the thyroid and even decrease bone density. When released initially, cortisol triggers an anti-inflammatory response by the immune system, but prolonged increase of the hormone makes the body more susceptible to viruses. As blood pressure rises thanks to a surge in adrenaline, the heart beats faster, increasing the risk of potentially fatal abnormal heart rhythms. Adrenaline also signals for the release of platelets, which can trigger blood clots or block arteries – particularly dangerous if arteries are restricted by a build-up of cholesterol.

Studies have shown that men in particular who score highly on trait anger scales are three times more likely to suffer from general heart disease. Once the ‘fight or flight’ signal has been issued by the brain, blood supply is directed to areas needed for action such as the limbs. That means blood supply to the digestive system is reduced, with a reduced amount of oxygen provided to keep vital ‘good’ bacteria in the gut alive. A dampened immune system can lead to a weakened gut lining, increasing vulnerability to harmful bacteria entering the area.

Heightened stress reduces the amount of available glucocorticoids -the hormone involved in the synthesis of the skin-plumping compound collagen. Lack of collagen contributes towards saggy, wrinkled skin. The weakened immune system caused by stress responses increases inflammatory reactions to pathogens underneath the skin.

Enhanced periods of anger disrupt the skin-barrier function, making it easier for allergens to penetrate and resulting in skin conditions such as dermatitis and psoriasis. Repressing, rather than expressing anger puts you at an higher risk of developing health problems. This increased risk of hypertension for angry individuals who tended to keep their anger below a level of consciousness. By repressing emotion, excess stress hormones remain in the emotion-processing areas of the brain for longer period making physical reactions chronic.
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Regeneration of blood vessels

A new study led by researchers identifies a signaling pathway that is essential for angiogenesis, the growth of new blood vessels from pre-existing vessels. The finding may improve current strategies to improve blood flow in ischemic tissue, such as that found in atherosclerosis and peripheral vascular disease associated with diabetes.

The research shows that the formation of fully functional blood vessels requires activation of protein kinase Akt by a protein called R-Ras, and this mechanism is necessary for the formation of the hallow structure, or lumen, of a blood vessel.This showed the biological process needed to increase blood flow in ischemic tissues.

Research team used a combination of 3D cell culture and living tissue to show that vascular endothelial growth factor VEGF promotes vascularization, but the vessel structures formed are chaotic, unstable and non-functional. Functional vessels need to have a lumen; a pipe-like opening that allows oxygenated blood and nutrients to travel through the body and VEGF alone cannot fully support the formation of such a vessel structure.

 VEGF activates Akt to induce endothelial cells to sprout. Then, R-Ras activates Akt to induce lumen formation. The second step involving Akt activation by R-Ras stabilizes the microtubule cytoskeleton in endothelial cells, creating a steady architecture that promotes lumen formation. VEGF and R-Ras activation of Akt signaling are complementary to each other, both are necessary to generate fully functional blood vessels to repair ischemic tissue.  
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Lack of oxygen delays brain maturation in preterm infant

Premature infants are at risk of a broad spectrum of life-long cognitive and learning disabilities, these conditions were believed to be the result of lack of blood flow to the brain. Reserchers analyzed the response of fetal subplate neurons - cells that play a critical role in regulating preterm brain function and connectivity to disturbances of brain oxygenation.

When the developing brain was exposed to lower than normal rates of oxygen for as short as twenty minutes, subplate neurons showed major long-term disturbances just one month following exposure.

The brief exposure to low oxygen occurs frequently in preterm babies receiving care in a neonatal intensive care unit and this result explains the long-term complications that these preterm babies sustain as they grow older, which include significant challenges with learning, memory and attention.

Clinicians must be careful how they interact with, stimulate and handle preterm babies during intensive care treatment. This will lead to better management transient low- oxygen states and determine what the preterm brain can and cannot tolerate.
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Gata4 repairs a broken heart

Blood flow to the heart ceased during heart attack, this leads to death of the heart muscles, heart muscle does not regenerate; it replaces dead tissue with scars made of fibroblasts that do not pump blood to the heart.

People who had severe heart attack will develop heart failure, restoring cardiac function by reprogramming scar tissue into cardiomyocyte-like can reduce risk of heart failure.

Researchers has shown that applying a cocktail made of transcription factors Gata4, Mef2c and Tbx5 GMT results in less scar tissue, or fibrosis, and up to a fifty percent increase in cardiac function in small animal models of the disease.

This result was presumed to be mostly a consequence of the reprograming of heart fibroblasts into cardiomyocyte-like cells. They noticed that reduced fibrosis and improved cardiac function far exceeded the extent of induced new cardiomyocyte-like cells.

The research team investigated how the GMT cocktail activated mechanisms that reduced fibrosis. They discovered that of the three components in the GMT cocktail, only Gata4 was able to reduce post-heart attack fibrosis and improve cardiac function in a rat model of heart attack.

Adding Gata4 to rat fibroblasts showed an reduced expression of Snail, the master gene of fibrosis. Gata4 plays a complex role in heart regeneration: as part of the GMT cocktail, it contributes to the reprograming of fibroblasts into cardiomyocyte-like cells. It can also contributes to the development of an enlarged heart and decrease cardiac fibrosis.
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Low blood flow in the brain may be a sign of dementia

High blood pressure and decreased blood flow in the brain may cause the build-up of dangerous amyloid plaque in the brain. Having problems with the blood vessels in the brain may affect thinking, cognition and memory.

Brain's blood vessels work like a plumbing system that distributes oxygen to every parts of brain cells and remove waste materials from the cells.

The brain relaxes its vessels to maintain constant blood flow as it adjusts for changes in blood pressure, but the brain vessels in Alzheimer's patients prevent blood flow and allow amyloid to get to the brain cells.

Alzheimer's patients have lower blood flow in their brains than the people without the disease. They experience cognitive decline and memory loss that leads to dementia.

Taking blood pressure lowering drugs can reduce the effects on memories of affected people because the drugs can cross the blood-brain barrier and prevents the toxins from getting to the brain.
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