Medical News Today: Researchers discover new autoinflammatory condition

A team of specialists from Australia and the United States has identified a new autoinflammatory condition in humans. They also understand what causes it, which can help researchers find an adequate treatment.

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Researchers have identified a new autoinflammatory condition, which they have named CRIA syndrome.

Autoimmune conditions occur when the body's immune response becomes abnormally activated. When this happens, it turns against healthy cells instead of just reacting to potentially harmful agents, such as viruses or dangerous bacteria, as it should.

Recurrent fevers with unclear causes and widespread inflammation characterize such conditions.

While they are not widespread, doctors often find autoinflammatory conditions challenging to diagnose. This is problematic, as these conditions can severely impact a person's well-being and quality of life.

So far, researchers have identified only a handful of autoinflammatory conditions. They include familial Mediterranean fever, cryopyrin-associated periodic fever syndrome, Still's disease, and periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome (PFAPA).

Recently, however, a team of experts from the University of Melbourne in Australia and the National Institutes of Health (NIH) in Bethesda, MD, has discovered another autoinflammatory condition.

The researchers have named it "cleavage-resistant RIPK1-induced autoinflammatory (CRIA) syndrome." They explain how they discovered it and what they think might be the path towards a treatment in a study paper in the journal Nature.

A 'remarkable' finding

The researchers' interest was piqued when members of three different families sought treatment for a mysterious autoinflammatory disorder whose main characteristics were states of fever and swelling of the lymph nodes.

These individuals reported that they first experienced the symptoms in childhood, though they had persisted through adulthood.

To try and find out what caused this unknown autoinflammatory condition, the researchers looked to the individuals' DNA. The investigators found the condition's root cause when they analyzed the exomes in DNA samples from the people who had CRIA syndrome. The exome is part of a person's genetic material that encodes proteins.

By looking at the samples, the researchers made the intriguing discovery that all the people who had CRIA syndrome had a mutant RIPK1 gene.

This gene encodes the specialized protein (enzyme) of the same name, which plays a crucial role in regulating programmed cell death (necroptosis).

"Cell death pathways have developed a series of inbuilt mechanisms that regulate inflammatory signals and cell death because the alternative is so potentially hazardous," explains Dr. Najoua Lalaoui, one of the lead researchers involved in this study.

"However, in this disease, the mutation in RIPK1 is overcoming all the normal checks and balances that exist, resulting in uncontrolled cell death and inflammation," she points out.

The finding provided the key to understanding how the newly discovered autoinflammatory condition unfolded, emphasizes another one of the lead authors, Dr. Steven Boyden.

"We sequenced the entire exome of each patient and discovered unique mutations in the exact same amino acid of RIPK1 in each of the three families. It is remarkable, like lightning striking three times in the same place. Each of the three mutations has the same result — it blocks cleavage of RIPK1 — which shows how important RIPK1 cleavage is in maintaining the normal function of the cell."

Dr. Steven Boyden

On track for finding a treatment?

Although the condition is a newcomer on the clinical stage and has no apparent treatment, the specialists who discovered it argue that the answer to CRIA syndrome most likely lies in the cause that drives it.

"Understanding the molecular mechanism by which CRIA syndrome causes inflammation affords an opportunity to get right to the root of the problem," notes co-lead author Dr. Dan Kastner, who is one of the leading specialists in inflammatory conditions.

Dr. Kastner explains that he and his colleagues have already started looking for possible ways of treating this condition. In fact, they have already treated some people with CRIA syndrome with anti-inflammatory drugs, such as high dosage corticosteroids and biologics.

While some people demonstrated significant improvement following their treatment, others did not improve or experienced side effects.

But the researchers remain confident that they will find an appropriate therapy for everyone affected by the newly discovered condition.

"RIPK1 inhibitors may be just what the doctor ordered for these patients," says Dr. Kastner. "The discovery of CRIA syndrome also suggests a possible role for RIPK1 in a broad spectrum of human illnesses, such as colitis, arthritis, and psoriasis."

And there is further good news — RIPK1 inhibitors are already available to researchers, so ongoing tests may be able to further refine and perfect treatments on a case by case basis.

Original Article

Medical News Today: Unhealthful diet linked with vision loss later in life

A new study spanning nearly 2 decades has found a link between an unhealthful diet and vision loss in older age. Should we be keeping more of an eye on what we eat?

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A diet rich in fats and red meat may contribute to AMD.

A robust body of research has shown that a diet rich in red meat, fried foods, high fat dairy, processed meats, and refined grains is bad for the heart and linked to the development of cancer.

However, not many people consider the impact of diet on their eyesight.

A new study, now appearing in the British Journal of Ophthalmology, has found a link between a diet rich in unhealthful foods and age-related macular degeneration (AMD).

AMD is a condition that impacts the retina with age, blurring central vision. Central vision helps people see objects clearly and perform everyday activities such as reading and driving.

According to the Centers for Disease Control and Prevention (CDC), in the United States, around 1.8 million people aged 40 and above are living with AMD, and another 7.3 million have a condition called drusen, which usually precedes AMD.

The CDC also explain that "AMD is the leading cause of permanent impairment of reading and fine or close-up vision among people aged 65 years and older."

Now, the new study — which was the first to look at dietary patterns and the development of AMD over time — has found an association between an unhealthful diet and AMD.

Senior study author Dr. Amy Millen, of the University at Buffalo in New York, told Medical News Today, "Most people understand that diet influences cardiovascular disease risk and risk [of] obesity; however I'm not sure the public thinks about whether or not diet influences one's risk [of] vision loss later in life."

Although research has shown links between certain foods and nutrients and AMD — for example, some studies have suggested that high dose antioxidants may slow progression — there has been less research into dietary patterns as a whole.

Furthermore, studies that have looked at dietary patterns have focused on late stage risk — that is, the point at which the condition becomes vision threatening — rather than early and late stage disease.

"We wanted to examine how the overall pattern of one's diet may predict later development of AMD, both early onset and late stage disease," said Dr. Millen.

Unhealthful diet raises AMD risk by threefold

The study looked at the development of early and late AMD in participants of the Atherosclerosis Risk in Communities study, which looked at arterial health over 18 years (1987–1995).

Using data on 66 different food types, the researchers identified two diet patterns: one they dubbed "Prudent," or healthful, and one they dubbed "Western," which included a high intake of "processed and red meat, fried food, dessert, eggs, refined grains, high fat dairy, and sugar sweetened beverages."

Although the researchers found no link between early AMD and dietary patterns, they found that the incidence of late AMD was three times higher among those with a Western eating pattern.

"What we observed in this study was that people who had no AMD or early AMD at the start of our study, and reported frequently consuming [unhealthful] foods, were more likely to develop vision threatening, late stage disease approximately 18 years later," says Dr. Millen.

Prevention is better than cure

Early stage AMD has no symptoms, so a person may not know that have it. Also, although not everyone develops late stage AMD, for those who do, it can be costly and invasive to treat.

There are two forms of late stage AMD. One is called wet AMD, or neovascular AMD, which healthcare professionals tend to treat by injecting antivascular growth factors.

The other is called dry AMD, or geographic atrophy, which occurs when the photoreceptor cells die without neovascularization. There is no effective treatment for this form of AMD.

"We would like the public to realize that diet is important to their vision," said Millen.

"The clinical take-home message is that dietary intake likely makes a difference in determining central vision loss later in life. If a person has early onset AMD, it is in their best interest to eat foods we identified as part of the Western diet pattern in moderation."

Dr. Amy Millen

Original Article

Medical News Today: Could MDMA help treat mental health conditions?

Ecstasy — or methylenedioxymethamphetamine (MDMA) — is a recreational drug that is illegal in the United States. However, some researchers believe that it could aid in mental health therapy. A new study in mice puts this idea to the test.

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New research in mice investigates what gives MDMA its positive effects on sociability.

MDMA is a mind-altering drug that can be popular at parties, as it boosts energy and especially empathy, making people feel more connected and safe around others, even if they are strangers.

In the U.S., MDMA is classed as a Schedule I drug, which makes it illegal, as a substance "with no currently accepted medical use and a high potential for abuse."

However, this classification came after some psychiatrists had used the drug for therapeutic purposes, for many years, to help individuals who were struggling with communication feel more at ease and able to talk about their problems.

The fact that the drug can become addictive made it fall from favor, and it acquired its illegal status in 1985. Recently, though, more and more researchers are beginning to ask whether MDMA can ever be used safely in therapy.

Earlier this month, scientists from Stanford University, in California, and the Albert Einstein College of Medicine, in New York, published a paper in the journal Science Translational Medicine, detailing the findings of a study that they had conducted in mice.

In this study, the team aimed to determine how MDMA causes an individual to become more sociable. They also hoped to find out which doses, if any, could provide the positive effects with minimal risk of addiction and other threats to health.

"We've figured out how MDMA promotes social interaction and showed that [this is] distinct from how it generates abuse potential among its users."

Senior author Dr. Robert Malenka

MDMA triggers the release of serotonin

To understand what differentiates MDMA's positive effects from its potential to become addictive, the researchers looked to the brain circuit that underlies addiction: the reward circuit.

"The brain's reward circuitry tells us something is good for our survival and propagation. It evolved to tell us food is good when we're hungry, water is good when we're thirsty, and warmth is good when we're cold. For most of us, hanging out with friends is fun because, over the course of our evolution, it's promoted our survival," explains Dr. Malenka.

But, he adds, the same circuit can end up reinforcing that something unhealthy is highly desirable. When we take an addictive drug, the researcher explains, the substance stimulates brain cells to release the "happy hormone" dopamine.

Dopamine then acts on a brain region that is key to the reward system, the nucleus accumbens, which, in turn, sends out reward signals. These reinforce the sense that the substance is something desirable and that we need to seek it out.

"Drugs of abuse trick our brains by causing an unnatural dopamine surge in the nucleus accumbens. This massive increase is much higher and more rapid than the one you get from eating ice cream or having sex," Dr. Malenka points out.

But which neural mechanisms does MDMA tap into to achieve its prosocial effects?

Dr. Malenka and colleagues explain that the prosocial effects of the drug most likely result from the release of serotonin, a hormone that helps regulate many functions, including mood, sexual desire, and social behavior.

MDMA stimulates neurons to release serotonin into the dorsal raphe nucleus, a part of the brain that communicates with the nucleus accumbens.
By this point in their study, the researchers had yet to discover which doses of MDMA could trigger prosocial behaviors without stimulating addictive responses.

Can dosage aid bonding without addiction?

At a very low dose of 2 milligrams per kilogram (mg/kg), mice that received the substance showed no improvements in sociability. However, when the researchers upped the dose to 7.5 mg/kg — still a low dose — the mice became more sociable.

"You can't ask mice how they're feeling about other mice, but you can infer it from their behavior," Dr. Malenka explains.

After having administered either a low dose of MDMA or a saline solution placebo, the researchers placed each mouse in a space that gave them options — to spend time alone or with another, MDMA-free, mouse.

The investigators found that the mice that had received 7.5 mg/kg of the drug would remain interested in the fellow rodent for at least 30 minutes, while those in the placebo group would invariably get bored after 10 minutes.

And, lead author Dr. Boris Heifets points out, "Giving MDMA to both mice enhanced the effect even further."

"It makes you wonder if maybe [in a human therapy context] the therapist should also be taking MDMA," Dr. Heifets notes.

But how did the investigators know that the 7.5 mg/kg dose did not also trigger addiction? The researchers explain that individuals with addiction — and this goes for humans and rodents — tend to repeatedly seek out the same spaces where they had enjoyed themselves.

The team gave the mice the same dose of MDMA as before and placed them in one room of an environment that had two rooms. The next day, they placed the mice in that environment again, to see whether they would choose to be in the room where they had received the drug.

The rodents, however, showed no preference for either room, suggesting that the neural mechanisms of addiction had not been set in motion. The same was not true for mice who had received a higher dose of the drug: 15 mg/kg.

An MDMA alternative with its own dangers

When researchers blocked a specific type of serotonin receptor present in large numbers in the nucleus accumbens, they saw that this stopped MDMA from having a prosocial effect in mice. This confirmed that serotonin had been responsible for the boost in sociability.

They also found that they could use a drug to trigger the release of serotonin, but — unlike MDMA — not dopamine, to boost sociability in mice without the risk of addiction.

There is, however, a catch. The drug that achieved this effect was d-fenfluramine, which was once popular as a weight loss aid. It fell out of use in the late 1990s, when researchers confirmed that the drug could cause severe, life threatening cardiovascular problems.

Thus, the research team emphasizes that neither MDMA, which has the potential for addiction, nor d-fenfluramine, which can impact vascular health, should ever be used as daily therapeutics.

They do, nevertheless, argue that a one-off dose would likely be a safe way to help an individual open up with their therapist.

Original Article

Medical News Today: Should we all be eating more protein?

A recent review and meta-analysis investigating protein intake conclude that consuming the recommended daily allowance is fine for most people, most of the time. However, more protein is not necessarily beneficial.

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Protein supplements are increasingly popular.

Many of us enthusiastically indulge in holiday treats, which means that come New Year's Day, beginning a weight loss program is a common resolution.

An increase in the consumption of protein — often over the recommended daily allowance — is the cornerstone of many diets, but does eating more protein make sense for everyone?

A new study by nutrition scientists at Purdue University in West Lafayette, IN, finds that increasing the intake of protein only provides benefits in certain circumstances. The findings of the research appear in Advances in Nutrition.

The bottom line is that if you are not explicitly dieting for weight loss or weight training, there is no clear benefit to consuming more protein than the minimum daily requirements that the United States Department of Agriculture (USDA) have established.

"[T]here is so much encouragement, advertising, and marketing for everyone to eat higher protein diets, and this research supports that, yes, under certain conditions, including strength training and weight loss, moderately more protein may be helpful, but that doesn't mean more is needed for everybody at all times," explains the lead author, Joshua Hudson.

A normal amount of protein

Commenting on the study's narrow focus, Hudson says:

"This research was not designed to assess whether or not adults would benefit from consuming more protein than they usually consume. This distinction is important because the recommended dietary allowance is the standard against which to assess nutrition adequacy; however, most adults consume more protein than what is recommended."

According to the USDA's Dietary Reference Intakes (DRI), the desired daily amount of protein is 0.8 grams (g) per kilogram of body weight, which equates to about 0.36 g of protein per pound each day. Based on this, 56 g per day is suitable for the average, generally healthy sedentary male, while a similar female should aim for 46 g. It is important to note that these recommendations do not apply to people with type 2 diabetes.

The USDA list a range of food sources from which to get that protein, including seafood, meats, poultry, eggs, nuts, seeds, and soy products.

The study's methodology

Hudson and his colleagues began by looking at more than 1,500 articles on nutrition that they found in nutritional databases. From these, they identified 18 papers for closer examination.

The authors chose these papers for their inclusion of healthy adults and their focus on certain topics, including protein consumption, physical activity, and weight loss. Together, the research encompassed 22 interventions involving 981 individuals. The sources of protein that the participants consumed included lean and minimally processed meats, dairy, eggs, nuts, seeds, and legumes.

The data revealed that for everyday life — when individuals are neither gaining nor losing weight — eating more than the recommended amount of protein does not do anything for body composition.

The study reports no harmful consequences, simply no effect at all, be it negative or positive.

A higher intake of protein only enhances lean mass in people who are consciously dieting or engaging in weight training.

Too little protein, however, is a problem, says study co-author Campbell, who explains, "This research is clinically more important for women and especially older women who are known to typically consume lower amounts of protein and should be maintaining a healthy body weight and regularly strength training."

As far as holiday eating goes, Campbell offers the following advice: "If you are going to start losing weight, don't cut back across all foods you usually consume, because you'll inadvertently cut back protein. Instead, work to maintain, or even moderately increase protein-rich foods. Then, cut back on the carbs and saturated fat-containing foods."

Original Article

Medical News Today: Cholesterol levels in young adults can predict heart disease risk

A recent study investigates the relationship between cholesterol levels in young adulthood and cardiovascular risk in later life — with interesting recommendations for further research.

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A recent study looks at the long term impact of high cholesterol levels.

Research has already well documented that high cholesterol levels can lead to heart disease, the leading cause of death in the United States, and stroke, the fifth leading cause of death.

Cholesterol is a fatty substance that the liver and foods we eat, such as eggs, cheese, and certain meat products produce.

Cholesterol is necessary for the body to function. However, too much "bad" cholesterol, which is also called low-density lipoprotein (LDL), can clog the arteries with a fatty buildup, increasing the risk of heart attack, stroke, or peripheral artery disease.
Scientists have also linked high total cholesterol to overweight, lack of exercise, smoking, and alcohol consumption.

More than 12% of adults in the U.S. aged 20 years and over have total cholesterol levels above 240 milligrams per deciliter (mg/dl), which doctors consider high. Of children and adolescents aged 6–19 years, some 7% have high total cholesterol.

High-density lipoprotein (HDL) is "good" cholesterol and helps to sweep LDL from the arteries back to the liver, which removes it from the body.

A long look at lipids

A new, comprehensive study, appearing in The Lancet, follows almost 400,000 people in 19 countries for up to 43.5 years (1970–2013). The findings shine a spotlight on the link between bad cholesterol (non-HDL) levels in people under 45 years of age and the long-term risk of heart disease and stroke.

Set apart from previous studies, this observational and modeling study, which looked at individual level data, suggests that elevated non-HDL cholesterol levels at a younger age can predict cardiovascular risk at 75 years of age.

The study used data from 38 studies carried out in the U.S., Europe, and Australia.

Of the nearly 400,000 individuals that the study followed, none had cardiovascular disease at the start. The scientists tracked the participants over decades and took details of any heart disease event, fatal or otherwise, or stroke.

In total, there were 54,542 incidents of heart disease, fatal or non-fatal, and stroke.

When researchers analyzed the data for all age groups and both sexes, they saw that the risk of heart disease or stroke dropped continuously as non-HDL levels dropped. In fact, those with the lowest non-HDL levels, — which the scientists defined as 2.6 millimoles (mmol) non-HDL cholesterol per liter — had the least risk.

The highest long-term risks of heart and artery disease were in those younger than 45 years old.

"This increased risk in younger people could be due to the longer exposure to harmful lipids in the blood," says Prof. Barbara Thorand, of the German Research Center for Environmental Health in Neuherberg.

Study suggests early intervention vital

The study confirmed that the level of non-HDL and HDL cholesterol in the blood played a significant part in predicting the risk of cardiovascular disease over time.

Researchers used data to create a model for people aged 35–70 years that could estimate the chances of a heart event by age 75 years. It factored in sex, age, non-HDL levels, and cardiovascular risk factors, such as blood pressure, BMI, diabetes, and smoking status.

It also examined how much one could lower risk if non-HDL cholesterol levels were a hypothetical 50% lower. Using this approach, the researchers saw the most significant reduction in risk in the youngest age group.

As an example, a male under 45 years of age has starting levels of non-HDL cholesterol of between 3.7–4.8 mmol per liter and at least two risk factors for cardiovascular disease; if the individual was to halve their levels of non-HDL cholesterol, they could reduce the risk from 16% to 4%.

A female with the same factors could reduce their risk from around 29% to 6%.

Using the same levels of non-HDL cholesterol in individuals of 60 years or more, males could reduce risk from 21% to 10%, and females from 12% to 6%.

The researchers suggest that intensive efforts to lower non-HDL cholesterol levels could reverse early signs of blocked arteries, which is known as atherosclerosis.

However, there was no clarity on how much slightly increased or seemingly normal cholesterol levels affected cardiovascular risk over a person's lifetime or at what level treatment recommendations should occur, especially in younger adults.

"Our estimates suggest that halving non-HDL cholesterol levels may be associated with reduced risk of cardiovascular events by the age of 75 years and that this reduction in risk is larger the sooner cholesterol levels are reduced."

Co-author Prof. Stefan Blankenberg

"The risk scores currently used in the clinic to decide whether a person should have lipid-lowering treatment only assess the risk of cardiovascular disease over 10 years, and so may underestimate lifetime risk, particularly in young people," notes the study's co-author, Prof. Stefan Blankenberg.

The authors say future research is needed to understand whether early intervention in younger people with low 10-year risk but high lifetime risk would have more benefits than later intervention.

A limitation of the study is that it may not apply to all regions or ethnic groups because its focus was on high income countries.

High cholesterol has no symptoms, and many people are unaware that they have high levels; however, doctors can check levels with a simple blood test.

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Medical News Today: Mindfulness training may lower blood pressure

Long believed to be a calming activity, a new study provides evidence of the benefits of mindfulness in reducing high blood pressure.

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A recent study uses mindfulness to address hypertension.

There is anecdotal evidence that meditation and mindfulness training may be able to reduce high blood pressure and hypertension. However, clinical confirmation of these claims has been scarce until last month, when researchers published a new study in the journal PLOS One.

The authors report the results of a Mindfulness-Based Blood Pressure Reduction (MB-BP) program specifically designed to "evaluate acceptability, feasibility, and effects on hypothesized proximal self-regulation mechanisms."

Participants who enrolled in the MB-BP program experienced significant reductions in blood pressure levels that were still in effect at follow-up examinations 1 year after the trial.

Hypertension is a significant risk factor for heart disease, which is the leading cause of death in the United States and globally. However, doctors can find hypertension challenging to treat.

"We know enough about hypertension that we can theoretically control it in everybody — yet in about half of all people diagnosed, it is still out of control," according to lead author Eric Loucks, associate professor of epidemiology, behavioral and social sciences, and medicine at Brown University in Providence, RI.

The blood pressure challenge and MB-BP

When doctors diagnose someone with high blood pressure, they typically recommend more healthful eating, which includes reducing salt intake, as well as regular exercise and weight loss. However, some people may find such permanent lifestyle changes difficult to maintain. Doctors might also prescribe medication to help control blood pressure.

In some people, hypertension has a genetic component, and lifestyle changes do not bring blood pressure down into the normal range.

The MP-BP curriculum incorporates mindfulness to address high blood pressure directly and to help people strengthen their ability to maintain the healthful habits that can keep it under control.

Loucks and his colleagues developed a 10-session program that followed 43 participants with high or elevated blood pressure for 1 year. More than 80% of participants had hypertension, with blood pressure readings of 130 millimeters of mercury (mmHg) systolic over 85 mmHg diastolic or higher. The other people had systolic readings of between 120 mmHg and 130 mmHg, with a diastolic measurement of at least 80 mmHg.

According to Loucks, the program was "a deliberately multimodal intervention" that taught participants a variety of techniques. These included mindfulness training and explanations of how behaviors can contribute to high blood pressure. They also encouraged the participants to take medications as prescribed by their doctors consistently.

The effect of the MB-BP curriculum

After 1 year, the participants' blood pressure was still lower than at baseline. In addition, their self-management skills remained strong. Participants who had struggled to follow healthful lifestyle recommendations before the study had maintained lifestyle changes.

The participants who benefited most from the program were those with stage 2 uncontrolled hypertension, which is characterized by a systolic measurement of over 140 mmHg. These participants saw a mean reduction in their blood pressure of 15.1 mmHg.

Additional testing is now underway through a randomized control trial involving a larger cohort of 200 participants. "Future trials," Loucks says, "could involve a dismantling study, where we would take out some of the health education, for example, and see if mindfulness training still had significant effects. That's certainly something we're looking at doing in the long-term. But mindfulness training is usually designed to be integrated with standard medical care."

Loucks is hopeful that the study's results can change lives: "I hope that these projects will lead to a paradigm shift in terms of the treatment options for people with high blood pressure."

"The hope is that if we can start mindfulness training early in life, we can promote a trajectory of healthy aging across the rest of people's lives. That will reduce their chances of getting high blood pressure in the first place."

Eric Loucks

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Medical News Today: Intermittent fasting can help ease metabolic syndrome

For those with metabolic syndrome, the necessary lifestyle and weight changes can be challenging. Now, a study has shown that eating within a certain time window can help tackle that.

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New research shows how intermittent fasting can help ease metabolic syndrome.

Metabolic syndrome is an umbrella term for a number of risk factors for serious conditions, such as diabetes, heart disease, and stroke. These risk factors include obesity and high blood pressure, among others.

This is no small issue in the United States, where one-third of adults have metabolic syndrome. In fact, the condition affects around 50% of people aged 60 and over.

Obesity is also prevalent, affecting around 39.8% of adults in the U.S. Obesity is closely linked to metabolic syndrome.

Receiving a diagnosis of metabolic syndrome offers a critical window of opportunity for making committed lifestyle changes before conditions such as diabetes set in.

However, making the necessary long-term lifestyle changes to improve one's health outlook is not always easy. Such changes include losing weight, managing stress, being as active as possible, and quitting smoking.

For the first time, a new study has looked into time-restricted eating, or intermittent fasting, as a means of losing weight and managing blood sugar and blood pressure for people with metabolic syndrome.

This new study, which appears in the journal Cell Metabolism, is set apart from previous studies that looked at the health and weight loss benefits of time-restricted eating in mice and healthy people.

"[People] who have metabolic syndrome/prediabetes are often told to make lifestyle interventions to prevent progression of their risk factors to […] disease," said co-corresponding study author Dr. Pam Taub, of the University of California San Diego School of Medicine.

"These [people] are at a crucial tipping point, where their disease process can be reversed."

"However, many of these lifestyle changes are difficult to make. We saw there was an unmet need in [people] with metabolic syndrome to come up with lifestyle strategies that could be easily implemented."

Clinical testing of time-restricted eating

Armed with the knowledge that time-restricted eating and intermittent fasting had been effective in treating and reversing metabolic syndrome in mice, the researchers set out to test these findings in a clinical setting.

"There are a lot of claims in the lay press about promising lifestyle strategies that have no data to back up the claims. We wanted to study [time-restricted eating] in a rigorous, well-designed clinical trial," said Dr. Taub.

Participants could eat what they wanted, when they wanted, within 10-hour windows.

The good news for the 19 participants with metabolic syndrome was that they could decide how much to eat and when they ate, as long as they restricted their eating to a window of 10 hours or less.

A 10-hour window had been effective with mice, and it offered people enough leeway that would be easy to comply with long-term.

"The participants in the study had control of their eating window," said Dr. Taub. "They could determine which 10-hour period they wanted to consume calories. They also had flexibility in adjusting their eating window by a couple [of] hours based on their schedule."

"Overall, participants felt they could adhere to this eating window. We did not restrict how many calories they consumed during their eating window," Dr. Taub told Medical News Today.

Most of the participants had obesity, and 84% were taking at least one medication, such as an antihypertensive drug or a statin.

Metabolic syndrome is associated with at least three of the following: high blood pressure, high fasting blood sugar, high triglyceride (body fat) levels, low high-density lipoprotein, or "good," cholesterol, and abdominal obesity.

Weight loss and better sleep

"As they started to adhere to this eating window, they started feeling better with more energy and better sleep, and this was positive reinforcement for them to continue with this 10-hour eating window," said Dr. Taub.

Almost all the participants ate breakfast later (around 2 hours after waking) and dinner earlier (around 3 hours before bed).

The study lasted for 3 months, during which time the participants showed a 3% weight and body mass index (BMI) reduction, on average, and a 3% loss of abdominal, or visceral, fat.

"All of these improvements reduce their risk of cardiovascular disease," said Dr. Taub.

Also, many participants showed a reduction in blood pressure and cholesterol, as well as improvements in fasting glucose. They also reported having more energy, and 70% reported an increase in the amount of time they slept or experienced sleep satisfaction.

The participants said that the plan was easier to follow than counting calories or exercising, and more than two-thirds kept it up for around a year after the study ended.

Dr. Taub recommends that anyone interested in trying time-restricted eating speak to their healthcare provider first, especially if they have metabolic syndrome and are taking medication, as weight loss may mean that medications require adjustment.

Original Article

Medical News Today: Passing kidney stones: 2-drug combo may relieve pain

Researchers from the Massachusetts Institute of Technology (MIT), in Cambridge, may have found a combination of drugs that can relieve the pain of passing a kidney stone. They performed their study in pigs.

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New research may help alleviate kidney stone pain.

Anyone who has ever passed a kidney stone knows that it can be a painful experience.
Every year, over half a million people in the United States experience this pain, and about 1 in 10 people will have a kidney stone at some point.
Kidney stones usually leave the body without a doctor's intervention, but this can be a slow, painful process.

However, the experience may soon be a thing of the past, according to a new study appearing in Nature Biomedical Engineering.

The team behind this research has found a combination of two drugs that can relax the walls of porcine ureters. Potentially, these medications could prevent kidney stones from causing such severe pain in humans.

The problem with kidney stones

Prof. Michael Cima, the study's senior author, notes, "We think this could significantly impact kidney stone disease, which affects millions of people."
Prof. Cima works with MIT's Department of Materials Science and Engineering and the school's Koch Institute for Integrative Cancer Research.

The stones form when urine that usually washes crystals from the kidneys contains too much solid waste and not enough liquid to get the job done.

These crystals clump together, forming stones that painfully force their way down the narrow ureter, causing cramps and inflammation. Most pass within a few weeks, though the discomfort can be consistent and severe. Occasionally, large stones require surgical removal.

Because the Food and Drug Administration (FDA) have yet to approve the use of any oral medications to widen the ureter and help the stones pass, doctors often simply prescribe pain relief medications.

Previously, other researchers have trialed ureter relaxants, but the drugs have not proved conclusively helpful.

About the new study

The study's lead author is Christopher Lee, Ph.D., of the Harvard-MIT Health Sciences and Technology joint department. He describes the motivation for the new research:

"If you look at how kidney stones are treated today, it hasn't really changed since about 1980, and there's a pretty substantial amount of evidence that the drugs given don't work very well. The volume of how many people this could potentially help is really exciting."

Christopher Lee, Ph.D.

Prof. Cima and Dr. Brian Eisner — the latter a study co-author and urologist that specializes in kidney stones — became interested in finding an effective approach. Lee soon joined their inquiry.

They began by identifying 18 drugs that doctors typically use to treat issues such as hypertension and glaucoma.

Since they suspected that medications directly administered to the ureter might be more effective, they exposed human ureteral cells, grown in lab dishes, to the 18 drug candidates in order to determine the extent to which the medications could relax ureteral tissue.

However, reports Prof. Cima, "We found several drugs that had the effect that we expected, and in every case, we found that the concentrations required to be effective were more than would be safe if given systemically."

2 drugs are better than one

The researchers further analyzed their results, looking for a two-drug combination that might be effective at lower, safer dosages. Eventually, they found two top-performing drugs that could produce even more positive results when administered together.

One of the drugs, nifedipine, is a calcium channel blocker that doctors can use to treat high blood pressure. The other is a Rho kinase inhibitor, which can treat glaucoma.

The team then delivered various dosages of the mixture via a tubular tool called a cystoscope to ureters that had been removed from pigs.

To gauge their effectiveness at relaxing the ureter tissue, the researchers tracked the frequency and length of contractions, or cramps, associated with passing the stones.

Later tests in live, sedated pigs revealed that the drug combination could nearly eliminate these contractions.

In addition, subsequent tests found no traces of either drug in the bloodstream. The implication is that this medication remains in the ureter, reducing the risk of systemic side effects.

The researchers hope to conduct further research and development, eventually leading to trials in humans.

Original Article

Medical News Today: A key area of the brain is smaller in women on the pill

At the base of the brain is a small but crucial area that acts as a control hub for the nervous and hormonal systems. Now, a study has found that among women, it is significantly smaller in those using birth control pills.

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New research finds an intriguing link between birth control pills and the size of a brain area key for managing the hormonal system.

The Food and Drug Administration (FDA) first approved birth control pills for use in the United States in 1960. Today, in the U.S., 12.6% of women between the ages of 15 and 49 years take these pills.

Known simply as "the pill," this oral contraceptive is one of the most popular forms of birth control, but people also use it to help with a wide range of conditions, including irregular menstruation, acne, polycystic ovary syndrome, endometriosis, and cramps.

In essence, the pill began as a way of preventing pregnancy using hormone control.

Originally, manufacturers engineered it to stop ovulation through the hormone progesterone, but it has since evolved to include a myriad of different types. These involve various hormone combinations, doses, and schedules, depending on the desired outcome. People can also use the pill to skip menstruation or stop it entirely.

But what does this harnessing of hormone power mean for the body's natural system of hormones?

Before the current study, which the researchers presented at the 2019 annual meeting of the Radiological Society of North America, there was very little research into the effects of birth control pills on the hypothalamus.

This small region of the brain, which sits above the pituitary gland at the organ's base, performs the vital role of producing hormones and helping control a range of bodily functions — including sleep cycles, mood, sex drive, appetite, body temperature, and heart rate.

The researchers who presented the study acknowledged that before their work, there had not been any reporting on the effect of birth control pills on the structure of the human hypothalamus.

"There is a lack of research on the effects of oral contraceptives on this small but essential part of the living human brain," says Michael Lipton, Ph.D., who is a professor of radiology at the Gruss Magnetic Resonance Research Center at Albert Einstein College of Medicine and medical director of MRI Services at the Montefiore Medical Center, both in New York City, NY.

This may be down to the fact that, until now, there was no known way of quantitatively analyzing MRI exams of the hypothalamus.

Lipton explained to Medical News Today that the team's previous work also inspired them to investigate these effects. "We have reported some quite interesting findings on sex-based risk in brain injury," he said. "Specifically, women seem to fare worse than men. Other studies have shown that the female sex hormone progesterone is neuroprotective."

"Since [oral contraceptive pills] are widely used, we wanted to explore the effects of [oral contraceptive pills] in healthy women to understand their potential role in our sex-divergent findings. The finding we report here is one outcome from that exploration."

Dramatic difference in hypothalamus size

"I was not expecting to see such a clear and robust effect," said Lipton. The researcher also notes, "We found a dramatic difference in the size of the brain structures between women who were taking oral contraceptives and those who were not."

For the study, the researchers recruited 50 women in good health, 21 of whom were taking birth control pills.

The team carried out MRI scans, which use radiology to generate images of organs, to look at the brain of each of the 50 women. They then used a validated methodology to gauge the hypothalamic volume.

"We validated methods for assessing the volume of the hypothalamus and confirm, for the first time, that current oral contraceptive pill usage is associated with smaller hypothalamic volume," says Lipton.

The researchers found that the women taking birth control pills had a significantly lower hypothalamus volume than those who were not using oral contraceptives.

Hypothalamic volume and anger

Although the study found that there was no noteworthy link between hypothalamic volume and a woman's cognitive ability, or ability to think, the preliminary findings suggest that there is an association between smaller hypothalamic volume and reduced anger.

"These findings are generally consistent with previous studies of [oral contraceptive pills] that support [an effect] on mood regulation. Our finding might represent a manifestation of the mechanism behind these effects or simply be unrelated. It is just too soon to tell," said Lipton.

"This initial study shows a strong association and should motivate further investigation into the effects of oral contraceptives on brain structure and their potential impact on brain function," concludes Lipton.

Regarding plans for future work, Lipton said: "For my group, the most important and immediate goal is to incorporate the role of [oral contraceptive pills] into our ongoing studies and to further explore the role of normal sex hormone cycles related to the menstrual cycle, as well as the role of androgens (testosterone) in men and women."

Original Article

Medical News Today: High blood pressure research: 2019 overview

In this special feature, we collate some of the most intriguing hypertension studies from 2019. We particularly focus on nutrition, risk factors, and hypertension's relationship with dementia.

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2019 has been a fascinating year for hypertension research.

Today, in the United States, around 1 in 3 adults has high blood pressure, which doctors also call hypertension.

Hypertension increases the risk of cardiovascular events, such as stroke and coronary disease, and, if doctors don't treat it, it can reduce lifespan.

Because it is worryingly prevalent, and because the physical ramifications can be significant, scientists are plowing a great deal of effort into understanding hypertension.

Although people first identified hypertension as a medical condition thousands of years ago, scientists are still picking away at the details.

Research that scientists completed in 2019 has thrown out some exciting and, in some cases, unexpected findings. For instance, a paper appearing in February concluded that, for women over 80 years of age, having "normal" blood pressure had an increased risk of mortality when compared with individuals with high blood pressure.

Elsewhere, Greek scientists concluded that napping might help reduce blood pressure. "Midday sleep appears to lower blood pressure levels at the same magnitude as other lifestyle changes," explains one of the researchers, Dr. Manolis Kallistratos.

Another surprising study, which scientists presented at the 83rd Annual Scientific Meeting of the Japanese Circulation Society, concluded that needing to urinate multiple times at night might be a sign of hypertension.

The role of nutrition

The food that we eat has a huge impact on our overall health; that goes without saying. The America Heart Association, for instance, suggest that eating a diet rich in fruits and vegetables and avoiding products with high levels of salt and fat can help keep blood pressure in check.

Over the past few years, interest in nutrition, in general, has skyrocketed. More and more, scientists are focusing on individual foods or food compounds that can directly benefit health. So, although poor diet is a well-known risk factor for hypertension, researchers in 2019 drilled down deeper.

Specific foods and supplements

One study appearing in 2019 investigated the impact of consuming walnuts on blood pressure. It concluded that the individuals who ate an experimental walnut-heavy diet experienced a significant reduction in blood pressure.

In these types of studies, it is worth digging a little deeper; often, industry or organizations who might stand to benefit from positive results are funding them. The walnut study above, for instance, was partly funded by the California Walnut Commission.

This observation does not mean that we should dismiss the results out of hand, but it provides pause for thought.

Another recent study concentrated on spirulina, which is the dried biomass of a bacterium called Spirulina platensis. Manufacturers can add it to foods, and some people take it as a supplement.

Earlier experiments hinted at spirulina's potential to reduce hypertension, and in the most recent study, they attempted to find out why this might be.

The scientists concluded that a protein that the digestion of spirulina produces causes blood vessels to relax. The authors hope that this protein, known as SP6, might one day be useful in the treatment of hypertension.

Preservatives, additives, and water

Rather than focus on specific foods, a further study looked at the impact of buying food from local retailers rather than supermarkets.

The authors theorized that by eating local produce, individuals would avoid consuming the various preservatives and additives that keep food "fresh" over long distances.

Although the study was relatively small, the authors found that after 6 months, those who consumed local produce had lower levels of visceral fat, improved depression scores, and reduced systolic blood pressure.

Approaching from a different angle, a team of scientists recently asked whether drinking water that is high in minerals might reduce blood pressure.

To investigate, they focused on people living in a coastal region of Bangladesh. Drinking water there varies in salinity. In areas of high salinity, the water contains greater quantities of sodium, which we know increases blood pressure. However, the same water also includes more magnesium and calcium, both of which reduce blood pressure.

The authors concluded that higher salinity levels decreased blood pressure overall; they write that "the [blood pressure]-lowering effects of [calcium] and [magnesium] counteracted the harmful effects of [sodium].

Causes and risk factors

Some risk factors for hypertension are fairly well established; they include drinking excessive amounts of alcohol, smoking tobacco, stress, and obesity. However, because high blood pressure is so common, there are likely to be many more factors at play.

Similarly, although scientists know which lifestyle and dietary factors influence blood pressure, they are not entirely sure how they cause the changes.

Understanding why and how blood pressure arises in some people and not others is essential and could, potentially, lead to innovative ways of treating or preventing hypertension.

Some scientists are exploring possible risk factors which, at face value, seem unlikely. For instance, one paper, appearing in the Journal of Public Health in June, examined the role of where people live.

Earlier studies found an association between exposure to air pollution and hypertension risk, and this latest work confirms those earlier suspicions and takes it a step further.

As expected, the researchers found a relationship between air pollution and hypertension; however, the increase in risk was only significant for those who were living in multi-family homes, such as blocks of flats.

The authors believe that this might be due to several factors, for instance, living in close quarters with other people may be more stressful or more noisy. This study provides a glimpse of the complex realm of potential elements that might influence blood pressure.

Oral hygiene

Bizarrely, one group of scientists recently investigated how mouthwash might influence hypertension risk.

Publishing their findings in the journal Frontiers in Cellular and Infection Microbiology, the authors conclude that mouthwash kills "good bacteria" in the mouth. These good bacteria produce nitric oxide (NO), which is important for blood vessel health.

NO acts as a vasodilator, which means it causes the muscles that line blood vessels to relax, thereby widening the vessels and reducing blood pressure.

In particular, the scientists concentrated on the chemical chlorhexidine, which they found in some mouthwashes.

According to the authors, they demonstrated that "twice-daily chlorhexidine usage was associated with a significant increase in systolic blood pressure after 1 week of use, and recovery from use resulted in an enrichment in nitrate-reducing bacteria on the tongue."

Still focusing on the oral region, a 2019 review looked for links between gum disease and hypertension. They showed that individuals with severe periodontitis — a form of gum disease — had a 49% increased risk of hypertension.

Senior author Prof. Francesco D'Aiuto explains their results in a nutshell: "We observed a linear association — the more severe periodontitis is, the higher the probability of hypertension."

The role of zinc

Another project investigated the role of zinc in maintaining blood pressure at healthy levels. Over the years, researchers have noted links between low zinc levels and an increased risk of high blood pressure, but the precise mechanism has been tough to pin down.

The latest research identified the key player in this interaction between zinc and blood pressure; according to the authors, the sodium chloride cotransporter (NCC) in the kidney is the lynchpin. The NCC is responsible for pumping sodium back into the body, thereby preventing it from being excreted in the urine.

Zinc interacts with the NCC: when zinc is present, the NCC is less active, meaning that the body retains less sodium. This is important because high sodium levels — from consuming too much salt, for instance — are factors in increasing the risk of hypertension.

The authors hope that this new knowledge will help improve treatment and write:

"Understanding the specific mechanisms by which [zinc deficiency] contributes to [blood pressure] dysregulation may have an important effect on the treatment of hypertension in chronic disease settings."

Hypertension and dementia

Scientists have identified a relationship between hypertension and vascular dementia. The association makes sense because vascular dementia can occur following stroke, and hypertension is a risk factor for stroke.

However, it also appears that hypertension might increase the risk of other types of dementia, including Alzheimer's disease.

A study appearing in June this year found that a common blood pressure drug — nilvadipine — slowed the progress of Alzheimer's disease by improving blood flow in the brain.

Specifically, the research team showed that people who took the medication had a 20% increase in blood flow in the hippocampus, a brain region vital for memory and learning, in comparison to those who did not take nilvadipine.

Patterns throughout life

Other scientists have looked at fluctuations in blood pressure and their possible role in dementia. For instance, one investigation that recruited participants who were living with Alzheimer's disease found that the condition progressed quicker in those whose blood pressure fluctuated most.

"More fluctuations [in blood pressure] might affect whether cognitive function declines more slowly or rapidly."

Senior author Dr. Jurgen Claassen

With a similar theme, another group of scientists observed the pattern of blood pressure across decades. The authors summarize their findings:

"[A] pattern of sustained hypertension from middle to late life and a pattern of midlife hypertension followed by late-life hypotension were associated with an increased risk for subsequent dementia, compared with participants who maintained normal blood pressure."

Another project that charted hypertension over a lifespan found that individuals with high or rising blood pressure between 36 and 53 years of age were more likely to have white matter lesions and a smaller brain volume in later life.

The authors hope that these findings will inspire both doctors and the public to check and take charge of their blood pressure sooner rather than later.

As 2020 rolls into view, hypertension is sure to stay high on the medical research agenda. As science gradually untangles hypertension's causes and mechanisms, managing and minimizing this highly prevalent condition must draw ever closer.

Original Article