Body

In salt-sensitive hypertension, immune cells gather in the kidneys and shoot out free radicals, heightening blood pressure and damaging this pair of vital organs, scientists report.

These highly reactive chemicals, also called reactive oxygen species, or ROS, are a byproduct of our body's use of oxygen that our immune system uses to kill invaders. But at high levels, they also are known to alter key components of our body like proteins, and contribute to a myriad of diseases from hypertension to cancer.

"It's a beneficial mechanism of our immune system except when it becomes chronic and uncontrolled," says Dr. Justine M. Abais-Battad, physiologist in the Department of Physiology at the Medical College of Georgia at Augusta University and corresponding author of the study in the journal Free Radical Biology and Medicine.

In salt-sensitive hypertension, it becomes what physiology chair Dr. David L. Mattson terms an "inappropriate" immune response, producing excessive ROS, increasing inflammation and blood pressure and causing the kidneys to hold onto more salt.

"That is what we think is the problem," says Mattson, Georgia Research Alliance Eminent Scholar in Hypertension and senior study author.

For their studies, the scientists used an established animal model for salt sensitivity, the Dahl SS rat. They also have a version of that rat that lacks NADPH oxidase bodywide, an enzyme complex and major producer of ROS that's elevated in the kidneys of salt-sensitive rats. The rat missing NAPDH oxidase is protected from hypertension and kidney damage on a high-salt diet, another clue that ROS is a big factor in hypertension, Abais-Battad says.

To pinpoint the source of the ROS cells, they restored the ability of that NADPH oxidase knockout rat to make the ROS-producing enzyme but only in immune cells. All cells can make ROS but they suspected the immune cells were the troublemakers here.

In the face of a high-salt diet, these rats' protection was lost, their blood pressure went up and they experienced kidney damage. When taken off the high-salt diet, those problems essentially resolved.

"ROS specifically produced by the immune cells is enough to give these rats hypertension," says Abais-Battad. "That is a big problem," says Mattson, but it points to a clear potential treatment target.

"If we can begin to understand an approach where we could block this production of free radicals by those cells particularly in the kidney, there is a potential treatment," he says.

While antioxidant therapies have failed for many maladies, Mattson says location is likely one reason. "They are just not getting to the right places," he says. Knowing the cellular source of the ROS is important for designing effective therapies that will.

"Our study shows that ROS from immune cells causes salt-sensitive hypertension, and that targeted antioxidant therapies may be necessary to produce maximal beneficial and protective effects," they write.

Mattson's lab and others have linked hypertension with the immune system and increased immune cells in the kidneys. In salt-sensitive hypertension, the scientists have watched immune cells congregate around the kidneys' submicroscopic blood vessels -- already under super high pressure as part of their endless role of filtering blood -- and exacerbate pressure and kidney damage.

"They are sort of living on the edge anyway," says Mattson. This damage ultimately shows up as protein in the urine, an indicator of the problem, Abais-Battad says.

A high-salt diet fed to normal rats doesn't cause hypertension or that clustering of immune cells. Postmortem studies of humans who died from all causes indicated those with hypertension also had more immune cells in their kidneys along with increased kidney damage.

Now they are working to learn more about precisely what the free radicals the immune cells produce are doing and they think its several bad things

For this study, the scientists wanted to know why the immune cells move into the kidneys and what they are doing when they get there. Based on what they and others already had seen, they reasoned they could be producing ROS.

In terms of the true instigator, some theorize an errant immune system also is the culprit, driving up pressure a bit initially, and causing damage that attracts the army of ROS-producing immune cells. Mattson's lab theorizes and has evidence that the problem actually starts with kidneys that do not eliminate salt sufficiently, which means fluid levels increase and so does pressure.

While it may be sound advice for all of us to lighten up on the salt, our kidneys will eliminate excess salt for most us. But in about half of people with hypertension, salt is a major driver and there are not currently tests to easily diagnose it or drugs that target this pervasive problem, Mattson says.

"All of us have all kinds of salts in our body and we need it to hold onto water, "Mattson says. "It's only in maybe the last 50 years or so when we adapted to this Western, modern lifestyle where we are consuming excess salt that this becomes a problem.

"With a little bit of a pressure increase, you can go on a low-salt diet or eat more potassium or fresh vegetables, and probably bring your blood pressure down," Mattson adds. "But if you have your immune system fully activated, the disease is amplified and I think that is where we get into trouble."

There are a lot of high-salt culprits besides French fries, like frozen dinners and prepackaged foods, canned vegetables, packaged deli meat even some of our favorite condiments like ketchup. So while a low-salt diet may be helpful, it also may be harder than you think, they say.

There is evidence that suppressing the immune system can lower blood pressure but the scientists say that likely is not a smart or safe way to tackle the problem.

While they are working on both a test and targeted therapies for salt-sensitive hypertension, right now, determining salt sensitivity is essentially anecdotal when, in first steps to lower blood pressure, people find that dietary modifications, like eating less canned and processed foods, really start to work. “If you change your dietary habits and blood pressure comes down that would be a clue you have salt-sensitive hypertension,” Mattson says.

The scientists also note that as with many diseases, there are both genetic and environmental factors that contribute to hypertension.

Our fist-sized kidneys filter about a half cup of blood every minute, and are critical to maintaining a healthy fluid balance in the body, a blood pressure that ensures adequate blood and oxygen delivery bodywide, and eliminating things we don't need like excessive salt, while resorbing things we do.

About 46% of white adults and 54% of black adults have high blood pressure, according to the Centers for Disease Control and Prevention, and an estimated 1 in 5 adults are unaware they have it. Among those recommended to take medication, about 32% of white and 25% of black adults have control.

"If you just walk outside, you will see somebody who has this going on inside," Mattson says of the pervasive health problem. "It shortens their life."

In the study, 85% (99/116) of children with life-threatening autoimmune conditions had complete or near complete recovery after biomarker was spotted and they were subsequently given appropriate treatment

A group of life-threatening neurological conditions affecting children have been linked to an antibody which points to potential treatment, according to an observational multicentre study involving 535 children with central nervous system (CNS) demyelinating disorders and encephalitis, published in The Lancet Neurology journal.

The findings suggest that the myelin oligodendrocyte glycoprotein (MOG) antibody is associated with a wider range of life-threatening autoimmune conditions than previously thought, including neuromyelitis optica spectrum disorders and encephalitis, which cause severe neurological (brain and nervous system) symptoms such as vision loss, muscle weakness, and loss of coordination and speech.

Because this group of CNS disorders can mimic similar conditions like multiple sclerosis (MS), they are difficult to diagnose correctly. Until around 10 years ago, patients with these demyelinating diseases were considered to have atypical forms of MS, and the prognosis and best treatment options were unknown. Over the last 10 years, multiple studies have shown that several demyelinating diseases (including optic neuritis, myelitis, and acute disseminated encephalomyelitis [ADEM]) associate with the MOG-antibody biomarker, and patients affected by this group of diseases frequently improve with immunotherapy. However, the best treatment approach and long-term outcome remain unknown. Now, this new study suggests that testing for the biomarker could speed accurate diagnosis and help identify the appropriate treatment for some of these disorders.

In the study, 85% (99/116) children who tested positive for MOG antibodies and given appropriate treatment had complete or near complete recovery, but 15% (17) experienced moderate to severe disease-related deficits not caused by the treatment (eg, cognitive impairment, epilepsy, vision loss), and one died from their disease.

"The diagnosis of many of these patients especially those with encephalitis would have been missed if it were not for the prospective design our study," says Dr Thais Armangue from the Sant Joan de Deu Children's Hospital, University of Barcelona, in Spain who co-led the research. "Identifying these patients is important because most of the children who tested positive for MOG antibodies responded to treatment with immunotherapy." [1]

Co-lead author Professor Josep Dalmau from the University of Barcelona explains, "Demyelinating diseases in children can be very difficult to distinguish because they present with similar symptoms and imaging features. Correct and early diagnosis allows for treatment with immunosuppressants, rather than the treatments specifically used in MS that are not effective in most of these diseases. Moreover, it is important to differentiate between those diseases that do not require chronic treatment and others in which prolonged immunotherapy is needed to improve long-term outcomes." [1]

MOG antibodies damage the protective covering (myelin sheath) that surrounds nerve fibres in the brain, optic nerves, and spinal cord, so messages cannot pass along these nerves effectively, causing symptoms such as vision loss, muscle weakness, and pain. Many children may only experience one MOG antibody disease event, and have no further symptoms. However, some children may be at risk of further relapses months, sometimes years, later.

Although there is increasing recognition of MOG-antibody associated syndromes in children, the full range of diseases associated with MOG antibodies remains unknown.

To provide more evidence, researchers conducted a prospective study of children (median age 6 years) with suspected demyelinating syndromes (239 children) and encephalitis other than ADEM (296) attending 40 hospitals across Spain between June 1, 2013, and December 31, 2018. Participants who tested positive for MOG antibodies were assessed for clinical features, response to treatment (ie, number of relapses), and outcomes over a median follow-up of 42 months.

In total, 116 (22%) of 535 children were found to be positive for MOG antibodies, including 94 (39%) with demyelinating syndromes and 22 (7%) with autoimmune encephalitis. Importantly, 24% (28/116) of these children had syndromes not previously associated with MOG antibodies.

Among the 64 patients with autoimmune encephalitis, MOG antibodies were the most frequent biomarkers--more common than all other neuronal antibodies combined (22 [34%] vs 21 [33%])--suggesting that MOG antibody testing should be conducted when diagnosing children with suspected encephalitis after excluding infectious causes, particularly as these patients often respond to treatment with immunotherapy.

The findings also suggest that younger children with MOG-antibody associated syndromes tend to present with clinical features of ADEM (which is an inflammatory condition that mainly affects the brain), whilst older children are more likely to have signs of optic neuritis (eg, loss of vision, pain in the eye) or myelitis (eg, back pain, weakness in both legs).

During follow-up, 33 (28%) of 116 patients positive for MOG antibody disease had relapses. Most of these patients (99/116, 85%) recovered well. However, 17 (15%) experienced disease-related moderate to severe deficits, and one died due to their disease.

"Despite advances in diagnostic testing for encephalitis, up to half of cases have no clear cause. Our findings reveal that the spectrum of MOG antibody disease is broader than previously thought and includes autoimmune encephalitis as well as multiple demyelinating syndromes", says co-author Dr Gemma Olive-Cirera from the Sant Joan de Deu Children's Hospital, University of Barcelona, Spain. "In light of our findings, current classifications and terminology of MOG antibody-associated syndromes should be updated." [1]

The authors note several limitations, including that this was not a registry-based study, and therefore could not assess the incidence or prevalence of MOG antibody-associated syndromes, and that the follow-up was short, which could result in the frequency of relapses being underestimated.

Writing in a linked Comment, Dr Romain Marignier from the Hôpital Neurologique Pierre Wertheimer, France (who was not involved in the study) describes the research as "a milestone in the understanding of MOG antibody-associated syndromes", and writes: "In view of the very broad clinical spectrum now associated with MOG autoimmunity, the next challenge will be to identify the optimal therapeutic strategy for each clinical presentation. This objective is closely connected to a better understanding of the pathogenic role of MOG antibodies, and the need for early, robust, and specific prognostic factors of relapse and disability."

Boston, MA--Scaling up cervical cancer screening coverage in the U.S. to 90% could expedite elimination of the disease and avert more than 1,000 additional cases per year, according to a new study led by researchers from Harvard T.H. Chan School of Public Health. Their modeling study found that this would be the most effective way to speed up elimination, compared to current levels of screening and human papillomavirus (HPV) vaccination.

"Although HPV vaccination will be a major contributor to reducing cervical cancer over time, we found that in the immediate term, screening continues to play a critical role in reducing the burden of cervical cancer in U.S.," said Emily Burger, a research scientist in the Center for Health Decision Science at Harvard Chan School who co-led the study.

The study will be published online in The Lancet Public Health on February 10.

In 2018, the World Health Organization (WHO) issued a global call to eliminate cervical cancer as a public health problem, setting a disease target of four or fewer cases per 100,000 women. With vaccination against HPV, the virus known to cause cervical cancer, and early detection through screening, cervical cancer is one of the most preventable and treatable forms of cancer.

In the U.S., the HPV vaccine is recommended routinely for both girls and boys ages 11-12 years and up to age 26 years for catch-up vaccination. For the study, using current vaccine coverage rates and trends, the researchers estimated that 75% of girls would be vaccinated by age 26 and 62% of boys would be vaccinated by age 21.

Cervical cancer screening using Pap testing is recommended every three years for women ages 21-65 years, yet there is a large proportion of women who do not adhere to guidelines, either screening too much or too little; an estimated 14% of women are never screened.

This study is the first known comparative modeling analysis to project a timeframe for cervical cancer elimination in the U.S. The researchers used two independent disease modeling platforms (one from Harvard Chan School and one from Cancer Council New South Wales, Australia) to compare nine different HPV vaccination and cervical cancer screening interventions with a "status quo" scenario reflecting current screening and vaccination practices. They evaluated the potential for each scenario to achieve a threshold for cervical cancer elimination of four cases per 100,000 women, as well as a more ambitious threshold of one case per 100,000 women, over time.

They found that under the status quo scenario, cervical cancer elimination could be achieved by the years 2038-2046. Scaling up screening coverage to 90% expedited the timing of elimination by 10-13 years and averted an average of 1,400-2,088 additional cases per year. Increasing HPV vaccination coverage to 90% of girls and vaccinating adults of both sexes aged 26-45 years had almost no impact on elimination timing and minimal impacts on incidence.

This analysis is an extension of two studies published last week (see links below) evaluating the potential for and timing of cervical cancer elimination, as well as the mortality impacts of scaling up HPV vaccination, cervical cancer screening, and cancer treatment services in 78 low-income and lower-middle income countries. Those analyses, published in The Lancet, were co-led by three modeling groups comprising the WHO Cervical Cancer Elimination Modeling Consortium (CCEMC), which includes the authors of the current study.

"Across all three analyses, we were able to project the vast number of cervical cancer cases and deaths averted globally by ensuring high uptake of both prevention and treatment services for cervical cancer," said co-lead author Megan Smith, program manager at the Cancer Council New South Wales in Australia.

"Together with the WHO elimination initiative, we hope this analysis will galvanize public health efforts to improve access to both primary and secondary cervical cancer prevention in the U.S.," said senior author Jane Kim, professor of health decision science at Harvard Chan School.

A new study estimates that improving the rates of handwashing by travelers passing through just 10 of the world's leading airports could significantly reduce the spread of many infectious diseases. And the greater the improvement in people's handwashing habits at airports, the more dramatic the effect on slowing the disease, the researchers found.

The findings, which deal with infectious diseases in general including the flu, were published in late December, just before the recent coronavirus outbreak in Wuhan, China, but the study's authors say that its results would apply to any such disease and are relevant to the current outbreak.

The study, which is based on epidemiological modeling and data-based simulations, appears in the journal Risk Analysis. The authors are Professor Christos Nicolaides PhD '14 of the University of Cyprus, who is also a fellow at the MIT Sloan School of Management; Professor Ruben Juanes of MIT's Department of Civil and Environmental Engineering; and three others.

People can be surprisingly casual about washing their hands, even in crowded locations like airports where people from many different locations are touching surfaces such as chair armrests, check-in kiosks, security checkpoint trays, and restroom doorknobs and faucets. Based on data from previous research by groups including the American Society for Microbiology, the team estimates that on average, only about 20 percent of people in airports have clean hands -- meaning that they have been washed with soap and water, for at least 15 seconds, within the last hour or so. The other 80 percent are potentially contaminating everything they touch with whatever germs they may be carrying, Nicolaides says.

"Seventy percent of the people who go to the toilet wash their hands afterwards," Nicolaides says, about findings from a previous ASM study. "The other 30 percent don't. And of those that do, only 50 percent do it right." Others just rinse briefly in some water, rather than using soap and water and spending the recommended 15 to 20 seconds washing, he says. That figure, combined with estimates of exposure to the many potentially contaminated surfaces that people come into contact with in an airport, leads to the team's estimate that about 20 percent of travelers in an airport have clean hands.

Improving handwashing at all of the world's airports to triple that rate, so that 60 percent of travelers to have clean hands at any given time, would have the greatest impact, potentially slowing global disease spread by almost 70 percent, the researchers found. Deploying such measures at so many airports and reaching such a high level of compliance may be impractical, but the new study suggests that a significant reduction in disease spread could still be achieved by just picking the 10 most significant airports based on the initial location of a viral outbreak. Focusing handwashing messaging in those 10 airports could potentially slow the disease spread by as much as 37 percent, the researchers estimate.

They arrived at these estimates using detailed epidemiological simulations that involved data on worldwide flights including duration, distance, and interconnections; estimates of wait times at airports; and studies on typical rates of interactions of people with various elements of their surroundings and with other people.

Even small improvements in hygiene could make a noticeable dent. Increasing the prevalence of clean hands in all airports worldwide by just 10 percent, which the researchers think could potentially be accomplished through education, posters, public announcements, and perhaps improved access to handwashing facilities, could slow the global rate of the spread of a disease by about 24 percent, they found. Numerous studies (such as this one) have shown that such measures can increase rates of proper handwashing, Nicolaides says.

"Eliciting an increase in hand-hygiene is a challenge," he says, "but new approaches in education, awareness, and social-media nudges have proven to be effective in hand-washing engagement."

The researchers used data from previous studies on the effectiveness of handwashing in controlling transmission of disease, so Juanes says these data would have to be calibrated in the field to obtain refined estimates of the slow-down in spreading of a specific outbreak.

The findings are consistent with recommendations made by both the U.S. Centers for Disease Control and the World Health Organization. Both have indicated that hand hygiene is the most efficient and cost-effective way to control disease propagation. While both organizations say that other measures can also play a useful role in limiting disease spread, such as use of surgical face masks, airport closures, and travel restrictions, hand hygiene is still the first line of defense -- and an easy one for individuals to implement.

While the potential of better hand hygiene in controlling transmission of diseases between individuals has been extensively studied and proven, this study is one of the first to quantitatively assess the effectiveness of such measures as a way to mitigate the risk of a global epidemic or pandemic, the authors say.

The researchers identified 120 airports that are the most influential in spreading disease, and found that these are not necessarily the ones with the most overall traffic. For example, they cite the airports in Tokyo and Honolulu as having an outsized influence because of their locations. While they respectively rank 46th and 117th in terms of overall traffic, they can contribute significantly to the spread of disease because they have direct connections to some of the world's biggest airport hubs, they have long-range direct international flights, and they sit squarely between the global East and West.

For any given disease outbreak, identifying the 10 airports from this list that are the closest to the location of the outbreak, and focusing handwashing education at those 10 turned out to be the most effective way of limiting the disease spread, they found.

Nicolaides says that one important step that could be taken to improve handwashing rates and overall hygiene at airports would be to have handwashing sinks available at many more locations, especially outside of the restrooms where surfaces tend to be highly contaminated. In addition, more frequent cleaning of surfaces that are contacted by many people could be helpful.

Migraines affect not only adults but frequently also children and adolescents. Researchers from the University of Basel have concluded that in this age group, the preventive pharmacological treatment of migraine is no more effective than placebo in the long term. The results of the review, carried out as part of an international collaboration, have been published in the scientific journal JAMA Pediatrics.

Migraine not only affects the wellbeing of children and adolescents but also interferes with every area of their lives. In order to prevent migraine attacks and reduce symptoms, a variety of drugs are used in pharmacological migraine prophylaxis.

Until now, the treatment of young patients has largely been based on adult studies, but it is questionable whether these prophylactic interventions in children and adolescents have a comparable effect. Moreover, it is suspected that the placebo effect is often more pronounced in the younger age group.

Psychologists from the University of Basel have now taken part in an international collaboration to investigate which drugs are effective for migraine prophylaxis in children and adolescents. Previously, individual studies have compared one medication with another or with placebo. The aim of this systematic review was to summarize individual studies of this kind and to allow their comparison. Are the administered drugs more effective than placebos? And do any differences exist between these medications in terms of their efficacy and side-effects?

No long-term effects compared with placebo

As part of their network meta-analysis, the researchers analyzed 23 studies from the period between 1967 and 2018, with a total of more than 2,200 patients. Of these, about a quarter received placebo, while the remainder were treated with antiepileptics, antidepressants, calcium channel blockers, antihypertensive agents or food supplements.

The results show that relative to placebo, none of the tested medications could be demonstrated to have a significant long-term effect (five to six months or longer) on children and adolescents. Short-term improvements (less than five months) could only be identified for the active substances propranolol and topiramate.

"Our study therefore shows that the preventive pharmacological treatment of pediatric migraine with all these drugs is barely more effective than placebo," says Dr. Cosima Locher from the Faculty of Psychology at the University of Basel.

The results of this study highlight the need for further research into migraine prophylaxis in young patients in order to identify factors that are vital for the individual efficacy of these treatments. There is also a need for further research into the placebo effect specifically in children and adolescents.

The Basel researchers' initial results suggest that this could pave the way for innovative treatment methods, taking into account the expectations of patients and their relationships with the treatment provider. This could then enhance the clinical effect of medication or allow it to be achieved without the use of drugs, according to the researchers.

Researchers have discovered a neural signature that predicts whether individuals with depression are likely to benefit from sertraline, a commonly prescribed antidepressant medication. The findings, published in Nature Biotechnology, suggest that new machine learning techniques can identify complex patterns in a person's brain activity that correlate with meaningful clinical outcomes. The research was funded by the National Institute of Mental Health (NIMH), part of the National Institutes of Health.

"There is a great need in psychiatry today for objective tests that can inform treatment and go beyond some of the limitations of our diagnostic system. Our findings are exciting because they reflect progress made toward this clinical goal, and they also show the potential of bringing sophisticated data analytic methods to psychiatry," explained senior author Amit Etkin, M.D., Ph.D., a professor of psychiatry and behavioral sciences at Stanford University and CEO of Alto Neuroscience, Los Altos, California.

Major depression is one of the most common mental disorders, affecting about 7% of adults in the U.S. in 2017, but the symptoms experienced can vary from person to person. While some may experience many of the characteristic features--including persistent sad mood, feelings of hopelessness, loss of pleasure, and decreased energy--others may experience only a few. There are several evidence-based options available for treating depression, but determining which treatment is likely to work best for a specific person can be a matter of trial and error.

Previous research has suggested that specific components of brain activity, as measured by resting-state electroencephalography (EEG), could yield insight into how people will respond to certain treatments. However, researchers have yet to develop predictive models that can differentiate between response to antidepressant medication and response to placebo and that can also predict outcomes for individual patients. Both features are essential for the neural signature to have clinical relevance.

Etkin, co-senior author Madhukar H. Trivedi, M.D., a professor of psychiatry at the University of Texas Southwestern Medical Center, Dallas, and first author Wei Wu, Ph.D., an instructor at Stanford University, California, drew on insights from neuroscience, clinical science, and bioengineering to build an advanced predictive model. The researchers developed a new machine learning algorithm specialized for analyzing EEG data called SELSER (Sparse EEG Latent SpacE Regression). They hypothesized that this algorithm might be able to identify robust and reliable neural signatures of antidepressant treatment response.

The researchers used SELSER to analyze data from the NIMH-funded Establishing Moderators and Biosignatures of Antidepressant Response in Clinic Care (EMBARC) study, a large randomized clinical trial of the antidepressant medication sertraline, a widely available selective serotonin reuptake inhibitor (SSRI). As part of the study, participants with depression were randomly assigned to receive either sertraline or placebo for eight weeks. The researchers applied SELSER to participants' pre-treatment EEG data, examining whether the machine learning technique could produce a model that predicted participants' depressive symptoms after treatment.

SELSER was able to reliably predict individual patient response to sertraline based on a specific type of brain signal, known as alpha waves, recorded when participants had their eyes open. This EEG-based model outperformed conventional models that used either EEG data or other types of individual-level data, such as symptom severity and demographic characteristics. Analyses of independent data sets, using several complementary methods, suggested that the predictions made by SELSER may extend to broader clinical outcomes beyond sertraline response.

In one independent data set, the researchers found that the EEG-based SELSER model predicted greater improvement for participants who had shown partial response to at least one antidepressant medication compared with those who had not responded to two or more medications, in line with the patients' clinical outcomes. Another independent data set showed that participants who were predicted by SELSER to show little improvement with sertraline were more likely to respond to treatment involving a specific type of non-invasive brain stimulation called transcranial magnetic stimulation (in combination with psychotherapy).

Work is now underway to further replicate these findings in large, independent samples to determine the value of SELSER as a diagnostic tool. According to Etkin, Trivedi, Wu, and colleagues, the present research highlights the potential of machine learning for advancing a personalized approach to treatment in depression.

"While work remains before the findings in our study are ready for routine clinical use, the fact that EEG is a low-cost and accessible tool makes the translation from research to clinical practice more possible in the near term. I hope our findings are part of a tipping point in the field with respect to the impact of machine learning and objective testing," Etkin concluded.

DALLAS - Feb. 10, 2020 - Artificial intelligence may soon play a critical role in choosing which depression therapy is best for patients.

A national trial initiated by UT Southwestern in 2011 to better understand mood disorders has produced what scientists are calling the project's flagship finding: a computer that can accurately predict whether an antidepressant will work based on a patient's brain activity.

The new research is the latest among several studies from the trial that cumulatively show how high-tech strategies can help doctors objectively diagnose and prescribe depression treatments. Although implementing these approaches will take time, researchers predict tools such as AI, brain imaging, and blood tests will revolutionize the field of psychiatry in the coming years.

"These studies have been a bigger success than anyone on our team could have imagined," says Madhukar Trivedi, M.D., a UT Southwestern psychiatrist who oversaw the multi-site trial involving Stanford, Harvard and other institutions. "We provided abundant data to show we can move past the guessing game of choosing depression treatments and alter the mindset of how the disease should be diagnosed and treated."

EEG-based predictions

The study published in Nature Biotechnology included more than 300 participants with depression who were randomly chosen to receive either a placebo or an SSRI (selective serotonin reuptake inhibitor), the most common class of antidepressant. Researchers used an electroencephalogram, or EEG, to measure electrical activity in the participants' cortex before they began treatment. The team then developed a machine-learning algorithm to analyze and use the EEG data to predict which patients would benefit from the medication within two months.

Not only did the AI accurately predict outcomes, further research suggested that patients who were doubtful to respond to an antidepressant were likely to improve with other interventions such as psychotherapy or brain stimulation.

The findings were validated in three additional patient groups.

"This study takes previous research, showing that we can predict who benefits from an antidepressant, and actually brings it to the point of practical utility," says Amit Etkin, M.D., Ph.D., a Stanford University psychiatry professor who worked with Trivedi to develop the algorithm.

Among the next steps, researchers say, is developing an AI interface that can be widely integrated with EEGs across the country, as well as seeking approval from the U.S. Food and Drug Administration.

Signatures of depression

Data from the study derive from the 16-week EMBARC trial, which Trivedi initiated at four U.S. sites to establish biology-based, objective strategies to remedy mood disorders.

The project evaluated patients with major depressive disorder through brain imaging and various DNA, blood, and other tests. His goal was to address a troubling finding from another study he led (STAR*D) that found up to two-thirds of patients do not adequately respond to their first antidepressant.

"We went into this thinking, 'Wouldn't it be better to identify at the beginning of treatment which treatments would be best for which patients?'" Trivedi explains.

Previous EMBARC studies identified various predictive tests, including the use of magnetic resonance imaging (MRI) to examine brain activity in both a resting state and during the processing of emotions. EEG will likely be the most commonly used tool, Trivedi says, because it's less expensive and - in most cases - will be equally or more effective.

However, a blood test or MRI may be needed for some patients if the depression is manifesting itself in a different way.
"There are many signatures of depression in the body," Trivedi says. "Having all these tests available will improve the chances of choosing the right treatment the first time."

Growing problem

According to data from the National Health and Nutrition Examination Survey, antidepressant use in the U.S. has increased nearly 65% over a decade and a half - from 7.7% in 1999-2002 to 12.7% in 2011-2014. Trivedi says the expanded use of medications make it more critical to further understand the underpinnings of depression and ensure patients are prescribed an effective therapy.

While his team continues to evaluate data from the EMBARC trial, Trivedi has initiated other large research projects to help improve the remission rate of depression. Among them is D2K, a study that will enroll 2,500 patients with depression and bipolar disorders and follow them for 20 years. In addition, RAD is a 10-year study of 2,500 participants (ages 10-24) that will uncover factors for reducing the risk of developing mood or anxiety disorders.

Utilizing some of these enrollees, Trivedi's research team will study the results from several other tests to assess patients' biological signatures to determine the most effective treatment.

"It can be devastating for a patient when an antidepressant doesn't work," Trivedi says. "Our research is showing that they no longer have to endure the painful process of trial and error."

A new method of interpreting brain activity could be used in clinics to help determine the best treatment options for depression, according to a Stanford-led trial.

Stanford researchers and their collaborators used electroencephalography, a tool for monitoring electrical activity in the brain, and an algorithm to identify a brain-wave signature in individuals with depression who will most likely respond to sertraline, an antidepressant marketed as Zoloft.

A paper describing the work will be published Feb. 10 in Nature Biotechnology.

The study emerged from a decades-long effort funded by the National Institute of Mental Health to create biologically based approaches, such as blood tests and brain imaging, to help personalize the treatment of depression and other mental disorders. Currently, there are no such tests to objectively diagnose depression or guide its treatment.

"This study takes previous research showing that we can predict who benefits from an antidepressant and actually brings it to the point of practical utility," said Amit Etkin, MD, PhD, professor of psychiatry and behavioral sciences at Stanford. "I will be surprised if this isn't used by clinicians within the next five years."

Instead of functional magnetic resonance imaging, an expensive technology often used in studies to image brain activity, the scientists turned to electroencephalography, or EEG, a much less costly technology.

Etkin shares senior authorship of the paper with Madhukar Trivedi, MD, professor of psychiatry at the University of Texas-Southwestern. Wei Wu, PhD, an instructor of psychiatry at Stanford, is the lead author.

The paper is one of several based on data from a federally funded depression study launched in 2011 -- the largest randomized, placebo-controlled clinical trial on antidepressants ever conducted with brain imaging -- which tested the use of sertraline in 309 medication-free patients. The multicenter trial was called Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care, or EMBARC. Led by Trivedi, it was designed to advance the goal of improving the trial-and-error method of treating depression that is still in use today.

"It often takes many steps for a patient with depression to get better," Trivedi said. "We went into this thinking, 'Wouldn't it be better to identify at the beginning of treatment which treatments would be best for which patients?'"

Most common mental disorder

Major depression is the most common mental disorder in the United States, affecting about 7% of adults in 2017, according to the National Institute of Mental Health. Among those, about half never get diagnosed. For those who do, finding the right treatment can take years, Trivedi said. He pointed to one of his past studies that showed only about 30% of depressed patients saw any remission of symptoms after their first treatment with an antidepressant.

Current methods for diagnosing depression are simply too subjective and imprecise to guide clinicians in quickly identifying the right treatment, Etkin said. In addition to a variety of antidepressants, there are several other types of treatments for depression, including psychotherapy and brain stimulation, but figuring out which treatment will work for which patients is based on educated guessing.

To diagnose depression, clinicians rely on a patient reporting at least 5 of 9 common symptoms of the disease. The list includes symptoms such as feelings of sadness or hopelessness, self-doubt, sleep disturbances -- ranging from insomnia to sleeping too much -- low energy, unexplained body aches, fatigue, and changes in appetite, ranging from overeating to undereating. Patients often vary in both the severity and types of symptoms they experience, Etkin said.

"As a psychiatrist, I know these patients differ a lot," Etkin said. "But we put them all under the same umbrella, and we treat them all the same way." Treating people with depression often begins with prescribing them an antidepressant. If one doesn't work, a second antidepressant is prescribed. Each of these "trials" often takes at least eight weeks to assess whether the drug worked and symptoms are alleviated. If an antidepressant doesn't work, other treatments, such as psychotherapy or occasionally transcranial magnetic stimulation, may also be tried. Often, multiple treatments are combined, Etkin said, but figuring out which combination works can take a while.

"People often feel a lot of dejection each time a treatment doesn't work, creating more self-doubt for those whose primary symptom is most often self-doubt," Trivedi said.

Looking for a biomarker

The EMBARC trial enrolled 309 people with depression who were randomized to receive either sertraline or a placebo.

For their study, Etkin and his colleagues set out to find a brain-wave pattern to help predict which depressed participants would respond to sertraline. First, the researchers collected EEG data on the participants before they received any drug treatment. The goal was to obtain a baseline measure of brain-wave patterns.

Next, using insights from neuroscience and bioengineering, the investigators analyzed the EEG using a novel artificial intelligence technique they developed and identified signatures in the data that predicted which participants would respond to treatment based on their individual EEG scans. The researchers found that this technique reliably predicted which of the patients did, in fact, respond to sertraline and which responded to placebo. The results were replicated at four different clinical sites.

Further research suggested that participants who were predicted to show little improvement with sertraline were more likely to respond to treatment involving transcranial magnetic stimulation, or TMS, in combination with psychotherapy.

"Using this method, we can characterize something about an individual person's brain," Etkin said. "It's a method that can work across different types of EEG equipment, and thus more apt to reach the clinic."

Etkin is on leave from Stanford, working as the founder and CEO of the startup Alto Neuroscience, a company based in Los Altos, California, that aims to build on these findings and develop a new generation of biologically based diagnostic tests to personalize mental health treatments with a high degree of clinical utility. "Part of getting these study results used in clinical care is, I think, that society has to demand it," Trivedi said. "That is the way things get put into practice. I don't see a downside to putting this into clinical use soon."

Broad effort

When EMBARC was launched, it was part of a broader effort by the NIMH to push for improvements in mental health care by using advances in fields such as genetics, neuroscience and biotechnology, said Thomas Insel, MD, who served as director of that institute from 2002 to 2015.

"We went into EMBARC saying anything is possible," Insel said. "Let's see if we can come up with clinically actionable techniques." He didn't think it would take this long, but he remains optimistic.

"I think this study is a particularly interesting application of EMBARC," he said. "It leverages the power of modern data science to predict at the individual level who is likely to respond to an antidepressant."

In addition to improving care, the researchers said they see a possible side benefit to the use of biologically based approaches: It could reduce the stigma associated with depression and other mental health disorders that prevents many people from seeking appropriate medical care.

"I'd love to think scientific evidence will help to counteract this stigma, but it hasn't so far," said Insel. "It's been over 160 years since Abraham Lincoln said that melancholy 'is a misfortune, not a fault.' We still have a long way to go before most people will understand that depression is not someone's fault." (President Lincoln suffered bouts of depression.)

Working in close partnership with patients, scientists at the Broad Institute of MIT and Harvard, Dana-Farber Cancer Institute, and Count Me In have identified new causes of a rare cancer of blood vessel walls called angiosarcoma. The research also points to possible therapeutic options for patients with this aggressive disease, who often have a poor prognosis.

The study is a result of the Angiosarcoma Project, a unique partnership between patients and scientists that empowers patients to contribute their medical records, biological samples, and voices to accelerate research. The work also shows how a crowd-sourced effort that unites a small and scattered group of patients can yield unexpected findings about a disease that has been difficult to study because it is so rare.

In the study, published in Nature Medicine, the researchers analyzed the genomes of nearly 50 tumor samples donated by angiosarcoma patients from across the United States and Canada. The team found dozens of mutated genes in various forms of the cancer, as well as clues suggesting that drugs approved for other types of cancer might be useful in treating some kinds of angiosarcoma.

"This work was only possible with our patient partners," said senior author Nikhil Wagle, an institute member at the Broad, a medical oncologist at Dana-Farber, an assistant professor at Harvard Medical School, and director of Count Me In. "The scientific insights they've helped generate have shed new light on the poorly understood roots of angiosarcoma, which urgently needs new treatment options for patients."

"When we saw the data for the first time, we were excited to see these discoveries were evident from the genomic data from the very beginning," said co-first author Corrie Painter, associate director of operations and scientific outreach for the Broad Cancer Program and associate director of Count Me In. "Working with patients to design and build the project from the start has been a phenomenal experience." Painter, a scientist, became a patient advocate after her own angiosarcoma diagnosis in 2010.

Patient partnership

The Angiosarcoma Project launched in 2017 and is part of Count Me In, which aims to catalyze research on several cancer types by directly engaging cancer patients online to enroll in biomedical studies, no matter where they live in the United States or Canada. Count Me In was built off the success of the initial effort, the Metastatic Breast Cancer (MBC) Project, which has also resulted in numerous discoveries. The Angiosarcoma Project aimed to assess this model of patient partnership in the context of a rare disease, where research is greatly needed to improve patient outcomes.

Angiosarcoma arises in endothelial cells, which form the inner linings of blood vessels and can occur anywhere in the body, but it is most commonly found in the skin, breast, liver, and spleen. It is an extremely rare cancer, with only 300 new cases each year in the United States, and prognosis is generally poor. Patients are scattered across the country, so large studies to find the illness's molecular underpinnings have not been feasible until now.

The ASCproject team established a social media working group to connect patients with angiosarcoma and loved ones online and invite them to help shape the project's outreach strategy. With feedback from patient partners, the team built an online portal at ascproject.org that allows patients in the U.S. and Canada to join the study and contribute their medical history and tumor or blood samples for DNA testing. Within 18 months of launching the ASCproject, 338 patients had registered, a large proportion of all patients in the U.S. with angiosarcoma.

With patient consent, the project staff obtained medical records and tumor samples from a subset of the registered patients. The Broad's Genomics Platform sequenced the exome, or protein-coding regions, of 47 of these tumor samples along with germline (inherited) DNA from the same patients. Co-first author Esha Jain, a computational biologist in the Wagle lab, led the analysis of the data, which revealed 30 genes that were frequently mutated in several tumors. Some of these genes had never been associated with angiosarcoma, such as PIK3CA, GRIN2A, and NOTCH2.

Potential treatment options

Most of the samples with mutations in PIK3CA were in cases of angiosarcoma of the breast. The researchers looked at where the mutations fell in the gene itself and deduced that they were likely to be "activating" mutations, meaning they give the protein a new or enhanced function. This suggests that blocking the PIK3CA pathway with an FDA-approved drug known as a PI3 kinase inhibitor could be helpful for patients with breast angiosarcomas that carry one of these mutations.

The PIK3CA gene is also mutated in breast adenocarcinoma, a different type of cancer that happens to occur in the same tissue, suggesting that something about the cellular environment of the breast encourages these tumors to develop.

"Findings like this can really open up the doors in terms of how we think about genes in tissue-specific contexts for cancer tumorigenesis," said Painter. "We never would have had that insight without this data."

The team measured the tumors' overall rate of mutation and learned that angiosarcomas of the head, neck, face, and scalp (HNFS) have a higher burden of mutations than the others. The pattern of those mutations has previously been linked to damage from ultraviolet radiation, suggesting that sun damage may have led to disease in these patients.

Because other tumors with excessive mutations have responded to treatment with drugs known as immune checkpoint inhibitors (ICIs), the researchers hypothesized that these medicines might help patients with HNFS. In fact, they found two patients in the study with HNFS angiosarcoma who, after failing to respond to standard treatments, were given off-label ICIs and responded exceptionally well to the therapy. Despite needing to discontinue the treatment because of side effects, those patients remain disease-free today without any further treatment for their cancer. This suggests that ICIs could potentially help some patients with this subtype.

Growing impact

More work is needed to prove whether these non-standard treatments are effective for patients, but the findings have invigorated angiosarcoma research. At least three clinical trials are underway that now include angiosarcoma patients because of the data in this study, which was shared with the scientific and medical community before publication.

The ASCproject continues to enroll patients and analyze data, and it has now reached nearly 500 registered patients. "It was an aspirational goal that I honestly didn't know if we would ever reach, let alone achieve in two and a half years," said Painter.

Jim Chapdelaine, a guitarist and Emmy Award-winning recording musician in Hartford, Connecticut, was first diagnosed with angiosarcoma in 1976. He enrolled in the study in the hopes that his experience as an exceptionally long-lived survivor might help benefit other patients. "It feels amazing to know that I and others in the patient community helped fuel these new discoveries," he said. "I hope for a cure one day, but this study helps open scientific doors and we hope that people will now walk through them."

Painter explained that the new findings are hopeful, but also bittersweet, as she remembers friends in the angiosarcoma community who did not survive the illness. "The participants in the ASCproject have signed up in the hopes that this will help people down the road," she said. "We are grateful that in the midst of their own diagnosis, they wanted to do their part to help prevent the suffering of other patients."

A new Boston University School of Public Health (BUSPH) study finds that the proportion of high school students identifying as lesbian, gay, bisexual, or questioning (LGBQ) doubled from 2009 to 2017, while the LGBQ teen rate of attempted suicide went from five times the rate for their straight peers to nearly four times the rate. The study was published in the journal Pediatrics.

"Large disparities in suicide attempts persisted even as the percent of students identifying as LGBQ increased. In 2017, more than 20% of LGBQ teens reported attempting suicide in the past year," says study lead author Dr. Julia Raifman, assistant professor of health law, policy & management at BUSPH.

"It's critical that health and educational institutions have policies and programs in place to protect and improve LGBQ health, such as medical school curricula and high school health curricula that are inclusive of sexual minority health," she says.

Raifman says LGBQ rights also play a particularly important role in shaping mental health. In a 2017 study, Raifman found that states' legalization of same-sex marriage came with a 7% decrease in all high school student suicide attempts. She notes that other research (including a 2018 study she led) has shown that anti-LGBQ policies harm the mental health of LGBQ adults and teens. "Our new paper indicates that an increasing number of teenagers are identifying as LGBQ, and will be affected by anti-LGBQ policies that may elevate these already very high rates of suicide attempts" she says.

For the new paper, the researchers used Youth Risk Behavioral Surveillance Survey (YRBSS) data from the only six states that collected sexual orientation data continuously between 2009 and 2017: Delaware, Illinois, Massachusetts, Maine, North Dakota, and Rhode Island. Of these states, only Connecticut, Delaware, Illinois, and Rhode Island collected data on the sex of sexually-active students' partners, and distinguished between consensual sexual contact and sexual assault. This left the researchers with sexual orientation data for 110,243 high school students, and data on the consensual sexual behavior of 25,994 of these students. (None of the states consistently collected data on transgender students.)

The researchers found that the proportion of high schoolers identifying as LGBQ doubled from 7.3% in 2009 to 14.3% in 2017, with similar trends for identifying as gay/lesbian (1.4% to 2.8%), bisexual (3.9% to 7.2%), and unsure/questioning (2.0% to 4.3%). The proportion of sexually active high schoolers who reported consensual, same-sex sexual contact increased from 7.7% to 13.1%.

In both 2009 and 2017, about 6% of heterosexual high schoolers reported attempting suicide in the previous 12 months, while the rate for LGBQ teens decreased from 26.7% in 2009 to 20.1% in 2017. Adjusting for other student characteristics, the researchers found the LGBQ suicide attempt rate went from 5.2 to 3.8 times the heterosexual rate. They did not find significant changes in the rate of suicide attempts among high schoolers who had had same-sex or only heterosexual sexual contact, although the rate remained about twice as high for those reporting any same-sex sexual contact.

As the coronavirus outbreak expands, public health officials are trying to anticipate its trajectory and the rate at which it will travel. Now, scientists have created a new analysis able to predict the speed of epidemics in a network. By employing a simple approach commonly used to monitor how messages pass through communication networks, Moore and Rogers were able to theoretically predict contagion speeds in different networks, down to individual nodes. Their model also provides a way to assess each node's likelihood of being infected by a certain particular time in the epidemic. Currently, the theoretical analysis operates in a tree-like contagion network. However, the scientists demonstrate how it can be applied to more complex and widespread contagion networks.

Predicting the speed of epidemics spreading on networks
Sam Moore and Tim Rogers

In the decade-long absence of federal action, many states, counties and cities have increased minimum wages to help improve the lives of workers. While political debate over these efforts has long been contentious, scientific research on the health effects of raising the minimum wage is relatively new.

Some studies have found higher minimum wages associated with positive health outcomes, with little evidence that minimum wages harm health. However, a new study by researchers at the University of Washington found that increases in minimum wages primarily had no effect on health overall. However, they did find a mix of negative and positive effects associated with the health of certain groups of working-age people.

The UW study, published Feb. 10 in the American Journal of Epidemiology, looked at more than 131,000 adults who provided information to the federal National Health Interview Survey between 2008 and 2015. The subjects were 25 to 64 years old and were either employed or unemployed but looking for work.

"We found that an increase in minimum wage really didn't have a huge impact on health overall, which surprised us," said lead author James Buszkiewicz, a doctoral student in epidemiology in the UW School of Public Health. "We did see, when we looked at subgroups, some mixed health effects there, however."

For example, the researchers found that a wage increase was associated with an increased likelihood of obesity and elevated body mass index in working-age people of color. They also found that higher minimum wages were associated with a lower likelihood of hypertension among working-age men but higher likelihood of hypertension in working-age women.

"These mixed results shine a spotlight on segments of the population that need to be studied in relation to rising minimum wages in order to learn how best to achieve the goal of reducing inequality with adjustments to the minimum wage," said co-author Heather Hill, an associate professor in the UW Evans School of Public Policy & Governance.

The researchers looked at several health outcomes: obesity, body mass index, hypertension, diabetes, fair or poor general health and serious psychological distress. And, to make sure they were seeing results tied to minimum wages and not other factors, they compared the health outcomes of working-age people with less formal education -- who are most likely to receive the minimum wage ¬¬-- to health outcomes of those with more formal education. If a health outcome appeared in both groups, the researchers could assume that it wasn't caused by changes to the minimum wage.

According to the researchers, these types of analyses and comparisons set their study apart from previous research on this topic. This gives the team confidence in its main finding -- no overall effect on the health of working-age people -- even though that result contradicts previously published studies. In addition, the UW study provides detailed data on the effects of minimum wage increases on subgroups of workers based on gender, race and age.

The team points out in the study that an association between higher minimum wage and higher rates of obesity for a specific subgroup of working-age people may reflect differences in how minimum-wage policies affect certain demographics of workers, especially those more likely to have low- or minimum-wage jobs.

The researchers did not explore in this study the obesity or hypertension differences they uncovered, but believe that these results point to potential consequences of minimum-wage policy that should be the focus of future research.

"When we are looking at a minimum-wage policy, or any policy for that matter, we should be looking at the effect overall, but we should also consider how it is affecting different groups. And, if there is evidence that minimum wage or any policy is affecting groups differently, that's something to hone in on for further investigation," said Buszkiewicz, who is expanding his research into the minimum wage to include its effects over time and by gender and race.

The authors also point out that this research could help inform policymakers when it comes to establishing wage policy.

"Cities and counties are increasing minimum wages with very good intentions, which is to benefit lower-earning workers and reduce inequality, and yet we still need more research evidence on the effects of the minimum wage on health." Hill said. "In particular, we need to understand how it affects different types of workers differently."

New research indicates that a single dose of the human papillomavirus (HPV) vaccine is as effective as multiple doses for preventing preinvasive cervical disease, which can later develop into cervical cancer. The findings are published early online in CANCER, a peer-reviewed journal of the American Cancer Society (ACS).

HPV is the most common sexually transmitted infection in the United States, and persistent infection with certain types of the virus can cause cervical cancer. To prevent infection, the Centers for Disease Control and Prevention recommends that adolescents--both boys and girls--under the age of 15 years receive a two-dose schedule of the HPV vaccine. To determine the effectiveness of other dose schedules, Ana M. Rodriguez, MD, MPH, of The University of Texas Medical Branch at Galveston, and her colleagues examined information on females aged 9 to 26 years who were unvaccinated or who received one or more HPV vaccine doses between January 2006 and June 2015.

The analysis included 133,082 females (66,541 vaccinated and 66,541 unvaccinated). For females ages 15 to 19 years, those who received one, two, or three doses of the HPV vaccine had lower rates of preinvasive cervical disease than adolescents who were unvaccinated. Within five years, 2.65 percent of unvaccinated teens aged 15 to 19 years developed preinvasive cervical disease, compared with 1.62 percent, 1.99 percent, and 1.86 percent in the one-, two- and three-dose groups, respectively. The risk of preinvasive cervical disease was 36 percent, 28 percent, and 34 percent lower for adolescents who received one, two, and three doses, respectively, compared with adolescents who were unvaccinated.

For the youngest (less than 15 years old) and oldest age groups (20 years and older), the investigators did not find significant differences among the vaccinated groups in terms of risk for preinvasive cervical disease.

"This study shows the impact of vaccinating at younger ages and its lasting long-term protection against cervical cancer," said Dr. Rodriguez. "It is important to educate parents about the need to vaccinate their children."

An accompanying editorial discusses the public health implications of the study's findings. "If one dose of HPV vaccine was sufficient for effective protection, HPV vaccine implementation and scale-up would require less logistics..., available doses could extend further, and the overall cost would be lower," the authors wrote.

February is National Cancer Prevention Month.

A new article in CMAJ (Canadian Medical Association Journal) reviews evidence that suggests an association between excessive smartphone and social media use and mental distress and suicidality among adolescents. The authors say this should be among the factors considered by clinicians and researchers who work in the field of youth mental health: http://www.cmaj.ca/lookup/doi/10.1503/cmaj.190434

The analysis, led by The Hospital for Sick Children (SickKids), focuses on smartphone use and does not consider online gaming. It contains guidance for physicians, parents and teachers on how to help teens manage smartphone and social media use for a healthy balance between sleep, academic work, social activity, interpersonal relationships and online activity.

"Physicians, teachers and families need to work together with youth to decrease possible harmful effects of smartphones and social media on their relationships, sense of self, sleep, academic performance, and emotional well-being," says lead author Dr. Elia Abi-Jaoude, Staff Psychiatrist, SickKids, and Toronto Western Hospital, University Health Network, Toronto, Ontario.

Topics discussed in the analysis include:

What are the effects of social media on adolescents' sense of self?

Can social media encourage self-harm?

Does excessive smartphone use affect mental health?

How does social media and smartphone use affect sleep required for mental health?

Are some teens more vulnerable to mental health effects than others?

How can physicians use this information in clinical practice?

"Given the importance of engaging youth in mitigating potential harms from social media, a prohibitionist approach would be counterproductive," write the authors.

"For adolescents today, who have not known a world without social media, digital interactions are the norm, and the potential benefits of online access to productive mental health information -- including media literacy, creativity, self-expression, sense of belonging and civic engagement -- as well as low barriers to resources such as crisis lines and Internet-based talking therapies cannot be discounted."

Suggestions to help teens manage smartphone and social media use include:

Physicians - Recommend teens reduce social media use rather than eradicate it completely. Encourage parents to be part of the conversations.

Parents - Discuss appropriate smartphone use with teenagers to determine together how to reduce risks and set boundaries. Model responsible smartphone use.

Schools - Negotiate developmentally appropriate smartphone use in the context of a relationship built on mutual trust and respect for autonomy.

Resources, such as the American Academy of Pediatrics Family Media Use Plan, a Family Media Toolkit and information from the Center for Humane Technology provide tips on how to develop social media use plans and support youth.

A recent poll from the US indicates that 54% of teens think they spend too much time on their smartphones and about half said they were cutting back on usage.

"Encouragingly, youth are increasingly recognizing the negative impact of social media on their lives and starting to take steps to mitigate it," write the authors.

Higher maternal blood pressure in pregnancy is associated with chemical modifications to placental genes, according to a study by researchers from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), part of the National Institutes of Health (NIH). The changes involve DNA methylation, the binding of compounds known as methyl groups to DNA, which can alter a gene's activity. Exposure to high blood pressure in the womb increases the risk for impaired fetal growth and the risk for cardiovascular disease in adult life. Ultimately, the findings could yield information on the earliest origins of cardiovascular disease and how to prevent it from occurring.

The researchers conducted a comprehensive genetic analysis, called an epigenome-wide association study (EWAS), on biopsies of placentas delivered from 301 pregnant women in the NICHD Fetal Growth Study. EWAS detects DNA methylation and other changes to gene functioning. The authors believe their study is the first EWAS to compare placental DNA methylation to maternal blood pressure across trimesters. The study team found distinct patterns of DNA methylation in the placental tissue, which corresponded with the timing of blood pressure elevations in pregnancy. Many of the methylated genes were found in earlier studies to be involved in cardiovascular functioning.

The researchers hope to study patterns of DNA methylation in larger groups of pregnant women, including those with pregnancy-associated blood pressure disorders such as preeclampsia.