Body

GALVESTON, Texas -More than 2.5 million people in the United States alone experience a traumatic brain injury, or TBI, each year. Some of these people are plagued by a seemingly unrelated cascade of health issues for years after their head injury, including fatigue, depression, anxiety, memory issues, and sleep disturbances.

A collaborative team, led by Dr. Randall Urban, The University of Texas Medical Branch at Galveston's Chief Research Officer and Professor of Endocrinology, has spent the past 20 years investigating this post-TBI syndrome. The team has learned more about how a TBI triggers a reduction in growth hormone secretion and why most TBI patients improve after growth hormone replacement treatment.

The studies led to the definition of the syndrome as brain injury associated fatigue and altered cognition, or BIAFAC, as recently described in a commentary published by Drs Urban and Brent Masel, UTMB Professor of Neurology, in the Journal of Neurotrauma. Detailed information on the team's two most recent advances also in the Journal of Neurotrauma.

The team's work on brain injuries began in the late 1990's when Galveston philanthropist Robert Moody asked the team whether TBI caused dysfunction of the hormones made by the brain's pituitary gland and funded research for the study. His son, Russell, had suffered a serious TBI during a car accident and was seeking ways to improve the life of his son and others living with brain injuries.

The team has been building on the discovery that TBI triggers a long-term reduction in growth hormone, or GH, secretion that is linked with BIAFAC. Most TBI patients experience dramatic symptom relief with GH replacement therapy, but the symptoms return if the treatment stops. The researchers are trying to better understand BIAFAC and exactly how and why GH replacement works so well in order to develop new interventions.

"We already knew that even mild TBI triggers both short- and long-term changes to functional connections in the brain," said Urban. "GH administration has been extensively linked with both protection and repair of the brain following damage or disease, however we didn't know much about the particular mechanisms and pathways involved."

They examined 18 people with a history of mild TBI and inadequate GH secretion. The subjects received GH replacement in a year-long, double-blind, placebo-controlled study and were assessed for changes in physical performance, resting metabolic rate, fatigue, sleep quality, and mood. Functional magnetic resonance imaging was also used throughout the year to assess changes in brain structure and functional connections.

The study showed that GH replacement was linked with increased lean body mass and decreased fat mass as well as reduced fatigue, anxiety, depression and sleep disturbance. It was also found, for the first time, that these improvements were associated with better communications among brain networks that have been previously associated with GH deficiency. They also noted increases in both grey and white matter in frontal brain regions, the "core communications center of the brain," that could be related to cognitive improvements.

"We noticed that TBI patients had altered amino acid and hormonal profiles suggesting chronic intestinal inflammation, so we recently completed a trial to investigate the role of the gut-brain axis in the long-lasting effects of TBI," said Urban. "We compared the fecal microbes of 22 moderate/severe TBI patients residing in a long-term care facility with 18 healthy age-matched control subjects, identifying disruptions of intestinal metabolism and changes in nutrient utilization in TBI patients that could explain the reduced growth hormone function."

The results suggest that the people with TBI-related fatigue and altered cognition also have different fecal bacterial communities than the control group. Urban said that the findings suggest that supplementing or replacing the dysbiotic intestinal communities may help to ease the symptoms experienced after TBI.

"These two studies further characterize BIAFAC and act as a springboard for new treatment options," said Urban. "We hope that the publications will focus the collective wisdom of the research community to better understand and treat this syndrome, providing hope for many. Because these symptoms can manifest months to years after the initial injury and as this cluster of symptoms hasn't been previously grouped together, it often goes unidentified in the medical community."

An analysis of national data on buprenorphine use found that treatment with the FDA-approved medication for opioid addiction is increasing in all age groups except the young (age 15-24 years), in whom use of the medication is decreasing.

The findings were published in JAMA.

"While it's encouraging to see an overall increase in prescription rates for buprenorphine, the data suggest that the youngest group is having difficulty accessing this potentially lifesaving treatment," says the study's leader Mark Olfson, MD, MPH, the Elizabeth K. Dollard Professor of Psychiatry, Medicine, and Law at Columbia University Vagelos College of Physicians and Surgeons.

The study is the first to evaluate national trends in buprenorphine treatment.

Over the study period, annual rates of buprenorphine use more than doubled--from 1.97 per 1,000 people in 2009 to 4.43 per 1,000 people in 2018.

While increases in buprenorphine use varied among different age groups, medication use decreased by around 20% in the youngest group, from 1.76 to 1.40 per 1,000 people. Compared with older peers, treatment duration and prescription strength were also lower for this age group.

"These findings for young people are particularly worrisome, given that their decrease in buprenorphine treatment occurred during a period when there was an increase in opioid-related overdose deaths for this age group," says Olfson.

The researchers note that although overall rates of buprenorphine use are on the rise, they are still lower than national estimates of those with opioid use disorder (including prescription opioids and heroin).

"Our results highlight the critical need to improve buprenorphine treatment services, especially for the youngest with opioid use disorder," says Olfson.

Bottom Line: A randomized clinical trial with 48 healthy volunteers assessed the absorption of six active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate and octinoxate) in four sunscreen products formulated as lotion and sprays (aerosol, nonaerosol and pump). This study builds on a prior trial from Food and Drug Administration (FDA) researchers published by JAMA in 2019. In this trial, all six tested active ingredients administered in four different sunscreen formulations were absorbed and had blood concentrations that surpassed the FDA threshold for potentially waiving some of the additional safety studies for sunscreens. Researchers emphasize the findings don't mean people should refrain from using sunscreen, which can help to prevent skin cancer and protect the skin. More research is needed to determine the effect of exposure to sunscreen ingredients. This study was conducted indoors in a clinical research setting and participants weren't exposed to direct sunlight during the seven days they remained at the clinic. A change in study design from an indoor to an outdoor setting would better represent real-life sunscreen application. The study also wasn't designed to assess the absorption difference by formulation or skin types.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: David G. Strauss, M.D., Ph.D., U.S. Food and Drug Administration, Silver Spring, Maryland, and coauthors.

(doi:10.1001/jama.2019.20747)

Editor's Note: The study was funded by the FDA. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Rutgers researchers have found that a Texas strategy to reduce anti-psychotic medication for children can serve as a model for other state Medicaid programs.

The study was published in the Journal of the American Academy of Child & Adolescent Psychiatry.

"Youth in the United States foster care system are about five times more likely to take antipsychotic medications, a class of medications to manage their mental and behavioral health, than children in the general public," said Thomas Mackie, assistant professor at Rutgers School of Public Health. In response, over 31 state Medicaid programs nationally are experimenting with different approaches to ensure safe and judicious use of antipsychotic medications. These Medicaid programs are challenged to address these concerns while also ensuring access to antipsychotic medications is maintained for youth whom they are clinically optimal, especially those with psychosis, autism and other U.S. Food and Drug Administration-approved clinical indications.

The Texas strategy includes four elements: a mental health screening administered within 72 hours of the child being removed from the original caregiver; a health passport drawing on claims-based data; a psychiatric consultation line for child welfare staff, caregivers and judges; and a retrospective review of whether prescribed psychotropic medications met state best practice parameters after the antipsychotic medication was prescribed and dispensed.

The study sought to examine whether this program was effective in reducing the number of youth in foster care prescribed antipsychotic medications off-label to manage symptoms of conditions such as conduct disorders or attention hyperactivity disorders, while not decreasing use for disorders with FDA indications, such as bipolar disorder or autism spectrum disorders.

After the strategy started, the Rutgers researchers found the program resulted in roughly a 5 percent to 8 percent reduction in antipsychotic use for youth treated off-label for conditions like conduct or attention hyperactivity disorders, whereas no significant changes were found for youth treated for FDA-indicated conditions.

These findings show that the Texas program effectively reduced use of antipsychotic medications for off-label conditions where clinical concerns are greatest while not reducing antipsychotic medications for FDA-indicated conditions where stronger evidence exists for antipsychotic use among youth.

"Although the Texas model enrolled only youths in foster care, similar innovations are increasingly being extended to the general population of Medicaid-insured youth," Mackie said. "This study provides important new evidence suggesting that states continue to incorporate or renew the inclusion of these additional behavioral health services into Medicaid-managed care arrangements."

Researchers have identified 107 genes that increase a person's risk of developing the eye disease glaucoma, and now developed a genetic test to detect those at risk of going blind from it.

The research, led by QIMR Berghofer Medical Research Institute and Flinders University in Australia, has been published today in the international Nature Genetics journal.

In a world first, genetic information from tens of thousands of people around the world has been used to develop a test to identify individuals at risk of developing glaucoma, the leading cause of irreversible blindness globally.

The new test means glaucoma, which affects about 76 million people worldwide, can be more accurately predicted using a single blood or saliva sample.

Once accredited for use, the test will improve doctors' ability to predict and prevent vision loss from glaucoma. It will also guide the age at which screening for glaucoma should start, and the level of risk to other family members.

The researchers now want 20,000 people to sign up to their Genetics of Glaucoma study so they can find more genes involved in the disease.

Glaucoma is a group of diseases that are characterised by progressive damage and degeneration of the optic nerve, causing gradual loss of vision.

It is the leading cause of irreversible blindness worldwide and is predicted to affect 76 million people by 2020.

Although there is no cure for glaucoma, treatment can reliably slow or halt the rate of disease progression in most cases. Up to 50 per cent of people with the disease do not know they have it.

Lead researcher and head of QIMR Berghofer's Statistical Genetics Group, Associate Professor Stuart MacGregor, says identifying the new genes has allowed the researchers to develop a glaucoma polygenic risk score (PRS) that can predict who is likely to get the eye disease.

"Glaucoma is a genetic disease and the best way to prevent the loss of sight from glaucoma is through early detection and treatment," says Associate Professor MacGregor.

"Our study found that by analysing DNA collected from saliva or blood, we could determine how likely a person was to develop the disease and who should be offered early treatment and or monitoring.

"Importantly, unlike existing eye health checks based on eye pressure or optic nerve damage, the genetic test can be done before damage begins so regular screening can be put in place.

"Having a high risk score doesn't mean you will definitely get glaucoma, but knowing you could be at future risk allows people to take the necessary precautions."

Clinical lead researcher and Chair and Academic Head of Ophthalmology at Flinders University, Professor Jamie Craig, says the study results provides hope that mass screening for glaucoma could be offered in the future.

"There are Australians who, if they'd had appropriate treatment a few years earlier, wouldn't have gone blind," says Professor Craig, who is also a consultant ophthalmologist.

"One in 30 Australians has glaucoma, but most people only find out they have it when they go to the optometrist because they are losing vision, or for a general eye check".

"Early detection is paramount because existing treatments can't restore vision that has been lost, and late detection of glaucoma is a major risk factor for blindness.

"Glaucoma can arise at any age but most of those affected are in their 50s or older, so our ultimate aim is to be able to offer blood tests to people when they turn 50 so they can find out if they are at risk, and then hopefully act on it.

"In most cases, glaucoma can be treated easily using simple eye drops, but this test is likely to be helpful in identifying those who would benefit from more aggressive intervention such as surgery."

The researchers are now hoping to recruit 20,000 people with a personal or family history of the disease to join their Genetics of Glaucoma study so that they can identify more genes that play a role in the condition.

"We want to know who will get glaucoma, and for those who are susceptible, we want to be able to pinpoint at what age they're going to get it," Associate Professor MacGregor says.

"That would allow us to develop a personalised approach for earlier treatment of high-risk individuals, and mean people at lower risk could have less intensive monitoring and treatment. This would have benefits for patients, doctors and the health care system with reduced interventions and reduced costs."

Inflammatory bowel disease (IBD) is a category of refractory inflammatory disease, of which ulcerative colitis (UC) and Crohn's disease (CD) are the main types.

Current studies suggest that IBD is a complex autoinflammatory disease determined by genetic and environmental factors, and is the major cause of gastrointestinal cancer. Because of its complex and refractory character, researchers have focused on determining the detailed pathogenesis of IBD and finding an effective therapy for it.

In a study published online in PNAS on Jan. 20, Prof. SUN Bing's team from the Center for Excellence in Molecular and Cellular Science, Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences, in collaboration with Prof. LIU Jie from Huashan Hospital, Fudan University, revealed a new mechanism involved in the pathogenesis of IBD and suggested therapeutic targets for clinical trial.

Among the identified IBD-susceptibility genes (NOD2, IL-23, etc.), extracellular matrix protein-1 (ECM1) gene was found to be strongly related to UC in 2008. Since 2011, several studies from SUN's lab have reported the disease-related functions of ECM1 in Th2, Th17 and Tfh cells. However, no available evidence suggested that ECM1 plays a direct role in IBD.

In this study, the researchers analyzed tissue samples from patients with ulcerative colitis and a DSS-induced IBD mice model.

They found that ECM1 was highly expressed in macrophages, particularly tissue-infiltrated macrophages under inflammatory conditions, and ECM1 expression was significantly induced during IBD progression. The macrophage-specific knockout of ECM1 resulted in increased arginase 1 (ARG1) expression and impaired polarization into the M1 macrophage phenotype after lipopolysaccharide (LPS) treatment.

Further study showed that ECM1 protein could regulate M1 macrophage polarization through the GM-CSF/STAT5 signaling pathway. Pathological changes in mice with dextran sodium sulfate-induced IBD were alleviated by the specific knockout of the ECM1 gene in macrophages.

These results reveal a role for the IBD-susceptibility gene ECM1 in colitis and the possible existence of a GM-CSF/STAT5 regulatory axis in macrophages, indicating that the attenuation of ECM1 function in macrophages is a potential strategy for IBD therapy.

WINSTON-SALEM, NC - JAN. 20, 2020 - A patient-specific tumor organoid platform developed by Wake Forest Institute for Regenerative Medicine (WFIRM) researchers and their cancer center colleagues could someday take the guessing game out of immunotherapy treatments. The hope is that, one day, these tumor organoids will be used to personalize patients' treatments, to focus on those that will best help them fight their own cancer.

"Immunotherapy drugs are not inexpensive, and it is not uncommon for the cost of therapy to be measured in millions of dollars per patient," said senior author Aleks Skardal, PhD, who was an assistant professor at WFIRM at the time of the study. "This bioengineered patient-specific tumor model opens the door to speedier drug screening to get the best therapy to patients as soon as possible and rationalize the use of immunotherapy drugs to the patients that will show a clinical response."

The work is detailed in a paper published recently in the journal Annals of Surgical Oncology.

For this study, the researchers were able to combine melanoma cells and white blood cells from the patients' peripheral blood and lymph nodes, and create patient-specific, immune-active tumor organoids to test their response to immunotherapy treatment. For many cancers, immune response is only possible after appropriate exposure of the specific immune cells, T-cells, to tumor antigens. However, tumor cells develop mechanisms to evade the immune system and go unnoticed. Immunotherapy allows these T-cells to re-detect tumor cells and eventually kill them.

"These constructs will potentially allow us to predict immunotherapy effectiveness and generate adaptive immunity at the level of the individual patient," said leading author Konstantinos Votanopoulos, MD, PhD, associate professor of surgical oncology at the Wake Forest Comprehensive Cancer Center (WFCCC) and co-director of the Wake Forest Organoid Research Center (WFORCE). "Our team has previously co-cultured lymph nodes and tumor from the same patient for screening purposes, but this is the first time we have used this platform to train the immune system of the patient to directly recognize and kill their own tumor without the use of drugs. Creating such a clinically relevant model has the potential to revolutionize the way we approach both cancer research and cancer care."

Organoids are tiny, 3D tissue-like structures created in the laboratory that mimic the function of human tissues and organs such as the heart, liver, lung, blood vessels, as well as cancer. The organoids are used as a testing and predicting platform to model diseases, evaluate efficacy and/or toxicity of new and existing drugs, and can also be used to test environmental hazards.

To construct the platforms, tumor cells and lymph node biospecimens were surgically obtained from eight patients with stage III and IV melanoma and co-cultured to create the organoids. From the biospecimens received, an average of 75 to 100 organoids were created in each instance and were typically split into equal numbers of patient tumor organoids and immune-enhanced patient tumor organoids. Immunotherapy testing was initiated on day 7 and the organoids were incubated under these conditions for 72 hours. This allowed the researchers to demonstrate that immunotherapy treatment was effective in killing of the tumor only in the immune-enhanced patient tumor organoids, where the organoids without immune cells experienced no tumor death.

The technique for growing organoids has rapidly improved since the early 2010s and WFIRM has been at the forefront of this technology, said Shay Soker, PhD, a professor of regenerative medicine who leads the organoid biofabrication core at WFIRM.

"WFIRM scientists have successfully created organoids replicating most of the main organs of the body such as the liver, heart, brain and lung to screen drugs and model diseases, which can eliminate the need for animal testing," Soker said. "This method generates a 100 percent human experimental platform that recreates the interaction between host, tumor and immune system within 24 hours of obtaining the tissue specimen. It allows us to track the evolution of disease within the patient and potentially adjust the treatment based on the way the cancer changes over time."

WFIRM has partnered with the Comprehensive Cancer Center to establish the Wake Forest Organoid Research Center (WFORCE), a joint effort that brings together researchers and clinicians, like Soker and Votanopoulos, who co-direct the effort and are working side by side, to leverage the use of tissue organoid technologies for the benefit of patients.

The organoid platforms are a disruptive technology that could potentially save lives while also saving billions of dollars of taxpayer money and effect policy design. In 2017, the cost of health care in the US reached $3.5 trillion and is projected by the Centers for Medicare & Medicaid Services to reach $6 trillion by 2027. A portion of this cost is allocated in treating side effects from drugs that quite often have no meaningful activity for the patient.

Our genome consists of 20,000 genes, all of which may be capable of triggering disease. It is estimated that there are 7,000 unknown genes that cause recessive genetic diseases resulting from mutations in two copies of a gene that have been inherited from each parent. Researchers at the University of Geneva (UNIGE), Switzerland, have recently identified 45 new genes that cause blindness or cognitive problems. The scientists focused in particular on the SLC6A6 gene, which encodes a transporter protein that carries an amino acid essential for the functioning of the retina and cardiac muscle: taurine. When there are pathogenic mutations of the SLC6A6 gene, an individual will suffer from a lack of taurine and will gradually lose his sight until he becomes blind within a few years and develops a weak heart. The geneticists at the University of Geneva hypothesised that a taurine supplement might make it possible to compensate for this deficiency. The supplement was given to a young girl suffering from the disease to help stop the progression of her visual degeneration and to treat her cardiomyopathy. You can read all about this innovation in the treatment of recessive genetic diseases in the journal Human Molecular Genetics.

Recessive genetic diseases such as cystic fibrosis are the result of a mutation in the two copies of the same gene inherited from each parent. Researchers from UNIGE - working in collaboration with scientists from Pakistan - studied the genomes of 500 Pakistani families who had ill and healthy children in order to identify as many genes as possible that cause these conditions. "We looked at Pakistani families because consanguineous marriage is still a common practice, with 50% of marriages taking place between first cousins", explains Stylianos Antonarakis, emeritus professor in UNIGE's Faculty of Medicine. "In fact, consanguinity increases the risk of developing a recessive genetic disease since about 12% of the genome is identical in cousins."

New gene identified

One family was a source of particular interest to the researchers: the two parents - healthy first cousins - had four children, two of whom were sick: a 15-year-old boy, who lost all his sight in a few years, and a 4-year-old girl, who was gradually losing her sight but was still able to make out shapes and colours. "With the help of the Khyber Medical University in Pakistan, we collected blood samples of each family member. Their genome sequencing showed that their illness was linked to a mutation of the SLC6A6 gene", notes Muhammad Ansar, a researcher in the Genetics Department in UNIGE's Faculty of Medicine. This gene produces a protein of the cell membrane that transports taurine, an amino acid that is especially important for the functioning of the retina and cardiac muscle. "It's a dietary supplement found in large quantities in certain energy drinks", says Ansar. Patients suffering from the disease have extremely low levels of taurine in their blood. Professor Keith Henry of the University of North Dakota showed that the genetic abnormality in the family from Pakistan reduced the carrying capacity of taurine to 15% of its normal level.

A reversible recessive disease?

The scientists speculated that it might be possible to block the progression of the disease by administering taurine to the children. They brought the family to Geneva to conduct detailed investigations into this rare genetic disease. In addition to the progressive visual impairment, which was now unfortunately total in the case of the boy, the doctors diagnosed damage to the cardiac muscle in both children. The little girl fortunately still retained some residual vision.

Since taurine is a food supplement rather than a medicine, the Swiss Ethics Commission agreed that it could be administered orally. "We gave 100 mg per kg of taurine daily to the children to be continued over the long-term, and organised regular ophthalmologic and cardiac monitoring sessions in Pakistan", emphasises Emmanuelle Ranza, a doctor and geneticist at University Hospitals Geneva (HUG) and UNIGE who was responsible for the clinical part of the study. The results quickly came about: in three days, the taurine levels in their blood jumped from 6 to 85 μ mol/l, reaching normal thresholds. And, after two years, the cardiomyopathy had completely disappeared in both children! In addition, the degeneration in the girl's sight was brought to a halt, and there was even an improvement, meaning she could move around by herself. Unfortunately, this development was not possible for the boy, who had already lost his entire retina.

A single patient can change medicine

"These results are exceptional, because it's the first time a food supplement given orally has been used to treat the retina and the heart successfully", points out Antonarakis. "This little girl has paved the way for a potential cure for new-borns suffering from the same recessive disease. One patient can change the history of medicine!" In fact, researchers estimate that there are possibly 6,000 babies worldwide who might suffer from the same SLC6A6-related disease, and around 300 in Europe and North America. "Our goal now is to detect new-borns affected by the condition at an early stage so they can be treated from birth with a taurine supplement and potentially prevent the onset of symptoms", adds Antonarakis. The geneticists also aim to continue to identify new genes that cause recessive diseases, especially since they now have proof that some of them can be treated effectively.

Researchers have discovered ways to boost CAR T-cell therapy.

According to a study published in the Blood journal, drug profiling and the CRISPR-Cas9 gene editing method have opened new avenues in the development of CAR T-cell therapy, used to treat leukaemia and lymphoma.

The study, carried out collaboratively by the University of Helsinki and the Finnish Red Cross Blood Service, surveyed the effect of more than 500 cancer drugs on the function of CAR T cells.

CAR T-cell therapy has yielded excellent results in the case of certain blood cancers and lymphomas resistant to other forms of treatment. In CAR T-cell therapy, patient's own T cells (immune cells) are extracted from blood stream, after which they are engineered to express chimeric antigen receptors (CAR), which activate the cells to destroy cancer cells after identification.

"In spite of good treatment outcomes, the therapy is not effective in all patients. CAR T-cell therapy can also have adverse effects," says Professor Satu Mustjoki from the University of Helsinki.

The drug profiling highlighted a class of drugs known as SMAC mimetics, which in laboratory tests sensitised cancer cells to CAR T cells. At the same time, drugs that inhibit the function of CAR T cells were found, which have potential in the treatment of adverse effects.

By employing the CRISPR gene editing method, the researchers investigated which mechanisms impact the sensitivity of cancer cells to CAR T cells. A process known as death receptor signalling and the FADD gene required to initiate this process were found to be vital for CAR T-cell function. The CRISPR method also revealed that the mechanism of SMAC mimetics is based on the initiation of death receptor signalling.

Based on the test results, SMAC mimetics could potentially be used to further sensitise cancer cells to cell death caused by CAR T cells. If the promise of the drugs identified in the preliminary profiling is upheld by further research, SMAC mimetics could be utilised in improving the outcome of CAR T-cell therapy.

"The study provides an extensive dataset on the effect of cancer drugs on the function of T cells, which are essential to immunotherapies. This data can be put to use when planning the combination of cancer drugs with therapies activating the immune system," says doctoral candidate Olli Dufva from the University of Helsinki.

Women in low and medium-income countries struggle with many health issues in pregnancy and childbirth, but little attention is given to antenatal depression - which is on the rise in many developing countries, new PLOS ONE paper shows.

A study by Flinders University public health researchers found rising levels of reported antenatal depression in these countries, and recommends more services are urgently needed - particularly in low-income economies.

"Depression during pregnancy is often believed to be an issue of developed countries," says biostatistician Abel Fekadu Dadi, who led the systematic review and analysis of antenatal depression levels in low and middle-income countries.

"From the study, we found 34% and 22.7% of pregnant women in low and middle-income countries respectively had depression symptoms during pregnancy," says Mr Dadi, who is also affiliated with the Institute of Public Health at the University of Gondar, Ethiopia.

"Moreover, compared to non-depressed pregnant women, depressed women had respective rates of 2.41 times and 66% higher risk of preterm birth and low birth weight.

"We found that antenatal depression is highly prevalent and increases over the duration of pregnancy. We also noted increases in prevalence over the last 10 years."

Antenatal depression has detrimental effects on the physical, psychological, mental, and overall wellbeing of mothers and newborn babies, he says, stressing more must be done to raise awareness with health practitioners and policy-makers in developing economies.

"It is vital for these governments to address women's mental health issues before and during pregnancy to improve health outcomes for both mothers and babies, and contribute to socio-economic development and Sustainable Development Goals," says co-author Associate Professor Lillian Mwanri, from the Flinders College of Medicine and Public Health.

Key findings include:

One in three (34%) and one in five (22.7%) pregnant women in low-and middle-income countries, respectively had depression.

Having depression during pregnancy increased the risk of low birth weight and preterm births. Severe depression is known to directly lead to suicide in women during pregnancy or after birth - and to neonatal, infant and child mortality.

A poor obstetric history, previous episodes of common mental disorders, poor social support, financial difficulties, a history of exposure to violence (during pregnancy or earlier), and unsatisfactory relationships were factors that increased chances of depression.

Low-cost interventions such as psychotherapy services at maternity clinics - and relationship and partner support advice - are among the social and health system interventions badly needed in these countries.

What keeps most infectious disease researchers up at night aren't infamous viruses like Ebola. Instead, influenza, commonly known as the flu, continues to be a clear and present danger to humanity.

"Influenza is a huge problem, as the virus sickens or kills millions of people each year," says David Markovitz, M.D., professor of internal medicine in the division of infectious diseases at Michigan Medicine. "A new pandemic along the lines of the 1918 Spanish flu has the potential to kill millions here and abroad."

To that end, he and an extensive team of collaborators have worked for years on broad-spectrum antiviral drugs developed from, of all things, banana plants.

In a new paper published in the Proceedings of the National Academy of Sciences, Markovitz, first author Evelyn Coves-Datson, a M.D., Ph.D. student, Akira Ono, Ph.D., professor of microbiology and immunology and their team have shown that an engineered compound based on a banana lectin, a protein called H84T, has real potential for clinical use against influenza.

In their experiments, more than 80% of mice exposed to a form of influenza that is typically fatal were able to survive the disease after receiving an injection of the protein, even up to 72 hours after exposure.

The team also provides early evidence that the compound is safe. A downside of naturally occurring banana lectin--which can cause inflammation by inappropriately activating the immune system--wasn't present in mice given H84T. Furthermore, because H84T is a protein, there was concern that the body would recognize it as foreign and develop antibodies against it, thereby neutralizing it or causing harm. The team found that while mice did develop antibodies against H84T, they didn't appear to be adversely affected by them.

The compound works because it targets a sugar called high mannose, which is present on the outside of certain viruses but not on most healthy cells. "We were able to show that H84T blocks the ability of the influenza virus to fuse with structures termed endosomes in the human cell, a key step in infection," he explains. Doing so disabled their ability to replicate and wreak havoc.

Amazingly, this mechanism of action, binding of high mannose sugars on the surface of viruses, means that H84T is effective not only against influenza, but also against Ebola, HIV, measles, MERS, a new deadly viral illness that was first reported in Saudi Arabia in 2012, SARS and all other coronaviruses tested.

Even more promising is that the compound works where Tamiflu (oseltamivir), the current standard therapy for severe flu, has failed. "We've also shown that there may be a synergistic effect between H84T and Tamiflu," says Markovitz.

His team hopes to do more research with the compound in humans in the hopes of getting it to market. "We envision the government potentially stockpiling it in the event of a pandemic." However, he says, "there are many difficulties to commercialization. Pharmaceutical economics do not seem to favor the development of antivirals or antibacterials for one-time usage, which is a huge problem."

A team led by Professor Kaat Alaerts (KU Leuven) recruited 40 adult men with autism spectrum disorder to take part in their study.

"In a first stage, we examined the amount of oxytocin produced by the participants themselves. The subjects also filled out several questionnaires," Professor Alaerts explains. "An analysis of the data revealed that the amount of oxytocin found in the subjects' saliva was inversely related to their self-reported attachment issues."

In a second stage of the research, the team examined the long-term effects of administering oxytocin through a nasal spray. This experiment produced remarkable results: the participants who had been given oxytocin for four weeks experienced positive effects until up to a year later.

Less repetition, more attachment

"We divided the 40 participants into an experimental group and a control group. The control group received a placebo for four weeks," says doctoral student Sylvie Bernaerts, who is the first author of the study in Molecular Autism.

"Over the course of a full year, we also asked the participants to fill out questionnaires on four different occasions. These questionnaires were used to examine the impact of the oxytocin-containing nasal spray on the symptoms of autism."

In terms of social interaction, the researchers found no difference between the experimental group and the control group. But for repetitive behaviour (including the need for routines) and attachment, the results were significant: "The people in the experimental group reported far less repetitive behaviour and also reported fewer problems with forming close relationships."

This study shows for the first time what the long-term effects are of repeatedly administering oxytocin to people with autism. Professor Alaerts: "Participants who took oxytocin every day for four weeks experienced positive effects until up to a year later. That's a remarkable result."

Further research necessary

For this study, the scientists only selected male participants. This was partly because autism is more prevalent in men, and women's hormonal cycle may influence the test results. Furthermore, oxytocin is already being used to induce labour or breastfeeding in pregnant women or women who have recently given birth, respectively. In other words, there are more factors to take into account in female test subjects.

And what about using oxytocin as a treatment? "As oxytocin is already being used in medicine, you might think that we can start using it quite soon to address attachment issues or to reduce repetitive behaviour in people with autism," says Professor Alaerts. But she is quick to temper expectations: "The findings we're presenting today are the result of a first pilot study. A lot of further research needs to be done before oxytocin can be used to treat people with autism."

PROVIDENCE, R.I. [Brown University] -- A new study analyzing the first 1,000 participants in the Rhode Island Consortium for Autism Research and Treatment (RI-CART) identifies key trends in the presentation and diagnosis of autism spectrum disorder. The study was published in Autism Research on Monday, Jan. 20.

The first finding was that girls with autism receive a diagnosis, on average, nearly 1.5 years later than boys. This is likely because parents and clinicians tend to notice language delays as the first sign of autism, and girls in the study exhibited more advanced language abilities compared to boys, said study authors Stephen Sheinkopf and Dr. Eric Morrow.

Autism is far more common in boys. The RI-CART study found more than four times as many boys as girls with autism; however, given the large size of the sample, the study was well-powered to evaluate girls with autism. The finding that girls with autism are diagnosed later is clinically important, said Morrow, an associate professor of molecular biology, neuroscience and psychiatry at Brown University.

"The major treatment that has some efficacy in autism is early diagnosis and getting the children into intensive services, including behavioral therapy," Morrow said. "So if we're identifying girls later, that may delay their treatments."

Sheinkopf, an associate professor of psychiatry and pediatrics at Brown, emphasized the importance of early recognition.

"We need to think about how we can improve recognition of autism in individuals -- including many of these girls -- who don't have the same level of primary language delay but may have other difficulties in social communication, social play and adapting to the social world," he said. "And as we improve diagnosis for the full range of individuals in the early years, we must also rethink early interventions to make sure they're designed appropriately for children who might need assistance on more nuanced elements of social adaptation. We need to refine treatments so they cater to individual needs."

Based at Bradley Hospital in East Providence, the team behind RI-CART represents a public-private-academic collaborative -- a partnership between researchers at Brown, Bradley Hospital and Women and Infants -- that also involves nearly every site of service for families affected by autism in Rhode Island. The study team also integrated members of the autism community, family members and particularly the Autism Project, a family support service for autism in the state.

By engaging both the community and treatment providers, the study enrolled more than 20 percent of pediatric-age individuals with autism in Rhode Island. Participants were recruited from all geographic regions of the state, and as part of the study, they were given rigorous in-person assessments.

Most participants had received an autism diagnosis prior to entering the study (a community diagnosis), and their diagnosis was subsequently confirmed by an in-person assessor, meaning that they also received a research diagnosis. The study also included individuals whose diagnoses were less clear cut. For example, some individuals received either a community diagnosis or a research diagnosis, but not both. Other individuals were referred to the study but did not have evidence of autism from either a community evaluation or the research assessment.

"The group that was diagnostically less clear-cut represents the complexity that clinicians encounter on a daily basis, so it's a realistic sample in that sense," Sheinkopf said. "This full range of heterogeneous autism presentation is rather unique to our study."

The other major finding of the study was that people with autism frequently exhibit co-occurring psychiatric and medical conditions.

Nearly half of the participants reported another neurodevelopmental disorder (i.e., attention-deficit/hyperactivity disorder (ADHD) or intellectual disability), while 44.1 percent reported a psychiatric disorder, 42.7 percent reported a neurological condition (i.e., seizures/epilepsy, migraines, tics), 92.5 percent reported at least one general medical condition and nearly a third reported other behavioral problems.

"These co-occurring conditions need also to be a focus of treatment for patients," Morrow said.

"Many people with autism need support for the psychiatric and emotional challenges that are prevalent in people who share this one diagnosis," Sheinkopf added. "These are clinically complicated individuals who deserve strong, sophisticated, multidimensional, multidisciplinary care."

Sheinkopf and Morrow say they're encouraged by the support and collaboration of a variety of health care providers, community members and particularly, by the level of commitment shown by the families who participated in the study. Going forward, they're hopeful that the RI-CART registry will lead to more studies that will improve the lives of people with autism and their families, particularly because the cohort currently involves such a wide age range of participants, including individuals with autism ages 2 to nearly 64.

"Given that autism is a developmental disorder, the field really needs to focus on longitudinal studies: following people's development and transitions," Morrow said. "I think we're going to learn even more when we follow children from a very young age as they develop, including into adulthood."

Despite the protections in place to support breastfeeding for employees, the burden still falls on working mothers to advocate for the resources they need, according to a new study from the University of Georgia.

The study also revealed gaps in the quality and accessibility of breastfeeding resources in the eyes of working mothers.

"We know that there are benefits of breastfeeding for both the mother and the infant, and we know that returning to work is a significant challenge for breastfeeding continuation," said Rachel McCardel, a doctoral student at UGA's College of Public Health and lead study author.

"There is a collective experience that we wanted to explore and learn how can we make this better."

McCardel and her co-author specifically wanted to better understand breastfeeding support in the workplace since federal guidelines went into place over a decade ago requiring employers to provide unpaid break time and a space other than a restroom for employees to be able to express breast milk.

For their study, McCardel's team surveyed female employees who performed a variety of jobs.

In addition to asking questions about their access to breastfeeding resources like private rooms, breast pumps and lactation consultants, the respondents were also asked about their experiences with combining breastfeeding and work.

They found that most respondents, nearly 80%, had a private space at work to express milk, and around two-thirds of the women reported having break times to breastfeed. Access to other resources like lactation consultants or breast pumps was less common.

Many respondents also said they hadn't expected to get much help from their employers, and there was a general lack of communication about the resources available to them.

That's a small fix that employers could implement today, said Heather Padilla, an assistant professor at the College of Public Health and study co-author.

"Designate a person who is responsible for making sure that women who are preparing for the birth of their baby understand what resources they have available to them when they return to work," she said. This could be a supervisor, an HR director or a mentor, she added.

Care and support for employees should extend to breastfeeding support, said McCardel.

"According to the most recent Workplace Health in America Survey, we're now seeing about 46% of worksites are offering some sort of health promotion programming, but only 8% offer lactation resources," she said. "I feel like that's a missed opportunity because it's a crucial part of work-life balance, especially for new mothers."

Padilla said, "Employers who want to keep valued employees should think about how to create a workplace that considers the challenges that working mothers face."

"Many women who have young children are in the workforce, and we should be able to make it easier for them to combine those two things," said Padilla. "It shouldn't be a choice of one or the other."

Boston - High blood pressure (BP) affects more than 150 million adults in the United States, putting them at increased risk for a range of health problems, including heart attack and stroke. Because salt consumption is thought to contribute to high blood pressure by stimulating thirst and leading to greater fluid intake, cutting salt intake is widely considered to be an important strategy for lowering blood pressure. Separately, recent studies have suggested that higher sodium intake does not in fact stimulate thirst and fluid intake but promotes weight loss by changing the body's total energy needs.

A new study led by Stephen Juraschek, MD, PhD, Assistant Professor of Medicine at Beth Israel Deaconess Medical Center (BIDMC), sheds new light on these conflicting findings. The researchers found that reducing sodium intake in adults with elevated blood pressure or hypertension decreased thirst, urine volume (a marker of fluid intake), and blood pressure, but did not affect metabolic energy needs. These results, published in the journal Hypertension, support the traditional notion that decreasing sodium intake is critical to managing hypertension - disputing recent studies.

Using data from the completed Dietary Approaches to Stop Hypertension (DASH)-Sodium trial, a randomized controlled-feeding study, published in 2001, the researchers examined the effects of three different levels of sodium intake (low, medium, and high) on blood pressure in participants following two distinct diets - a typical American diet (control diet) or a healthy diet (the DASH Diet). In this secondary analysis of the DASH-Sodium trial, the researchers measured the impact of sodium intake on participants' energy intake, weight, self-reported thirst, and 24-hour urine volume.

The researchers found that, while reduced sodium intake did not affect the amount of energy required to maintain a stable weight, it did decrease participants' thirst. Furthermore, urine volume was either unchanged or lower with reduced sodium intake. Together these results suggest that in adults with elevated blood pressure or hypertension, a lower sodium intake decreases thirst, urine volume (and likely fluid intake) and blood pressure. These changes occurred without altering the amount of energy required to keep body weight constant.

"Our study contributes meaningfully to this scientific debate and underscores the importance of sodium reduction as a means to lower blood pressure," said Juraschek. "Public health recommendations aimed at lowering population-wide sodium intake for blood pressure should continue without fear of contributing to weight gain."

As a next step, Juraschek and his colleagues plan to continue to study the effects of sodium over a longer duration in adults with diabetes, as well as look at the effects of fluid intake on clinical outcomes through clinical trials as well as in large national datasets such as the National Health and Nutrition Examination Survey (NHANES).