Body

Researchers led by Takeo Yoshikawa at the RIKEN Center for Brain Science in Japan have discovered a biomarker that can detect autism spectrum disorder (ASD) in preschool-aged children. Published in Brain Communications, the new study found that levels of the protein FABP4 were much lower in four- to six-year-old children with ASD than they were in other typically developing children. Experiments in mice that lacked FABP4 revealed changes in neurons that resemble those found in the postmortem brains of people with ASD.

ASD is a developmental disorder that begins in early childhood and affects learning, communication, and social behavior. The severity of symptoms falls on a broad spectrum, which researchers believe is related to genetic and environmental factors that interact during brain development. Because young children with ASD are at particular risk for being overweight, the RIKEN CBS group hypothesized a link between ASD and fat-cell metabolism.

Fat cells make hundreds of important biomolecules called adipokines, some of which regulate brain activity. The researchers took blood samples from preschool-aged children with and without ASD and compared their adipokine levels. The team examined adipokines known to be associated with ASD as well as the protein FABP4. "We previously found lower levels of FABP4 in the hair follicles of patients with schizophrenia," explains first author Motoko Maekawa. "Although the disorders themselves are very different, we knew that FABP4 was an adipokine that can modulate brain function, especially during development."

The researchers found that preschool-aged children with ASD had much lower levels of FABP4 in their blood than other children did, but that other adipokines did not differ between groups. A second test in two other groups of children confirmed these results. This makes FABP4 a potential early biomarker for ASD. "The identification of FABP4 as a biomarker that can detect ASD in four- to -six-year old children is good news," says Maekawa, "especially because early diagnosis and intervention can lead to better long-term prognosis."

Further analysis showed that the story is a little more complex. Similar comparisons in older children and in postmortem brains showed equal levels of FABP4 between ASD and non-ASD groups. This means that FABP4 levels differ during a critical period during brain development, making it more than just a biomarker. Its lack could be a factor that leads to the disease, rather than being just a byproduct.

To confirm the importance of FABP4, the researchers created knockout mice that lacked the FABP4 gene. Compared with wildtype mice, behavior testing showed that these mice interacted less with unknown mice and had more difficulty with spatial learning and memory, all reminiscent of difficulties shared by those with ASD. Additionally, when the team examined the neurons in the mouse brains, they found shape and structural characteristics that match those found in postmortem brains from people with ASD.

Looking forward, there are three questions that the researchers hope to answer. "We hope to replicate our findings in a larger group, which will allow us to determine whether specific ASD symptoms or their severity are related to low levels of FABP4," says Maekawa. "We also hope to conduct a prospective cohort study of newborns to determine if FABP4 levels at birth can predict the future manifestation of ASD."

Lastly, the researchers will continue studying the FABP4 mouse model of ASD to understand exactly how the FABP4 protein affects the developing brain.

A recent study examining pain among cannabis users suggests that--unlike long-term opioid use--regular cannabis use does not appear to increase pain sensitivity.

Doctoral student Michelle St. Pierre, who conducts research in the psychology department at UBC Okanagan, recently published a study looking for differences in pain tolerance of people who frequently use cannabis compared to those who don't.

"Recent years have seen an increase in the adoption of cannabinoid medicines, which have demonstrated effectiveness for the treatment of chronic pain," says St. Pierre. "However, the extent to which frequent cannabis use influences sensitivity to acute pain has not been systematically examined."

Interest in the use of cannabinoids to help with chronic pain relief has accelerated over the past decade, St. Pierre explains, noting that a recent survey of medical cannabis patients reported that more than half used cannabis for pain relief. That's despite recent reviews which suggest the effectiveness of cannabinoid therapies for chronic pain is mixed.

"This study should come as good news to patients who are already using cannabis to treat pain," says co-author Zach Walsh, who leads the UBC Therapeutic Recreational and Problematic Substance Use Lab which hosted the study. "Increases in pain sensitivity with opioids can really complicate an already tough situation; given increasing uptake of cannabis-based pain medications it's a relief that we didn't identify a similar pattern with cannabinoids."

St. Pierre's study explored differences in measures of pain intensity and tolerance. The authors speculated that people who report frequent cannabis use would demonstrate greater experimental pain sensitivity but instead found no differences.

"There is a different effect from opioid users; sustained use of opioids can make people more reactive to pain. We wanted to determine if there was a similar trend for people who use cannabis frequently," says St. Pierre. "Cannabis and opioids share some of the same pain-relief pathways and have both been associated with increases in pain sensitivity following acute use."

The risk of addiction, overdose and opioid-induced hyperalgesia--where someone becomes more sensitive to pain--are major issues when it comes to using opioids to manage chronic pain, St. Pierre says. A patient with hyperalgesia might then increase their dosage of the opioid to manage the pain, further increasing the risk of addiction.

The analgesic effects of cannabis have been proposed to engage some of the similar brainstem circuitry to those of opioids. However, the extent to which cannabinoids induce hyperalgesia has not been determined.

For her study, St. Pierre recruited volunteers who used cannabis more than three times a week and people who didn't use it at all. Study participants were subjected to a cold-pressor task test, where they submerged a hand and forearm in icy water for a sustained amount of time.

What they determined was that cannabis use doesn't carry the same risk for hyperalgesia that opioid use does, she adds.

"Our results suggest frequent cannabis use did not seem to be associated with elevated sensitivity to experimental pain in a manner that can occur in opioid therapy," she says. "This is an important distinction that care providers and patients should consider when selecting options for pain management. These findings are particularly relevant in light of recent reports of opioid overprescribing and high rates of pain in the population, as it suggests that cannabis may not carry the same risk of hyperalgesia as opioids."

BOSTON - The death of a family pet can trigger a sense of grief in children that is profound and prolonged, and can potentially lead to subsequent mental health issues, according to a new study by researchers at Massachusetts General Hospital (MGH). In a paper appearing in European Child & Adolescent Psychiatry, the team found that the strong emotional attachment of youngsters to pets might result in measurable psychological distress that can serve as an indicator of depression in children and adolescents for as long as three years or more after the loss of a beloved pet.

"One of the first major losses a child will encounter is likely to be the death of a pet, and the impact can be traumatic, especially when that pet feels like a member of the family," says Katherine Crawford, CGC, previously with the Center for Genomic Medicine at MGH, and lead author of the study. "We found this experience of pet death is often associated with elevated mental health symptoms in children, and that parents and physicians need to recognize and take those symptoms seriously, not simply brush them off."

Roughly half of households in developed countries own at least one pet. And as the MGH investigators reported, the bonds that children form with pets can resemble secure human relationships in terms of providing affection, protection and reassurance. What's more, previous studies have shown that children often turn to pets for comfort and to voice their fears and emotional experiences. While the increased empathy, self-esteem and social competence that often flow from this interaction is clearly beneficial, the downside is the exposure of children to the death of a pet which, the MGH study found, occurs with 63 percent of children with pets during their first seven years of life.

Prior research has focused on the attachment of adults to pets and the consequences of an animal's death. The MGH team is the first to examine mental health responses in children. Their analysis is based on a sample of 6,260 children from the Avon Longitudinal Study of Parents and Children (ALSPAC), in Bristol, England. This population-based sample is replete with data collected from mothers and children that enabled researchers to track the experience of pet ownership and pet loss from a child's early age up to eight years.

"Thanks to this cohort, we were able to analyze the mental and emotional health of children after examining their experiences with pet death over an extended period," notes Erin Dunn, ScD, MPH, with the MGH Center for Genomic Medicine and Department of Psychiatry, and senior author of the study. "And we observed that the association between exposure to a pet's death and psychopathology symptoms in childhood occurred regardless of the child's socio-economic status or hardships they had already endured in their young lives."

Researchers also learned that the relationship between pet death and increased psychopathology was more pronounced in male than female children -- a finding that surprised them in light of prior research -- and that the strength of the association was independent of when the pet's death occurred during childhood, and how many times or how recently it occurred. According to Dunn, this latter finding speaks to "the durability of the bond with pets that is formed at a very early age, and how it can affect children across their development."

The MGH study stressed the importance of parents, caregivers and pediatricians recognizing and taking seriously the short- and long-term psychological reactions of children to the death of a pet - reactions which can mimic a child's response to the loss of other important family members. "Adults need to pay attention to whether those feelings are deeper and more profound and if they're lasting longer than might have been expected," says Crawford. "They could be signs of complicated grief and having someone to talk to in a sympathetic or therapeutic way may be extremely helpful for a child who is grieving."

Atypical teratoid rhabdoid tumors (ATRT) are a rare, fast-growing form of brain cancer that usually strikes children three years and younger, though they can occur in older children and adults. There are multiple treatments, but no definitive standard of care and long-term survival is poor.

The cause of ATRT is primarily linked to inactivation of a gene called SMARCB1, part of a larger complex that helps regulate gene expression and developmental processes. In a study published online September 10, 2020 in the journal Genes & Development, an international team of scientists, led by researchers at University of California San Diego School of Medicine and the San Diego Branch of the Ludwig Institute for Cancer Research, describe how the loss of the gene negatively impacts neural development and promotes tumor growth.

"Previous research has established that, unlike some cancers, ATRT is predominantly associated with the functional loss of a single gene -- SMARCB1 -- which leads to tumor development through changes in how genes are expressed rather than the combined effect of multiple gene mutations," said senior author Frank Furnari, PhD, professor of pathology and Ludwig San Diego member.

"ATRT is a very deadly cancer with very few effective therapies, which are complicated by the negative effects of radiation upon the child's cognitive development. We need targeted therapeutics and to create those, we need to better understand the mechanisms driving ATRT."

Led by Furnari and first author Alison Parisian, a graduate student in Funari's lab, the team prompted the loss of SMARCB1 in human induced pluripotent stem cells, then directed the iPSCs to develop into neurons or into cerebral organoids -- complexes of diverse nerve cells and glia that mimic functional aspects of the developing brain in miniature.

In doing so, they identified an interaction between the loss of SMARCB1 and neural differentiation pressure, which resulted in both a resistance to final differentiation and a defect in maintaining normal cell health that showed similarity to patient tumors.

"With this new information in hand," said Parisian, "our plan is to use our ATRT model and look for therapeutic targets that will cause these tumors to fully differentiate and therefore stop growing, which could prove to be an effective future therapy for ATRT."

Jupiter's moons are hot.

Well, hotter than they should be, for being so far from the sun. In a process called tidal heating, gravitational tugs from Jupiter's moons and the planet itself stretch and squish the moons enough to warm them. As a result, some of the icy moons contain interiors warm enough to host oceans of liquid water, and in the case of the rocky moon Io, tidal heating melts rock into magma.

Researchers previously believed that the gas giant Jupiter was responsible for most of the tidal heating associated with the liquid interiors of the moons, but a new study published in Geophysical Research Letters found that moon-moon interactions may be more responsible for the heating than Jupiter alone.

"It's surprising because the moons are so much smaller than Jupiter. You wouldn't expect them to be able to create such a large tidal response," said the paper's lead author Hamish Hay, a postdoctoral fellow at the Jet Propulsion Laboratory in Pasadena, California, who did the research when he was a graduate student in the University of Arizona Lunar and Planetary Laboratory.

Understanding how the moons influence each other is important because it can shed light on the evolution of the moon system as a whole. Jupiter has nearly 80 moons, the four largest of which are Io, Europa, Ganymede and Callisto.

"Maintaining subsurface oceans against freezing over geological times requires a fine balance between internal heating and heat loss, and yet we have several pieces of evidence that Europa, Ganymede, Callisto and other moons should be ocean worlds," said co-author Antony Trinh, a postdoctoral research fellow in the Lunar and Planetary Lab. "Io, the moon closest to Jupiter, shows widespread volcanic activity, another consequence of tidal heating, but at a higher intensity likely experienced by other terrestrial planets, like Earth, in their early history. Ultimately, we want to understand the source of all this heat, both for its influence on the evolution and habitability of the many worlds across the solar system and beyond."

Tidal Resonance

The trick to tidal heating is a phenomenon called tidal resonance.

"Resonance creates loads more heating," Hay said. "Basically, if you push any object or system and let go, it will wobble at its own natural frequency. If you keep on pushing the system at the right frequency, those oscillations get bigger and bigger, just like when you're pushing a swing. If you push the swing at the right time, it goes higher, but get the timing wrong and the swing's motion is dampened."

Each moon's natural frequency depends on the depth of its ocean.

"These tidal resonances were known before this work, but only known for tides due to Jupiter, which can only create this resonance effect if the ocean is really thin (less than 300 meters or under 1,000 feet), which is unlikely," Hay said. "When tidal forces act on a global ocean, it creates a tidal wave on the surface that ends up propagating around the equator with a certain frequency, or period."

According to the researchers' model, Jupiter's influence alone can't create tides with the right frequency to resonate with the moons because the moons' oceans are thought to be too thick. It's only when the researchers added in the gravitational influence of the other moons that they started to see tidal forces approaching the natural frequencies of the moons.

When the tides generated by other objects in Jupiter's moon system match each moon's own resonant frequency, the moon begins to experience more heating than that due to tides raised by Jupiter alone, and in the most extreme cases, this could result in the melting of ice or rock internally.

For moons to experience tidal resonance, their oceans must be tens to hundreds of kilometers - at most a few hundred miles - thick, which is in range of scientists' current estimates. However, there are some caveats to the researchers' findings.

Their model assumes that tidal resonances never get too extreme, Hay said. He and his team want to return to this variable in the model and see what happens when they lift that constraint.

Hay also is hoping that future studies will be able to infer the true depth of the oceans within these moons.

Systematic efforts and a clear structure are decisive factors in the transition to person-centred health care. A University of Gothenburg study, published in the scientific journal BMJ, reflects what is now a decade of experience and research in the field.

Expectations are growing stronger for health care to be person-centered, and therefore emanate from a partnership between staff, patients and relatives. But at the same times, the process of introducing and maintaining this way of working is slow and laborious in many places.

We already know that person-centred care can shorten hospital stay and reduce uncertainty in health care. Now, instead, we need to concentrate on how to achieve it, the researchers behind the broad BMJ article argue.

The study offers advice and tools for further research on, and development of, person-centred care. The corresponding author is Axel Wolf, Associate Professor of Health Care Sciences at the Institute of Health and Care Sciences at the Sahlgrenska Academy, University of Gothenburg. Axel Wolf is also affiliated to the University of Gothenburg Centre for Person-centred Care (GPCC).

"One of the key pieces of advice is that person-centred care must be practiced systematically on an everyday basis. This entails creating the organisational and individual conditions for developing a partnership between the patient, the patient's relatives if applicable, and the staff at every meeting -- not just when it fits into the schedule," Wolf says.

"To achieve the best clinical effect, it is important for person-centred care not to be just a matter between the patient and the individual professional representative. It has to permeate the whole organisation. There is also a big challenge involved in increasing the understanding of how person-centred care differs from current care practice."

It is fundamental for health care professionals to take the time to listen to what patients have experienced and wants to achieve in relation to their health. They must let the patient's goals, such as returning to work or being able to take a walk, guide the wording of a jointly agreed health plan. The patient's priorities and resources must be reflected in the health-plan, which must also be subject to continuous evaluation. The documentation must then accompany and be accessible to the patient, and this includes any move from hospital to primary care or municipal social care.

Since it set out ten years ago GPCC, a national research centre, has led the way in developing, testing, evaluating and implementing person-centred care in many different health care contexts, in Sweden and abroad.

Together with his colleague Professor Nicky Britten of the University of Exeter in England, Axel Wolf has lead an international research group investigating the enablers and the obstacles experienced by researchers, clinicians, and patients during clinical studies within the GPCC framework, and in everyday implementation of research results.

Among the obstacles described in the current study are hierarchical care structures, rigid occupational roles, and the conviction that one is already working in a person-centred way.

"With the current shift in Swedish health care to "good quality local health care", which is permeated by person-centred principles, the ethical approach focusing on the person and not only the diagnosis must be practiced constantly to optimize conditions. This requires systematic education and training, lifelong learning, and tools that facilitate the partnership," Axel Wolf concludes.

BOSTON - A portable, low-field magnetic resonance imaging (MRI) device can be safely used at bedside in complex clinical care settings to evaluate critically-ill patients for suspected stroke, traumatic brain injury (TBI), or other neurological problems, results of a proof-of-concept study show.

"How can a portable low-field device that operates on a standard electrical plug change the paradigm? It can bring the MRI to the bedside, and it can do so in a hospital environment where there is metallic material nearby, and can do it safely because the magnetic field strength is lower," says W. Taylor Kimberly, MD, PhD, chief of the division of Neurocritical Care at Massachusetts General Hospital (MGH).

Among 30 patients in a the Yale Neuroscience intensive care unit (ICU), the bedside MRI system produced important neuroimaging findings in 29, and the findings jibed with conventional radiology findings in all but one case, found Kimberly, Matthew S. Rosen, PhD, director of the Low Field MRI and Hyperpolarized Media Lab and co-Director of the Center for Machine Learning at the Athinoula A. Martinos Center for Biomedical Imaging at MGH, and colleagues at Yale University in New Haven, Connecticut.

In addition, the bedside MRI detected abnormal neurologic findings in eight of 20 patients with altered mental status in a COVID-19 ICU.

The investigators report their finding online in the journal JAMA Neurology.

MRI is unparalleled as an imaging technology for detecting disease or injury to the brain and central nervous system, but traditional MRI units are immobile behemoths containing large, heavy magnets made of super-conducting material that requires super-cooling with liquid nitrogen or helium. In addition, the high magnetic field strengths of standard MRI units - 1.5 to 3 Tesla - require careful screening of patients to ensure that there are no ferrous metals in or on their bodies (such as medical implants, insulin pumps, or shrapnel fragments) that could cause serious injury during imaging, and any medical equipment containing ferromagnetic components must be kept out of the MRI room.

In contrast, the mobile MRI system trades some of the high-resolution imaging quality of a fixed MRI for portability and lower cost. The device contains a 0.064 Tesla permanent magnet that does not require cooling, and can be plugged into a single 110 volt, 15 amp outlet, making it suitable for use in settings such as emergency departments, mobile stroke units, and regions with limited medical resources. The lower strength magnetic field does not interfere with metal-containing equipment in patient care units.

The system grew out of work Rosen began more than a decade ago at the request of the U.S. Department of Defense (DoD). DoD staff were concerned that soldiers with battlefield injuries might have shrapnel in their heads that could cause serious injury or death if they were placed into a high-field scanner.

"This is an enabling technology to bring non-invasive neuroimaging with the soft-tissue contrast and all of those things neurologists have been relying on for years to environments where it otherwise would not be possible," Rosen says.

The Earth's magnetic field is trapping high energy particles. When the first satellites were launched into space, scientists led by James Van Allen unexpectedly discovered the high energy particle radiation regions, which were later named after its discoverer Van Allen Radiation Belts. Visualized, these look like two donut-shaped regions encompassing our planet.

Now, a new study led by researchers from GFZ German Research Centre for Geosciences shows that electrons in the radiation belts can be accelerated to very high speeds locally. The study shows that magnetosphere works as a very efficient particle accelerator speeding up electrons to so-called ultra-relativistic energies. The study conducted by Hayley Allison, a postdoctoral scholar at GFZ Potsdam, and Yuri Shprits from GFZ and Professor at the University of Potsdam, is published in Nature Communications.

To better understand the origin of the Van Allen Belts, in 2012 NASA launched the Van Allen Probes twin spacecraft to traverse this most harsh environment and conduct detailed measurements in this hazardous region. The measurements included a full range of particles moving at different speeds and in different directions and plasma waves. Plasma waves are similar to the waves that we see on the water surface, but are in fact invisible to the naked eye. They can be compared to ripples in the electric and magnetic field.

Recent observations revealed that the energy of electrons in the belts can go up to so called ultra-relativistic energies. These electrons with temperatures above 100 Billion degrees Fahrenheit, move so fast that their energy of motion is much higher than their energy of rest given by Einstein's famous E=mc2 formula. They are so fast that the time flow significantly slows down for these particles.

Scientists were surprised to find these ultra-relativistic electrons and assumed that such high energies can be only reached by a combination of two processes: the inward transport of particles from the outer regions of the magnetosphere, which accelerates them; and a local acceleration of particles by plasma waves.

However, the new study shows that electrons reach such incredible energies locally, in the heart of the belts, by taking all this energy from plasma waves. This process turns out to be extremely efficient. The unexpected discovery of how acceleration of particles to ultra-relativistic energies operates in the near-Earth space, may help scientists understand the fundamental processes of acceleration on the Sun, near outer planets, and even in the distant corners of the universe where space probes cannot reach.

As children with chronic rheumatic illnesses age, it's important that they experience a smooth transition from pediatric to adult care. A study published in Arthritis Care & Research has identified certain factors that are important during this time.

In the study of 141 pediatric patients who transferred to an adult rheumatology clinic, continued insurance coverage and referral from a pediatric rheumatologist decreased delays in attending an adult rheumatology visit.

Pediatric patients with connective tissue diseases (such as lupus) or of Black race were especially vulnerable to unscheduled hospitalizations and emergency department visits following the transfer to adult care.

"The majority of patients in this study had public or no insurance during their pediatric course. It is especially important to ensure that vulnerable transition-age patients have a plan for insurance coverage and an identified adult rheumatologist prior to the transfer to adult care," said lead author Nicole Bitencourt, MD, of UT Southwestern Medical Center. "It may be helpful for pediatric rheumatologists to have a system in place to ensure patients are not lost to follow up before establishing care with an adult rheumatologist."

In France, antiretroviral treatment (ARV) can be dispensed by hospitals and/or community pharmacies. A recent study published in Pharmacology Research & Perspectives examined the pharmacist's role in HIV care in this country.

For the study, 2 national surveys were sent. The first was an anonymous questionnaire for people living with HIV, and the second was an online survey for community and hospital pharmacies. A total of 1,137 people living with HIV and 246 pharmacies responded.

The surveys pertained to medication interviews with pharmacists during ARV dispensing, where patients could receive explanations about efficacy and tolerance, recommendations for proper use of their medication, and advice about any drug interactions. The surveys also pertained to online patient medication files. When these files are offered by pharmacists and accepted by patients covered by health insurance, they can be used to record all the drugs dispensed during the previous four months. A patient's file thus constitutes a tool for coordinating prescriptions, generating advice, and identifying precautions in the use of different medications.

While the existence of the online medication file was known by 58% of people living with HIV, only 40% of pharmacists declared it to be systematically offered. It was offered to 17% of people living with HIV, and 80% of those people accepted it. Only 7% of people living with HIV felt well taken care of because they were offered medication interviews, but 32% said they would like to take advantage of this program. The results suggest the need for better implementation of medication files and interviews.

Just a single exercise workout has positive effects on learning and memory in young adults, according to a recent review of published studies.

The review, which is published in Translational Sports Medicine, included 13 relevant studies. The types of exercise that were studied involved walking, running, and bicycling in individuals between 18 to 35 years of age.

Investigators found that aerobic exercise for 2 minutes to 1 hour at moderate to high intensity improved attention, concentration, and learning and memory functions for up to 2 hours. They noted that the results may have important education-related implications.

"Exercise makes you smart," said co-author Peter Blomstrand, MD, PhD, of County Hospital Ryhov and Jönköping University, in Sweden.

DALLAS, Sept. 9, 2020 -- Drinking eight or more alcoholic beverages a week may increase the risk of high blood pressure (also called hypertension) among adults with Type 2 diabetes, according to new research published today in the Journal of the American Heart Association, an open access journal of the American Heart Association.

"This is the first large study to specifically investigate the association of alcohol intake and hypertension among adults with Type 2 diabetes," said senior study author Matthew J. Singleton, M.D., M.B.E., M.H.S., M.Sc., chief electrophysiology fellow at Wake Forest University School of Medicine in Winston-Salem, North Carolina. "Previous studies have suggested that heavy alcohol consumption was associated with high blood pressure, however, the association of moderate alcohol consumption with high blood pressure was unclear."

Researchers examined the relationship between alcohol consumption and blood pressure in more than 10,000 adults with Type 2 diabetes (average age 63, 61% male). All were participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, one of the largest, long-term trials to compare different treatment approaches to reduce heart disease risk in adults with Type 2 diabetes, conducted from 2001-2005 at 77 centers across the U.S. and Canada.

All participants had Type 2 diabetes for an average of 10 years prior to enrolling in the study. In addition to 10 years with Type 2 diabetes, they were at increased risk for cardiovascular events because they had pre-existing cardiovascular disease; evidence of potential cardiovascular disease; or had at least two additional cardiovascular disease risk factors (such as high blood pressure, high cholesterol, smoking, or obesity).

In this study, alcohol consumption was categorized as none; light (1-7 drinks per week); moderate (8-14 drinks per week); and heavy (15 or more drinks per week). One alcoholic beverage was equivalent to a 12-ounce beer, 5-ounce glass of wine or 1.5 ounces of hard liquor. The number of drinks per week were self-reported by each participant via a questionnaire when they enrolled in the study.

Blood pressure was categorized according to the 2017 American College of Cardiology/American Heart Association Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults as normal (below 120/80 mm Hg); elevated (120-129/

Researchers found:

light drinking was not associated with elevated blood pressure or either stage of high blood pressure;

moderate drinking was associated with increased odds of elevated blood pressure by 79%; Stage 1 high blood pressure by 66%; and Stage 2 high blood pressure by 62%;

heavy drinking was associated with increased odds of elevated blood pressure by 91%; Stage 1 high blood pressure by 149% (a 2.49-fold increase); and Stage 2 high blood pressure by 204% (a 3.04-fold increase); and

the more alcohol consumed, the higher the risk and severity of high blood pressure.

"Though light to moderate alcohol consumption may have positive effects on cardiovascular health in the general adult population, both moderate and heavy alcohol consumption appear to be independently associated with higher odds of high blood pressure among those with Type 2 diabetes," Singleton said. "Lifestyle modification, including tempering alcohol consumption, may be considered in patients with Type 2 diabetes, particularly if they are having trouble controlling their blood pressure.

"People with Type 2 diabetes are at higher cardiovascular risk, and our findings indicate that alcohol consumption is associated with hypertension, so limited drinking is recommended," Singleton said.

The study has several limitations including the fact that alcohol consumption was based on a one-time questionnaire when participants enrolled in the study, therefore the results do not account for any changes in alcohol consumption over time. In addition, the study was not designed to assess if light alcohol consumption provided any benefits.

According to the American Heart Association, excessive drinking can increase the risk of high blood pressure, and people with Type 2 diabetes are already at increased risk for high blood pressure. For the general population, the association recommends alcoholic beverages be consumed in moderation, if at all, and drinkers should understand the potential effects on their health.

Durham, NC - Results of a clinical trial released today in STEM CELLS Translational Medicine indicate that a combination of stem cell therapy and educational intervention can significantly help children with autism spectrum disorder (ASD).

"Social communication, language, and daily skills improved markedly within 18 months after stem cell transplantation. Conversely, repetitive behaviors and hyperactivity decreased remarkably," reported the study's corresponding author, Nguyen Thanh Liem, M.D., Ph.D. Dr. Liem, director of Vinmec Research Institute of Stem Cell and Gene Technology in Hanoi, is internationally recognized for his work in applying stem cells for different neurologic conditions (including cerebral palsy due to asphyxia, cerebral palsy related to neonatal icterus, cerebral palsy due to intracranial hemorrhage in neonatal period). He and his Vinmec team collaborated with researchers at Stanford University and Keele University on the two-year study.

ASD affects more than 18 out of every 1,000 children over the age of 8, according to the U.S.-based Centers for Disease Control. It involves a complex spectrum of disorders characterized by a deficit of social communication and interaction, restricted interest and repetitive verbal and nonverbal behavior. Children with ASD also commonly experience sleep disorders, seizures and gastrointestinal difficulties. While its cause has yet to be determined, many factors -- including genetic mutations, immune dysregulation, decreased blood flow in the brain, exposure to maternal antibodies during pregnancy and weak functional connectivity across brain regions -- appear to contribute to ASD's development. Multiple approaches including behavioral therapy, occupational therapy, speech therapy and medications are required to ameliorate its symptoms.

Educational and behavioral interventions are also crucial. The evidence indicates that young children with ASD benefit from interventions that focus on improving social interaction, communication and challenging behaviors. Unfortunately, however, many children who receive those treatments remain significantly impaired. "In search of better outcomes in the management of ASD, alternative and complementary treatments are being investigated," Dr. Liem said. "As stem cell therapy has shown promise in clinical trials treating several different types of neurological conditions such as cerebral palsy, cerebral trauma, spinal cord injury, researchers have theorized that it might be useful in treating ASD, too."

In fact, one recent study using a mouse strain bred to have autistic-like symptoms showed that transplantation of mesenchymal stem cells resulted in a reduction in stereotypical behaviors, a decrease in cognitive rigidity and an improvement in social behavior. This and other animal studies that proved the safety of the therapy paved the way for subsequent trials in children.

"However," Dr. Liem said, "while broadly consistent in outcome reporting, disparities remain around cell sources, processing, dosage and delivery route. The aim of our own study, then, was to investigate the safety and clinical outcomes of high-dosage autologous bone marrow mononuclear cell (BMMNC) transplantation combined with educational intervention."

Thirty children ranging in age from 3 to 7, with a confirmed autism diagnosis and whose CARS scores (which rates the level of ASD) placed them in the "severe" category, were selected for the open-labeled, uncontrolled trial. Each received an infusion of their own stem cells via injection into the space between their fourth and fifth lumbar vertebrae; six months later, the procedure was repeated.

After the first transplantation, all patients underwent eight weeks of educational intervention based on the Early Start Denver Model, a widely adopted play-based program that fuses behavioral and developmental principles. The children were then evaluated at intervals of six, 12 and 18 months, comparing their CARS and VABS (which measures adaptive behavior) scores with those at baseline. During this period there were no signs of any major adverse side effects.

"Although all participants still belonged to the severe level at the baseline after receiving behavioral intervention with a mean duration of 3.5 years, this study showed improvements in various aspects after BMMNC transplantation combined with educational intervention," Dr. Liem said. "Positive changes in social communication, eye contact, language, behaviors and daily skills were observed and learning ability also remarkably improved, especially after 18 months. Also, the rate of children with hyperactive disorder decreased by 50 percent and the number of children who can go to school without support increased."

Positive changes also were found in evaluation measures, including severity and adaptive ability. The number of patients requiring very substantial support decreased from 28 to 18.

"We noticed that the improvements appeared to be influenced by the CARS scores at baseline," Dr. Liem said. "Patients with a CARS score ? 49 at baseline showed better improvement than those who had CARS scores > 49 points. This would imply that patients with lesser severity had better outcomes after transplantation. We also noticed that the longer the follow-up duration was, the lower the severity of ASD and the better the children's adaptive functioning."

Meanwhile, the improvement increased progressively according to the follow-up duration, implying that the treatments have a sustainable long-term effect.

"Our study demonstrates the importance of balancing basic research and scientific rigor with compassionate use in translational medicine," the study authors emphasized. "While the mode-of-action of stem cell therapy is not yet completely understood, the positive results of this trial are testament to the safety and feasibility of applying stem cells toward treating diseases that have otherwise no, or only palliative, treatment options.

"Based on a sound scientific rationale and responsible clinical conduct, we believe that more extensive, controlled clinical trials will reveal the full potential of stem cell therapy for autism spectrum disorder."

"The clinical finding showing that the cell therapy treatment safely reduced severe autism spectrum disorder characterizations in children is encouraging," said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. "The findings are promising and open the opportunity for the development of a translational medicine approach that could help affected children."

The Sheffield researchers founded the spin-out Modulus Oncology with a team of experienced biotech entrepreneurs to fast-track the drug into clinical testing within two years.

A new drug which could improve life expectancy and quality for patients with hard-to-treat cancers, such as pancreatic cancer and relapsed breast cancer, has been invented by scientists at the University of Sheffield.

The researchers founded the spin-out company Modulus Oncology, along with a team of experienced biotech entrepreneurs, to fast-track the drug into clinical testing within two years.

The Sheffield team made the discovery after examining a hormone, called adrenomedullin, which controls blood pressure and other vital body processes, but also stimulates the growth and spread of cancer.

Using novel drug molecules, known as adrenomedullin-2 receptor antagonists, the scientists discovered a way to block the way that adrenomedullin is used in communication with cancer cells, without affecting the way it helps to regulate vital processes in the body such as blood pressure.

Findings of the pioneering study, published in the journal ACS Pharmacology & Translational Science, show the new drug molecules have a positive effect in the treatment of pancreatic cancer in mouse models.

Pancreatic cancer has the lowest survival rate of all common cancers, with only seven per cent of patients surviving five-years after diagnosis.

Professor Tim Skerry from the University of Sheffield's Department of Oncology and Metabolism and a team of academic and industrial scientists from a range of scientific disciplines have been working on the groundbreaking research for the past 12 years.

"The most extraordinary part of this new therapy is the fact that nature designed the hormone adrenomedullin to have two different types of receptor - one which helps to regulate our blood pressure and the other which is involved in the way that cancer cells communicate with each other and the host cells, helping cancers to grow and spread," said Professor Skerry.

"We have designed a unique piece to fit into nature's jigsaw which will block signals from one receptor but allow the other to work as normal. In blocking the hormone's communication with the cancer cells we are cutting off its supply to the things that it needs to thrive. This means tumours can't grow as fast as they are starved of the resources they need and it becomes more difficult for them to spread to other areas of the body.

He added: "Pancreatic cancer tumours are notoriously aggressive and difficult to treat and their location makes it easy for the cancer to spread to nearby organs such as the liver and stomach. The nature of pancreatic cancers means it is hard to get current drugs into the tumour. We believe adrenomedullin-2 receptors offer advantages for pancreatic cancer patients.

"Over the past 30 years the diagnosis and treatment of the vast majority of cancers has evolved rapidly, helping more people survive the disease than ever before. However, advances in treating pancreatic cancer and improving patient outcomes have had little effect on life expectancy. There are still cancers that are resistant to treatment and research is needed to solve those problems."

The novel drug molecules were found to be effective in treating pancreatic cancer tumours in mice models. Tumours did not grow as fast which provides evidence to suggest life expectancy would be extended. The compound is different from traditional therapies such as cytotoxic drugs and radiotherapy because it targets a very small number of cells and does not damage healthy cells in the body. It is hoped this will improve quality of life for patients undergoing treatment.

It is thought the concept will also be beneficial in other traditional hard-to-treat cancers such as relapsed breast cancer and lung cancer.

Building on more than a decade of research, and with substantial grant funding from The Wellcome Trust, the scientists created the spin-out company Modulus Oncology along with a team of biotech entrepreneurs.

Key members of the Modulus Oncology team include Professor Skerry and four of the company's co-founders: Dr Alan Wise, Chief Executive Officer; Dr Clare Wareing, Chief Business Officer; Dr Gareth Richards, a key discovery scientist on the programme who will assume the role of VP of Preclinical Biology; and Professor Joe Harrity, also a key member of the discovery team who will assume a role on the Scientific Advisory Board.

Dr Alan Wise, CEO of Modulus Oncology, said: "The team at the University of Sheffield have performed some truly pioneering research here and I am delighted to be helping Modulus Oncology take this vital work towards clinical testing. Our goal is to demonstrate benefit for cancer patients as well as growing a successful UK biotech company."

Modulus Oncology is currently in discussions with a number of life science investors to raise funding for first-in-human clinical trials designed to generate strong clinical proof of concept data.

For more information about Modulus Oncology, please contact: Dr Clare Wareing, CBO, cwareing@modulusoncology.com

Blocking an enzyme linked with inflammation makes it possible for stem cells to repair damaged heart tissue, new research from UC Davis Health scientists shows.

The enzyme -- soluble epoxide hydrolase, or sEH -- is a known factor in lung and joint disease. Now, it is a focus of heart-disease researchers as well.

The authors expect their work will lead to a new and powerful class of compounds that overcome the cell death and muscle thickening associated with heart failure -- a common outcome of a heart attack or long-term cardiovascular disease.

The study, conducted in mice, is published in Stem Cells Translational Medicine. The work was led by cardiologist Nipavan Chiamvimonvat.

"The science of using stem cell treatments for heart disease has been full of promise but little progress," Chiamvimonvat said. "The inflammation that accompanies heart disease is simply not conducive to stem cell survival."

Prior studies show that stem cells transplanted to the heart experience significant attrition in a very short period of time.

"We think we've found a way to quiet that inflammatory environment, giving stem cells a chance to survive and do the healing work we know they can do," said lead author and cardiovascular medicine researcher Padmini Sirish.

A significant and growing cardiovascular disease

Heart failure occurs when the heart no longer pumps blood efficiently, reducing oxygen throughout the body. Survival is around 45-60% five years after diagnosis. It affects approximately 5.7 million people in the U.S., with annual costs of nearly $30 billion. By 2030, it could affect as many as 9 million people at a cost of nearly $80 billion.

Chiamvimonvat often treats patients with heart failure and has been frustrated by the lack of effective medications for the disease, especially when it progresses to later stages. The best current therapies for end-stage heart failure are surgical -- heart transplants or mechanical heart pumps.

She expects her outcome will lead to a two-part treatment for end-stage heart failure that combines an sEH-blocking compound with stem cell transplantation.

Testing a two-step stem cell treatment

Chiamvimonvat and her team tested that theory in mice using cardiac muscle cells known as cardiomyocytes, which were derived from human-induced pluripotent stem cells (hiPSCs). A hiPSC is a cell taken from any human tissue (usually skin or blood) and genetically modified to behave like an embryonic stem cell. They have the ability to form all cell types.

The specific sEH inhibitor used in the study -- TPPU -- was selected based on the work of co-author and cancer researcher Bruce Hammock, whose lab has provided detailed studies of nearly a dozen of the enzyme inhibitors.

The researchers studied six groups of mice with induced heart attacks. A group treated with a combination of the inhibitor and hiPSCs had the best outcomes in terms of increased engraftment and survival of transplanted stem cells. That group also had less heart muscle thickening and improved cardiac function.

"Taken together, our data suggests that conditioning hiPSC cardiomyocytes with sEH inhibitors may help the cells to better survive the harsh conditions in the muscle damaged by a heart attack," Hammock said.

The path to clinical trials begins

Chiamvimonvat and her team will next test the process in a larger research animal model to provide more insights into the beneficial role of TPPU. She also wants to test the process with additional heart diseases, including atrial fibrillation. Her ultimate goal, in collaboration with Hammock, is to launch human clinical trials to test the safety of the treatment.

"It is my dream as a clinician and scientist to take the problems I see in the clinic to the lab for solutions that benefit our patients," Chiamvimonvat said. "It is only possible because of the incredible strength of our team and the extraordinarily collaborative nature of research at UC Davis."