Culture

Online diabetes prevention programs as effective as in-person programs for weight loss

FINDINGS

Researchers examined participation and weight loss results in an online diabetes prevention program; an in-person diabetes prevention program; and the Veterans Administration's face-to-face standard-of-care weight management program, called MOVE!

In the primary analysis, enrollees in the online diabetes prevention program saw a mean weight loss of 10.3 pounds at 6 months and 8.8 pounds at 12 months. In a secondary analysis of participants who completed one or more modules/sessions, mean weight loss for online participants was 10.6 pounds at six months and 9 pounds at one year. This was roughly comparable to the results of in-person participants, but significantly higher than it was for MOVE! participants in at least one meeting, who lost 1.1 pounds at six months and 10.6 pounds at one year. In addition, the researchers found that the online program had better participation than the in-person program, with 87 percent of online participants completing eight or more sessions, compared with 59 percent for the in-person program and 55 percent for MOVE!

This study is one of the first to assess weight outcomes in an online diabetes prevention program in comparison to in-person delivery of such a program.

BACKGROUND

Some 84 million, or one in three, U.S. adults have prediabetes, a condition in which one's blood sugar levels are consistently higher than normal, though not high enough to be type 2 diabetes. Without any intervention, up to 30 percent of adults with prediabetes can develop type 2 diabetes within five years, and up to 70 percent can develop it over their lifetime. Yet type 2 diabetes risk can be lowered by as much as 58 percent with lifestyle interventions such as diabetes prevention programs.

METHOD

The trial enrolled 268 obese or overweight veterans with prediabetes in an online program. In a separate trial, 273 were enrolled in an in-person program, and 114 were enrolled in MOVE! This study included only veterans, but participants were recruited from four large centers and were diverse. Participants were not randomly placed in a group and recruitment processes differed between the online and in-person programs.

The online program, developed by Omada Health, consisted of virtual groups of participants; live e-coaches who monitored group interactions and provided the participants with feedback via phone and private online messages; weekly educational modules on healthy eating and exercise; and wireless scales to record participant weights. The in-person program consisted of eight to 22 group-based face-to-face sessions focused on 7 percent weight loss and at least 150 minutes per session of moderate physical activity. The MOVE! program included eight to 12 face-to-face healthy-lifestyle sessions and monthly maintenance sessions, but with no specified goals. Weight change was measured at six months and again at 12 months.

IMPACT

An intensive, multifaceted online diabetes prevention program is as effective as in-person programs and can make prevention programs more accessible to those at risk for developing diabetes.

AUTHORS

First author was Dr. Tannaz Moin, assistant professor of medicine at the David Geffen School of Medicine at UCLA and core investigator at Veterans Affairs' Health Services Research & Development Center for the Study of Healthcare Innovation, Implementation and Policy. Other researchers were from the Veterans Administration, Duke University, Medical College of Wisconsin, University of Maryland, University of Minnesota and University of Michigan.

JOURNAL

The American Journal of Preventive Medicine published this study.

Credit: 
University of California - Los Angeles Health Sciences

Cryo-EM reveals structure of protein responsible for regulating body temperature

image: This is a cryo-EM image of TRPM2.

Image: 
Wei Lü and Juan Du

GRAND RAPIDS, Mich. (September 24, 2018) -- A team led by Van Andel Research Institute (VARI) scientists has revealed for the first time the atomic-level structure of TRPM2, a protein that may be a promising drug target for conditions such as Alzheimer's disease and bipolar disorder.

TRPM2 is found throughout the body and is integrally involved in regulating core body temperature, mediating immune responses and governing apoptosis, the programmed death of cells. It is activated by range of stimuli including oxidative stress, which results from chemical imbalances and is linked to numerous neurological conditions.

"TRPM2 is absolutely critical for healthy function but, until today, we were missing key insights into its structure and mechanism of action," said Juan Du, Ph.D., an assistant professor at VARI and co-senior author on a study describing TRPM2's structure, published today in Nature "It is our hope that these findings will act as a schematic for designing better and desperately needed medications for a host of neurological conditions."

The atomic-level images of TRPM2 depict a bell-like structure, with a transmembrane domain region on the bell's shoulder and an expanded NUDT9-H domain on the bell's lip. They also reveal a novel drug binding site for ADPR, a messenger molecule associated with oxidative stress and metabolism, which overturns the prevailing view that TRPM2 binds ADPR at the NUDT9-H domain. These revelations provide valuable details that could inform the design of therapeutic drugs to treat temperature-related diseases and prevent neuronal death in neurodegenerative diseases.

"Although we have known for some time that TRPM2 is a vital component of many biological processes and a possible drug target, we didn't know exactly what it looked like or how it worked," said Wei Lü, Ph.D., an assistant professor at VARI and co-senior author. "Today's findings change that, and go a long way toward a more comprehensive understanding of these incredibly important molecules."

TRPM2 belongs to the TRP superfamily, a group of proteins that mediate responses to sensory stimuli, such as pain, pressure, vision, temperature and taste. Broadly known as ion channels, proteins like TRP nestle within cells' membranes, acting as gatekeepers for chemical signals passing into and out of the cell. The eight proteins that comprise the TRPM subfamily are part of this broader group.

To date, TRPM2 is the fourth TRPM protein to have its structure resolved at the atomic level and the second TRPM protein to be determined at atomic resolution at VARI. In December, Lü and Du revealed the structure of TRPM4, which plays a role in regulating blood supply to the brain. It was the first structure of a TRPM protein determined at atomic resolution.

The findings were made possible by VARI's state-of-the-art David Van Andel Advanced Cryo-Electron Microscopy Suite, which allows scientists to view some of life's smallest components in exquisite detail. VARI's largest microscope, the Titan Krios, is so powerful that it can visualize molecules 1/10,000th the width of a human hair.

Credit: 
Van Andel Research Institute

Leading addiction experts call for more neuroscience research on long-term recovery

September is addiction recovery month, and, in the midst of the current opioid epidemic, it's an apt moment for addiction research experts to map the future path forward for a long-term recovery strategy for substance abuse. Warren Bickel, the director of the Virginia Tech Carilion Research Institute (VTCRI) Addiction Recovery Research Center, and Keith Humphreys, the Esther Ting Memorial Professor in psychiatry and behavioral science at Stanford University, called their colleagues to action in an article published in JAMA Psychiatry, a journal of the American Medical Association.

"More than 25 million people in the United States smoke cigarettes, and more than 20 million people meet diagnostic criteria for other substance use disorders," said Bickel, who also co-directs the VTCRI Center for Transformative Research on Health Behaviors. "That said, there are also more than 25 million Americans who have been in recovery for years, for decades. There's hope here."

Bickel pointed to the International Quit & Recovery Registry (IQRR) as an important research tool to advance understanding of long-term addiction recovery. Utilization of this tool could lead to better treatments for individuals who are not yet able to maintain long-term recovery, according to Bickel.

The IQRR, sponsored by VTCRI, has nearly 8,000 registrants from all 50 states, 40 countries, and five continents. Registrants' recovery times, from a variety of addictions, range from less than a year up to more than 20 years. Eighty-three percent of the participants identified two or more substances as their addictions of choice.

"This is the only registry of its type in the world, to my knowledge," Bickel said. To respect privacy, registrants do not have to submit their names. They are asked to provide a valid email address, zip code, and information about their addiction. "We're learning about the circumstances leading to addiction, the choices leading to recovery, and the social and cultural environments for people working through addiction."

Researchers have learned that addiction physically changes the brain, Bickel said, and ongoing research in the field has started to probe how even the briefest abstinence can change the brain further. The contributions from these studies are significant, according to Bickel and Humphreys, but they're not enough.

"There's a clear need for advancement in our knowledge of recovery processes. We need more information - basic information - about how the brain functions and heals during recovery," Bickel said. "Increasing the number of neuroscience studies and including longitudinal designs to understand how a person's brain changes after a few years or a few decades in recovery could have substantial clinical, scholarly, and public policy benefits."
Bickel and Humphreys plan to further address the questions they raised in their article, in anticipation of fostering more neuroscience research focused on long-term recovery from addiction.

"Understanding long-term recovery is important for science and for society," Humphreys said. "For science, unraveling the nature and treatment for medical disorders requires us to understand both the cause of disease, the course it takes, and the recovery--but in the addiction field, we have focused almost entirely on the first two. For society, while many people understandable despair over the horrors of the opioid epidemic, the reality of recovery gives us hope that happy and healthy lives are possible for those currently suffering."

Credit: 
Virginia Tech

Children whose mothers use marijuana try it at a younger age

Boston, MA - Children whose mothers use marijuana are more likely to start their own marijuana use an average of two years earlier than children whose mothers don't use the drug, according to a new study from Harvard T.H. Chan School of Public Health.

The study will be published September 24, 2018 in the American Journal of Preventive Medicine.

"Beginning marijuana use at a young age has been linked with negative cognitive and behavioral consequences," said Natasha Sokol, who led the study while a doctoral student at Harvard Chan School and is now a postdoctoral research fellow at Brown University School of Public Health's Center for Alcohol and Addiction Studies. "In a shifting regulatory environment in the U.S. in which the visibility and acceptability of adult marijuana use is expected to increase, it's important to better understand how these changes may impact children's early marijuana use so that we can better identify at-risk youth and implement effective prevention strategies."

Prohibiting marijuana isn't necessarily consistent with public health goals, according to the study authors. For example, marijuana has recognized therapeutic benefits for a number of health conditions, and may serve as a safer alternative to opioids. In addition, more than half of all drug arrests in the U.S. are marijuana-related and are a major driver of racial disparities in arrest and incarceration.

But in children who begin use at a young age, marijuana has been linked with negative consequences such as impairments in concentration and decision-making, increased impulsivity, and reductions in IQ. The younger a child is when he or she begins using marijuana, the more severe the effects, studies have suggested. Therefore, delaying marijuana initiation may be an important public health goal, the authors said.

Using data from the National Longitudinal Survey of Youth 1979 and Child and Young Adults, the new study assessed the timing and extent of marijuana use and initiation among 4,440 children and 2,586 mothers. Researchers tested for the effect of a mother's marijuana use between a child's birth and age 12 on that child's subsequent risk of marijuana initiation, controlling for factors related to the child's early life behavior and cognition and on the family's socioeconomic position and social environment.

The study found that 2,983 children (67.2%) and 1,053 mothers (35.3%) self-identified as marijuana users. Children whose mothers used marijuana were at increased risk for starting marijuana use prior to age 17, and they began using at a median age of 16, compared with age 18 for children whose mothers didn't use the drug. The association was slightly stronger among non-Hispanic non-black children.

One limitation of the study was that it did not measure whether children were aware of their mothers' marijuana use. The study also lacked data on the frequency and severity of mothers' marijuana use.

"Although more research is needed, physicians who prescribe marijuana might consider educating parents who use the drug about the potential dangers of early marijuana use among their children, and provide information and preventive strategies to delay such use," said Vaughan Rees, lecturer on social and behavioral sciences and director of Harvard Chan School's Center for Global Tobacco Control.

Credit: 
Harvard T.H. Chan School of Public Health

Children whose mothers use marijuana are more likely to try it at younger age

Ann Arbor, September 24, 2018 - When mothers use marijuana during the first 12 years of their child's life, their cannabis-using children are more likely to start at an earlier age than children of non-using mothers, according to a new study from the Harvard T.H. Chan School of Public Health published in the American Journal of Preventive Medicine. This study is the first to establish a relationship between maternal cannabis use during a child's lifetime and earlier initiation in a nationally-representative, longitudinal cohort, and examine the role of race, gender, and other social environmental factors.

"Early initiation is one of the strongest predictors of the likelihood of experiencing health consequences from marijuana use. In a shifting regulatory environment in which we expect adult marijuana use to become more normative, developing a deeper and more nuanced understanding of social risk factors for early initiation is a critical step in intervention design and delivery. Incorporating maternal cannabis use into our understanding of the important risk factors for early initiation may help us better identify at-risk youth for more tailored or intensive prevention strategies," explained lead investigator Natasha A. Sokol, ScD, currently of the Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University School of Public Health, Providence, RI, USA.

The investigators analyzed two linked cohorts of The National Longitudinal Survey of Youth 1979 (1980-1998 waves) and Child and Young Adults (1988-2014 waves) to assess the timing and extent of maternal and child marijuana use and initiation. They evaluated the data for 4,440 children and 2,586 mothers for the effect of maternal marijuana use between a child's birth and age 12 on that child's subsequent marijuana initiation, controlling for potentially important factors related to the child's early life behavior and cognition and the family's socioeconomic position and social environment. Overall, 2,983 children (67.2 percent) and 1,053 mothers (35.3 percent) self-identified as cannabis users. The investigators found that the children whose mothers used marijuana were at increased risk for marijuana initiation prior to age 17 and began at a median age of 16, compared to age 18 among children of non-users, noting that this effect was slightly stronger among non-Hispanic non-black children.

Although marijuana is generally thought to be less harmful compared with other drugs of abuse, the likelihood of experiencing health consequences associated with marijuana use is strongly linked to age at initiation, such that those who initiate earlier are at much greater risk. Negative consequences may be particularly marked for children and adolescents during these developmentally critical ages. Child and adolescent cannabis use is associated with impairments in attention, concentration, decision-making and working memory, and increased impulsivity, which may persist for weeks after use, with evidence that some cognitive effects, including reductions in IQ, may linger into adulthood. Among cannabis users, earlier initiation is associated with increased risk of anxiety and depressive disorders.

The United States is currently experiencing a sea change surrounding marijuana. This cultural shift is expected to result in increases in the prevalence, frequency, visibility, and/or acceptability of adult marijuana use. Understanding the impact of parent use on early marijuana initiation is an important step in anticipating the ways in which social environmental changes may alter the disease burden associated with marijuana in the US.

The findings indicate that children of marijuana-using parents may be an important subgroup for identification and early, evidence-based intervention by pediatricians and adolescent healthcare providers. Although future research on the mechanisms underpinning this relationship is necessary before more specific recommendations can be made, marijuana prescribers and other physicians may consider educating marijuana-using parents about early marijuana initiation and equipping them with evidence-based preventive strategies to delay marijuana use in their children. Further research may seek to understand best practices for preventing early initiation, such as decreasing or pausing use, reducing the visibility of use until children are older, and providing training, tools, and resources to help address these issues.

"Cannabis has recognized therapeutic benefits for treating a number of different medical conditions. There is also evidence that the availability of legal medical and recreational cannabis may reduce population opioid overdose deaths. Cannabis arrests account for more than half of all drug arrests in the US, and cannabis possession is a major driver of racial disparities in arrest and incarceration. For these reasons, total cannabis prohibition may not be consistent with public health objectives. Instead, given the neurocognitive, health, and social consequences associated with early use, delaying initiation may be an important, but undervalued, public health goal," commented Dr. Sokol.

Credit: 
Elsevier

Protein produced in gut could stave off deadly bone marrow transplant complication

(New York, NY - September 24, 2018) -- Researchers at Mount Sinai have discovered that an antimicrobial protein found in the gut can stave off a common and highly lethal side effect of bone marrow transplants, according to a study published in the Journal of Clinical Investigation in September.

The protein, regenerating islet-derived 3-alpha (REG3α), is made by cells in the lining of the gastrointestinal tract. It plays a role in a complication of bone marrow transplants called graft-versus-host-disease (GVHD), in which the donated bone marrow's immune cells attack the patient's gastrointestinal tract.

This study shows that GVHD causes increased serum levels of REG3α throughout the body while, paradoxically, decreasing the production of the protein in the gastrointestinal tract as GVHD worsens.

The Mount Sinai researchers showed that mice that could not make the protein did not survive GVHD, but also found that adding REG3α to human gastrointestinal cell lines prolonged their survival, confirming its unexpected function. These findings demonstrated that REG3α, previously only considered a biomarker for GVHD, can have a role in saving patients from the disease.

While patients suffering from GVHD are normally given immune suppressants, this research suggested that enhancing the immune system with REG3α is a better strategy and may also be helpful for illnesses such as inflammatory bowel disease that also involve the immune system in the gastrointestinal tract.

"There is a way to treat immune disorders of the gastrointestinal tract by enhancing the immune system rather than suppressing it, as we do now," said lead researcher James Ferrara, MD, Ward-Coleman Chair of Cancer Medicine and Director of the Hematologic Malignancies Translational Research Center at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai and Co-Director of the Mount Sinai Acute GVHD International Consortium (MAGIC). "These results show a new function for the lining of the gastrointestinal tract protecting itself, leading to a new class of drugs."

Credit: 
The Mount Sinai Hospital / Mount Sinai School of Medicine

LGBT community has poorer mental health

image: Pictured L to R: Third-year MCG student Lauren Wooten Smith, MCG psychologist Dr. Lara Stepleman, Assistant Professor of Psychiatry and Health Behavior Dr. Devon Eldridge and fourth-year MCG student Jiby Yohannan

Image: 
Phil Jones, Senior Photographer, Augusta University

AUGUSTA, Ga. (Sept. 24, 2018) - The local LGBT community reports twice the number of poor mental health days as the general population of Richmond and Columbia Counties, and those who identified as transgender report twice that, according to a health needs assessment conducted by faculty and students at the Medical College of Georgia at Augusta University.

Area LGBT individuals reported an average of 7.8 poor mental health days, defined as any day they struggled with mental health issues like stress, depression, anxiety and other emotional problems. Those who identified as transgender reported even more days - individuals born female who currently identify as male reported 15.4 days and individuals born male who currently identify as female reported 12.4 days.

The average numbers of poor mental health days on previous assessments of Richmond and Columbia Counties were 3.4 and 2.8, respectively.

"The mental health metrics we measured were the most astonishing in how they differed from the population in general for this area," says Dr. Lara Stepleman, a psychologist in MCG's Department of Psychiatry and Health Behavior.

Around 30 percent of the LGBT sample also reported having suicidal thoughts during their lifetime and 18.5 had actually attempted suicide. Of those who identified as transgender, almost half reported a history of suicidal thoughts and nearly 35 percent had actually attempted.

"In the national data, over and over you find the transgender community fairing far worse," Stepleman says. "There are a lot of reasons - the transgender population as a whole faces much more stigma and can have a harder time finding employment for instance. That type of discrimination leads to other problems like less access to insurance, and therefore access to things they need to gender transition, to live more fully."

The MCG assessment, which is providing the first look at the health needs of the local LGBT community, was taken by 436 people in Augusta and the surrounding area over a five-month period in 2016. The hope is that it will help health care providers better understand the impact of minority stress on other health variables, she says of the assessment results, which are published in the Journal of Homosexuality.

"LGBT people experience the same stressors that anyone else does and when you add their internalized feelings and perceptions of discrimination, there are obvious implications for overall health," Stepleman says. "This assessment is meant to provide an overview, but it helps establish an important baseline and will help us look at the impact of minority stress on a lot of other health variables."

Minority stress describes chronically high levels of stress faced by members of minority groups and can be due to things like poor social support and low socioeconomic status. Many studies have shown that it can contribute to health problems like high blood pressure and anxiety.

The physical health metrics the group measured were less stark, but still concerning, Stepleman says. Asked to number the days they had experienced poor physical health in the last month, the LGBT sample reported 4.5 days. People in Richmond and Columbia Counties previously reported 3.4 and 2.8, respectively.

Around 20 percent of LGBT individuals reported not having health insurance. On the surface, that is not that different from the rest of the community, Stepleman says. "But it is when you consider our sample was largely college-educated, middle-class people. And with the transgender community, even if they do have insurance, many plans still do not fully cover gender transition medications or surgeries."

Other concerns identified by the LGBT assessment included:

A third of the sample reported that they had no
identified or consistent primary care provider.

Almost 50 percent found that their providers needed
more training in LGBT health.

65 percent found community member stigma against
LGBT people a problem - at least a small problem or
higher.

Stepleman and third-year medical student Lauren Wooten Smith spearheaded the design of the survey, which asked 86 questions about various health concerns - both perceived overall wellness and actual disease states they experienced.

Credit: 
Medical College of Georgia at Augusta University

Sex in plants requires thrust

video: Turns out it takes a combination of prodding and a lot of communication and guidance

Image: 
McGill University

Plant sex relies on a combination of prodding and a lot of communication and guidance suggests a study published in the September 2018 issue of Technology.

It's a process that is fraught with challenges. The sperm, two of which are housed in each grain of pollen, are unable to move on their own and the egg cell is deeply embedded in the pistil (the female tissues of the flower). So, to reach the egg the sperm rely on a pollen tube that extends into the pistil. These invasive tubes are the fastest growing cells in the plant kingdom, growing up to 1-2 cm (or 500x their original dimension) an hour, and can sometimes extend up to 30 cm, depending on the anatomy of the flower. To fertilize the egg, the pollen tube (which is between 1/20 and 1/5 of the width of a human hair) has to navigate through a maze of tissue, no matter what obstacles it encounters. The phenomenon is well-documented and known to require communication at cellular level with the female flower tissues, but relatively little is understood about the cell mechanics involved. So scientists from McGill and Concordia collaborated to look more closely at the growth force of individual pollen tubes using a microfluidic lab-on-a-chip.

"From a mechanical point of view, the process of pollen tube elongation is similar to that of a balloon catheter used in angioplasty - forces are generated based on fluid under pressure," explains Muthukumaran Packirisamy from Concordia University's Department of Mechanical and Industrial Engineering. "So, we designed a microscopic cantilever with a gauge built-in that the pollen tubes had to forcefully push against in order to continue to elongate."

Anja Geitmann, formerly at l'Université de Montréal who is now Canada Research Chair in McGill's Department of Plant Science is the senior author on the paper. She adds:

"Thanks to the lab-on-a chip technology we were able to actually see and measure exactly what was going on within the pollen tube as it grew. We discovered that the water pressure and force that these tiny cells exert as they push through the plant tissue to reach their destination is equivalent to the air pressure we put in our car tires to keep them rolling. What is even more exciting is that we found that when the pollen tube encounters an obstacle, it changes its growth pattern, suggesting that the cells are in some ways able to 'feel' and respond to the physical resistance in their environment. It's very exciting to be able to see this process, and it leaves us with a lot of interesting questions ahead about male-female communication."

Credit: 
McGill University

In most countries, liberalism correlates to climate change acceptance - in the US, social authoritarianism does

Belief in free elections, freedom of religion, equal rights for women, freedom of speech, freedom of the press, lack of Internet censorship and are other democratic values are strong predictors for acceptance of climate change - but in the US it is being a Democrat, including tendencies toward social authoritarianism with bans, regulations, and shouting down of alternatives, where climate change acceptance is stronger than among those who believe in liberty and individual freedom.

New findings on the muscle disease Laing early-onset distal myopathy

image: This is Homa Tajsharghi, professor of biomedicine, University of Skövde.

Image: 
University of Skövde

New avenues are now being opened for future treatment of Laing distal myopathy, a rare disorder that causes muscles in the feet, hands and elsewhere to atrophy. In a study published in the journal PNAS, researchers have identified an enzyme with a clear link to how the disease develops.

"Now we know that the levels of enzyme activity are an important factor in how quickly the disease progresses. This may mean that the disease could be treated by artificially increasing the activity," says Martin Dahl Halvarsson, PhD student in pathology at the Institute of Biomedicine at Sahlgrenska Academy, and the study's first author.

The muscle disease Laing early-onset distal myopathy is caused by an inherited mutation in a muscle protein, myosin, that normally contributes to muscle contraction. The disease often appears at a young age, from age 5 up to about age 20.

What happens with Laing is that muscle fibers, primarily in the legs, hands, hips, neck and shoulders, atrophy over a period of time. With reduced strength and mobility, patients experience impaired quality of life in the long term. How much and how quickly the disease develops varies greatly, however.

In the current study led by Homa Tajsharghi, professor of biomedicine at the University of Skövde, researchers for the first time introduced the mutation for the disease in an entire organism. This was done through mutation of the gene for myosin in fruit flies. The team's previous research has been based on cell culture experiments and experiments outside living organisms.

In this study mutant flies were crossed with fruit flies that had acquired the property of overproducing a particular enzyme. This property is called Abba in fruit flies and MuRF in humans. This sends signals to the cell's proteasome system to destroy the damaged muscle protein.

The researchers then examined several aspects of both the larvae and the adult flies. They studied both how myosin and other proteins organize themselves over a period of time in diseased fruit flies. They also looked at the crawling patterns of the larvae and the adult flies' ability to jump and climb.

The results show that Laing early-onset distal myopathy manifests itself similarly in fruit flies and humans and that the Abba enzyme constitutes a counterbalance to the mutation. Fruit flies with an overproduction of Abba are immune to the disease, provided they are heterozygotes, with one mutated and one normal gene.

The homozygote flies, with double mutations, did not survive to adulthood. In humans, however, homozygotes have never been diagnosed. This might be because people cannot survive with double mutations.

"We have treated diseased fruit flies that carry the same genetic change as patients with Laing distal myopathy," says Homa Tajsharghi, corresponding author behind the study. "The flies were cured and recovered muscle strength and the ability to fly. Naturally there are differences between fruit flies and humans, and additional studies are needed."

Credit: 
University of Gothenburg

Spray-on antennas could unlock potential of smart, connected technology

image: Researchers from Drexel University's College of Engineering have developed a way to "spray paint" invisibly thin antennas from a type of two-dimensional material called MXene. The antennas perform as well or better than the ones currently used in mobile devices and RFID tags.

Image: 
Drexel University - Kanit Hantanasirisakul

The promise of wearables, functional fabrics, the Internet of Things, and their "next-generation" technological cohort seems tantalizingly within reach. But researchers in the field will tell you a prime reason for their delayed "arrival" is the problem of seamlessly integrating connection technology - namely, antennas - with shape-shifting and flexible "things."

But a breakthrough by researchers in Drexel's College of Engineering, could now make installing an antenna as easy as applying some bug spray.

In research recently published in Science Advances, the group reports on a method for spraying invisibly thin antennas, made from a type of two-dimensional, metallic material called MXene, that perform as well as those being used in mobile devices, wireless routers and portable transducers.

"This is a very exciting finding because there is a lot of potential for this type of technology," said Kapil Dandekar, PhD, a professor of Electrical and Computer Engineering in the College of Engineering, who directs the Drexel Wireless Systems Lab, and was a co-author of the research. "The ability to spray an antenna on a flexible substrate or make it optically transparent means that we could have a lot of new places to set up networks - there are new applications and new ways of collecting data that we can't even imagine at the moment."

The researchers, from the College's Department of Materials Science and Engineering, report that the MXene titanium carbide can be dissolved in water to create an ink or paint. The exceptional conductivity of the material enables it to transmit and direct radio waves, even when it's applied in a very thin coating.

"We found that even transparent antennas with thicknesses of tens of nanometers were able to communicate efficiently," said Asia Sarycheva, a doctoral candidate in the A.J. Drexel Nanomaterials Institute and Materials Science and Engineering Department. "By increasing the thickness up to 8 microns, the performance of MXene antenna achieved 98 percent of its predicted maximum value."

Preserving transmission quality in a form this thin is significant because it would allow antennas to easily be embedded - literally, sprayed on - in a wide variety of objects and surfaces without adding additional weight or circuitry or requiring a certain level of rigidity.

"This technology could enable the truly seamless integration of antennas with everyday objects which will be critical for the emerging Internet of Things," Dandekar said. "Researchers have done a lot of work with non-traditional materials trying to figure out where manufacturing technology meets system needs, but this technology could make it a lot easier to answer some of the difficult questions we've been working on for years."

Initial testing of the sprayed antennas suggest that they can perform with the same range of quality as current antennas, which are made from familiar metals, like gold, silver, copper and aluminum, but are much thicker than MXene antennas. Making antennas smaller and lighter has long been a goal of materials scientists and electrical engineers, so this discovery is a sizeable step forward both in terms of reducing their footprint as well as broadening their application.

"Current fabrication methods of metals cannot make antennas thin enough and applicable to any surface, in spite of decades of research and development to improve the performance of metal antennas," said Yury Gogotsi, PhD, Distinguished University and Bach professor of Materials Science and Engineering in the College of Engineering, and Director of the A.J. Drexel Nanomaterials Institute, who initiated and led the project. "We were looking for two-dimensional nanomaterials, which have sheet thickness about hundred thousand times thinner than a human hair; just a few atoms across, and can self-assemble into conductive films upon deposition on any surface. Therefore, we selected MXene, which is a two-dimensional titanium carbide material, that is stronger than metals and is metallically conductive, as a candidate for ultra-thin antennas."

Drexel researchers discovered the family of MXene materials in 2011 and have been gaining an understanding of their properties, and considering their possible applications, ever since. The layered two-dimensional material, which is made by wet chemical processing, has already shown potential in energy storage devices, electromagnetic shielding, water filtration, chemical sensing, structural reinforcement and gas separation.

Naturally MXene materials have drawn comparisons to promising two-dimensional materials like graphene, which won the Nobel Prize in 2010 and has been explored as a material for printable antennas. In the paper, the Drexel researchers put the spray-on antennas up against a variety of antennas made from these new materials, including graphene, silver ink and carbon nanotubes. The MXene antennas were 50 times better than graphene and 300 times better than silver ink antennas in terms of preserving the quality of radio wave transmission.

"The MXene antenna not only outperformed the macro and micro world of metal antennas, we went beyond the performance of available nanomaterial antennas, while keeping the antenna thickness very low," said Babak Anasori, PhD, a research assistant professor in A.J. Drexel Nanomaterials Institute. "The thinnest antenna was as thin as 62 nanometers - about thousand times thinner than a sheep of paper - and it was almost transparent. Unlike other nanomaterials fabrication methods, that requires additives, called binders, and extra steps of heating to sinter the nanoparticles together, we made antennas in a single step by airbrush spraying our water-based MXene ink."

The group initially tested the spray-on application of the antenna ink on a rough substrate - cellulose paper - and a smooth one - polyethylene terephthalate sheets - the next step for their work will be looking at the best ways to apply it to a wide variety of surfaces from glass to yarn and skin.

"Further research on using materials from the MXene family in wireless communication may enable fully transparent electronics and greatly improved wearable devices that will support the active lifestyles we are living," Anasori said.

Credit: 
Drexel University

It's not just for kids -- even adults appear to benefit from a regular bedtime

DURHAM, N.C. -- Sufficient sleep has been proven to help keep the body healthy and the mind sharp. But it's not just an issue of logging at least seven hours of Z's.

A new study on sleep patterns suggests that a regular bedtime and wake time are just as important for heart and metabolic health among older adults.

In a study of 1,978 older adults publishing Sept. 21 in the journal Scientific Reports, researchers at Duke Health and the Duke Clinical Research Institute found people with irregular sleep patterns weighed more, had higher blood sugar, higher blood pressure, and a higher projected risk of having a heart attack or stroke within 10 years than those who slept and woke at the same times every day.

Irregular sleepers were also more likely to report depression and stress than regular sleepers, both of which are tied to heart health.

African-Americans had the most irregular sleep patterns compared to participants who were white, Chinese-American or Hispanic, the data showed.

The findings show an association -- not a cause-and-effect relationship -- between sleep regularity and heart and metabolic health.

"From our study, we can't conclude that sleep irregularity results in health risks, or whether health conditions affect sleep," said Jessica Lunsford-Avery, Ph.D., an assistant professor in psychiatry and behavioral sciences and the study's lead author. "Perhaps all of these things are impacting each other."

Still, the data suggest tracking sleep regularity could help identify people at risk of disease, and where health disparities may impact specific groups, such as African Americans.

"Heart disease and diabetes are extremely common in the United States, are extremely costly and also are leading causes of death in this country," she said. "To the extent we can predict individuals at risk for these diseases, we may be able to prevent or delay their onset."

Participants used devices that tracked sleep schedules down to the minute so researchers could learn whether even subtle changes -- going to bed at 10:10 p.m. instead of the usual 10 p.m. -- were linked to the health of participants. Their ages ranged from 54 to 93, and people with diagnosed sleep disorders such as sleep apnea were not included.

The study also tracked the duration of participants' sleep and preferred timing -- whether someone turned in early or was a night owl. According to these measures, people with hypertension tended to sleep more hours, and people with obesity tended to stay up later.

Of all three measures, however, regularity was the best at predicting someone's heart and metabolic disease risk, the researchers found.

As one might expect, irregular sleepers experienced more sleepiness during the day and were less active -- perhaps because they were tired, Lunsford-Avery said.

Researchers plan to conduct more studies over longer periods in hopes of determining how biology causes changes in sleep regularity and vice-versa.

"Perhaps there's something about obesity that disrupts sleep regularity," Lunsford-Avery said. "Or, as some research suggests, perhaps poor sleep interferes with the body's metabolism which can lead to weight gain, and it's a vicious cycle. With more research, we hope to understand what's going on biologically, and perhaps then we could say what's coming first or which is the chicken and which is the egg."

Credit: 
Duke University Medical Center

Pre-clinical success for a universal flu vaccine offers hope for third generation approach

Researchers from the University of Oxford's Department of Zoology have demonstrated pre-clinical success for a universal flu vaccine in a new paper published in Nature Communications.

Influenza is thought to be a highly variable virus, able to mutate and escape immunity built up in the population due to its circulation in previous seasons. However, influenza seasons tend to be dominated by a limited number of antigenically and genetically distinct influenza viruses. This creates a paradox as influenza is thought of as being highly variable while in reality influenza seasons are dominated by only a few strains.

Mathematical models produced in Professor Sunetra Gupta's group at the University of Oxford over the past 20 years have sought to find an answer to this paradox. Finally, through a collaborative approach across multiple departments, the group believes they have the answer.

Dr Craig Thompson said: 'The integrated approach to vaccine design that we have applied to flu has to the potential to be applied to other previously intractable pathogens and could revolutionise the way we develop vaccines.'

Professor Sunetra Gupta said: 'I think this work serves a good example of how evolutionary models can have translational impact. We have gone from a prediction of a mathematical model to a blueprint for a universal influenza vaccine. The outstanding teamwork coordinated by Dr Thompson is what made it all possible.'

The research team theorized that parts of the virus targeted by the immune system are, in fact, limited in variability and act as constraints on the evolution of the virus. Dr Craig Thompson in Professor Gupta's group has now identified the location of these regions of limited variability. He has shown that such locations are targeted naturally by the immune system and through vaccination studies has shown that regions of influenza viruses that circulated in 2006 and 1977 were able to protect against infection with an influenza virus that last circulated in 1934.

Thirty mice were vaccinated with the epitopes identified in the study. Twelve mice were vaccinated with a control vaccine (a vaccine not containing the epitopes identified in the study but otherwise essentially the same as the vaccine containing the epitopes identified). Twelve mice were 'mock vaccinated' with no vaccine (just PBS/adjuvant without vaccine). Six mice were used as a normal control and were not vaccinated in any way.

The researchers identified regions of the virus which were limited in variability by mapping the historical variation of the influenza virus to the main target of the immune system - an influenza protein called 'haemagglutinin'. This allowed them to identify several regions of the protein which were previously thought of as highly variable as limited in variability. Further computational analysis showed that one of these regions cycled through a number of different states between 1918 and the present day. The researchers then showed that sera from children aged 6 to 12 cross-reacted to historical strains which they could not possibly have experienced. Mutagenesis of one of the regions identified in our bioinformatic/computational analysis from one state to another removed this cross reactivity. The research team then vaccinated mice with the individual versions of the region which induced periodic cross-reactivity to historical strain in mice - vaccination of mice with one of the versions reproduced exactly the cross reactivity produced by the sera from the children. They then showed that the versions of this region identified by our analysis and serology work that circulated in 1977 and 2006 were able to protect mice from a lethal challenge with an influenza virus that last circulated in 1934.

This experimental setup utilising a lot of controls allowed researchers to determine precisely that the epitopes they had identified were responsible for the cross-reactivity that researchers observed in the study.

The results of these studies can be exploited to create a novel type of 'universal' or broadly protective influenza vaccine, which once administered would provide lifelong protection against influenza. The team also hopes to apply the approach to other viruses such as HIV and HCV and believes that they can use it to produce a vaccine that protects against the common cold. The novel approach to vaccine design is outlined in the paper published in Nature Communications. Furthermore, such vaccines should be able to be produced in a low-cost manner, enabling healthcare providers such as the NHS to save money, unlike many new vaccines and drugs coming to the market.

This study also presents one of the first examples of where a mathematical model of the evolutionary dynamics of an infectious disease has led to the experimental identification of a novel vaccine target. The novel approach won an MRC Confidence in Concept Award in 2016, a Royal Society Translational Award in 2017 and an ERC Proof of Concept grant in 2018.

The WHO estimates that influenza kills 260,000-650,000 people and causes 3-5 million cases of severe illness each year. This burden typically falls on the elderly and young children, especially in developing countries. The best way to protect against influenza is through vaccination, although the problem with this is that the current influenza vaccine has to be administered each year and varies in its effectiveness.

Credit: 
University of Oxford

Latest research hints at predicting autism risk for pregnant mothers

image: Juergen Hahn, professor and head of biomedical engineering

Image: 
Rensselaer Polytechnic Institute

Researchers at Rensselaer Polytechnic Institute--led by Juergen Hahn, professor and head of biomedical engineering--are continuing to make remarkable progress with their research focused on autism spectrum disorder (ASD). A recent paper authored by Hahn and Jill James from the University of Arkansas for Medical Sciences (UAMS) in the journal Research in Autism Spectrum Disorders discusses their work on predicting with approximately 90 percent accuracy whether a pregnant mother has a 1.7 percent or a tenfold increased risk of having a child diagnosed with ASD.

Currently there is no test for pregnant mothers that can predict the probability of having a child that will be diagnosed with ASD. Recent estimates indicate that if a mother has previously had a child with ASD, the risk of having a second child with ASD is approximately 18.7 percent, whereas the risk of ASD in the general population is approximately 1.7 percent.

"However," said Hahn, a member of the Rensselaer Center for Biotechnology and Interdisciplinary Studies, "it would be highly desirable if a prediction based upon physiological measurements could be made to determine which risk group a prospective mother falls into."

Hahn's work in developing a physiological test to predict autism risk is part larger emphasis on Alzheimer's and neurodegenerative diseases at the Center for Biotechnology and Interdisciplinary Studies, and an example of how the interdisciplinary life science and engineering interface at Rensselaer offers new perspectives and solutions for improving human health.

In this study, metabolites of the folate-dependent transmethylation and transsulfuration biochemical pathways of pregnant mothers were measured to determine whether or not the risk of having a child with autism could be predicted by her metabolic profile. Pregnant mothers who have had a child with autism before were separated into two groups based on the diagnosis of their child whether the child had autism or not. Then these mothers were compared to a group of control mothers who have not had a child with autism before.

The researchers concluded that while it is not possible to determine during a pregnancy if a child will be diagnosed with ASD by age 3, they did find that differences in the plasma metabolites are indicative of the relative risk (18.7 percent vs 1.7 percent) for having a child with ASD.

"These are exciting results as they hint at differences in some metabolic processes that potentially play a role in increasing the risk of having a child with ASD," said Hahn.

In addition to the lead authors, Juergen Hahn of Rensselaer and Jill James of UAMS, this work included collaborators from Rensselaer, the University of Arkansas for Medical Sciences, and the MIND Institute at UC Davis.

This new research follows an earlier study published in 2017, which developed an algorithm based on levels of metabolites found in a blood sample that can accurately predict whether a child is on the autism spectrum. A follow-up study this spring was also highly promising in assessing whether a child is on the autism spectrum. These results have the potential for earlier diagnosis for ASD, and efforts are underway to develop a commercially available test based upon these findings.

Credit: 
Rensselaer Polytechnic Institute

A Trojan Horse delivery for treating a rare, potentially deadly, blood-clotting disorder

image: X. Long Zheng

Image: 
UAB

BIRMINGHAM, Ala. - In proof-of-concept experiments, University of Alabama at Birmingham researchers have highlighted a potential therapy for a rare but potentially deadly blood-clotting disorder, TTP. The researchers deliver this therapeutic enzyme via the cellular equivalent of a Trojan Horse, using tiny blood cell platelets as their protective delivery vehicle, with a key enzyme hidden inside.

TTP, or thrombotic thrombocytopenic purpura, appears as blood clots in small arterioles throughout the body, particularly in the brain, heart, pancreas and kidneys, resulting in organ damage. The onset of symptoms can be sudden and nonspecific, and the in-hospital death rate remains as high as 20 percent.

TTP is caused by lack of the enzyme ADAMTS13 in the blood, most often because of autoantibodies against this enzyme. ADAMTS13 normally acts to cleave a large protein called von Willebrand factor, which is involved in blood clotting. Loss of the enzyme allows destructive microvascular clots to form in important organ tissues.

UAB researchers, led by X. Long Zheng, M.D., Ph.D., Robert B. Adams Professor and Division Director of Laboratory Medicine in the Department of Pathology in UAB's School of Medicine, have now reported that platelets can spontaneously take up ADAMTS13. The enzyme stays stable in those cells, and the platelets can effectively deliver the enzyme where it is needed.

In ex vivo experiments with human blood from TTP patients and in vivo experiments with a mouse model of TTP, the researchers showed that human recombinant ADAMTS13, or rADAMTS13, carried in the platelets can "dramatically" reduce the rate and final amount of blood clot formation in injured arterioles.

"Our results for the first time demonstrate that transfusion of rADAMTS13-loaded platelets may be a novel and potentially effective therapeutic approach for arterial thrombosis, associated with congenital and immune-mediated TTP," Zheng said. "This novel approach could be translated to patient care once rADAMTS13 receives an approval from the U.S. Food and Drug Administration for therapy of congenital TTP."

In previous work published in Blood in 2015, the UAB researchers created transgenic mice, where human rADAMTS13 was expressed exclusively in the platelets. In a background of mice lacking their own ADAMTS13 enzyme, the rADAMTS13-loaded platelets blocked arterial thrombosis and prevented TTP in the mouse model.

As the next step toward patient care, Zheng and colleagues sought to determine whether platelets outside of the body could be loaded with rADAMTS13, such as in blood collected for transfusions. If so, they also wanted to test whether transfusion with those rADAMTS13-loaded platelets could be as effective to block thrombosis and prevent TTP in mice as the transgenic platelets that expressed high levels of rADAMTS13.

Four key experiments -- described in a study published in the American Heart Association journal Arteriosclerosis, Thrombosis and Vascular Biology, or ATVB -- answered those questions.

First, the researchers incubated isolated human platelets -- which are one-fifth the diameter of red blood cells and have a normal function to stop bleeding from blood vessels -- for up to two hours in varying concentrations of rADAMTS13 at varying temperatures. At the cold temperature of 4 C, the platelets did not take up rADAMTS13. But at both 25 and 37 C, the platelets took up rADAMTS13, apparently through endocytosis, in a concentration-dependent manner.

Second, they showed that the rADAMTS13 taken up by the human platelets remained intact and enzymatically active against von Willebrand factor, a key ingredient for platelet adhesion and aggregation. Also, the rADAMTS13 was releasable under arterial shear conditions that cause platelet aggregates to break, as simulated with microfluidic channels.

Third, using microfluidic channels coated with a fibrillar collagen that simulates the flow in arterioles and presents a surface for clot formation, they showed that addition of rADAMTS13-loaded platelets to normal, TTP-patient and reconstituted-TTP blood dramatically inhibited in vitro thrombus formation under arterial flow.

Finally, they showed that transfusion of the rADAMTS13-loaded mouse platelets into genetically engineered mice lacking ADAMTS13 dramatically inhibited thrombus formation in abdominal arterioles after injury.

Thus, it may be possible to pack rADAMTS13 inside human platelets during the time that bags of donated blood sit at room temperature for three days as they are tested for multiple infectious disease markers. These packed platelets could then be transfused into patients with TTP. While routine transfusion of platelets in TTP patients is not recommended, transfusion of rADAMTS13-loaded platelets clearly showed a therapeutic benefit by inhibiting thrombus formation in human and mouse blood lacking ADAMTS13 enzyme.

Other researchers have worked on therapeutic strategies to bypass the autoantibody for TTP treatment, with some success. However, unlike Zheng's platelet-ADAMTS13 approach, none of those strategies have addressed the underlying mechanism of TTP -- a lack of ADAMTS13 and/or autoantibody against ADAMTS13.

Credit: 
University of Alabama at Birmingham