Culture

IADR's Women Pioneers: Celebrating a Century of Achievement published in Advances in Dental Research

Alexandria, VA, USA - In 2019 the Journal of Dental Research (JDR) proudly celebrates its Centennial! The latest issue of Advances in Dental Research, an e-Supplement to the Journal of Dental Research (JDR), "IADR's Women Pioneers: Celebrating a Century of Achievement" highlights the history of the tremendous advancements in dental research made by women, while also identifying areas where the profession needs to continue to grow to be more inclusive in the promotion of women scientific innovators.

Many women have had an impact on dental, oral and craniofacial research throughout its evolution, yet it took 60 years before Marie Nylen was elected as the first women IADR President in 1981. Nylen and other trailblazing women who have shaped the IADR are highlighted in this issue, including the individual careers of the 11 IADR women presidents. Issues discussed range from unconscious and conscious biases that have prevented women from initial entry into dental schools over 100 years ago, to the more present-day challenges of breaking through the glass ceiling for leadership positions.

"The advances towards gender parity made as showcased by the IADR and our dental research community have been remarkable, but they are still inadequate," said IADR Immediate Past President and guest editor Rena D'Souza, University of Utah, Salt Lake City, USA. "Ways to continue advancing women in dental research include unconscious bias training for research academic team members, the better creation of allies of women and under-represented groups, continued data collection on the recruitment and retention of women in STEMM and cultivating institutions that value equity for women through the enforcement of equity guidelines at every level, including hiring and promotion."

"The IADR has done much to promote greater opportunity for women, with more women presenters at annual meetings, a 50% representation of IADR women presidents over the most recent 10 years and the development of innovative programs such as the IADR Women in Science Network," said guest editor Tamanna Tiwari, University of Colorado, Aurora, USA. "We hope the information in this issue will help to inspire the next generation women leaders in the dental, oral and craniofacial research community."

"This Advances in Dental Research issue is important because it discusses gender equity issues in dental, oral and craniofacial research as well as expands on institutional strategies towards parity," said guest editor Effie Ioannidou, University of Connecticut, Farmington, USA. "We feel this will be the beginning of a dialogue among stakeholders, which will enhance diversity and equity in the field."

"This is a wonderful collection showcasing the important contributions of women of the IADR and to dental research over the past century," said JDR Editor-in-Chief William Giannobile, University of Michigan, Ann Arbor, USA. "I am so pleased we could publish this special issue of the Advances of Dental Research as a part of our 100 year celebration."

Credit: 
International Association for Dental, Oral, and Craniofacial Research

The evolution of neuroscience as a research

Alexandria, VA, USA - 2019 marks the Centennial of the Journal of Dental Research (JDR). Over the last century the JDR has been dedicated to the dissemination of new knowledge and information on all sciences relevant to dentistry and to the oral cavity and associated structures in health and disease. To celebrate, the JDR is featuring a yearlong, commemorative article and podcast series that highlights topics that have transformed dental, oral and craniofacial research over the past 100 years.

When the first issue of the JDR was published, the field of neuroscience did not exist but over subsequent decades neuroscience has emerged as a scientific field that has particular relevance to dentistry. In the JDR Centennial article "The Evolution of Neuroscience as a Research Field Relevant to Dentistry," Koichi Iwata, Nihon University, Tokyo, Japan and Barry Sessle, University of Toronto, Ontario, Canada review many of the novel insights that have been gained through neuroscience research into the neural basis of these functions and their clinical relevance to the diagnosis and management of pain and sensorimotor disorders.

"Neuroscience is relevant to dentistry as many neurally-based functions, such as pain, taste, chewing, swallowing and salivation, are manifested in the orofacial area and disorders of these functions are quite common," said Iwata. He also noted that "neuroscience research has resulted in greater understanding of these functions. Novel insights have been gained of the neural pathways and brain circuitry underlying each of these functions and also of the role of nonneural and neural processes and their plasticity in modulating these functions, in adaptation to tissue injury and pain and in the learning of or rehabilitation of orofacial functions. The mechanisms underlying the articulation of the teeth are also an ongoing and future neuroscience research target."

Sessle added that "given the expanded interest in this field in recent decades and further technological advances undoubtedly to be made in molecular biology, genetics, artificial intelligence, etc., the future holds much promise for further insights into mechanisms underlying these functions and into related processes that account for disorders of these functions. These mechanistic insights will undoubtedly have clinical application in dentistry by enhancing diagnosis and management relevant to disorders affecting these functions."

Credit: 
International Association for Dental, Oral, and Craniofacial Research

Smart buildings face challenges but have plenty of potential

image: Mohamed Ouf: "Occupant-centric controls provide exciting opportunities."

Image: 
Concordia University

We often hear the word "smart" applied to everyday objects: smartphones, smart TVs, smart appliances -- and now, smart buildings.

The idea of the smart building is still young. There is no accepted definition yet, but one of the best examples that illustrates the concept is occupant-centric control (OCC). This involves using data gathered from occupants, the indoor environment and the outdoor climate to optimize occupant comfort and control and energy efficiency.

The building's critical functions -- lighting, heating, AC, window blinds and so on -- would be run by a control system that learns information like room occupancy patterns, light use and temperature adjustment. For buildings with dozens or hundreds of occupants, this can have wide-ranging effects on overall energy costs.

However, while the concept of the smart building is exciting to architects and engineers, it has not yet been widely seen in a real building. There has been research, experimentation and simulations, but overall the implementation of the OCC principle has been unfocussed and inconsistent.

In a new paper published in the journal Building and Environment, Mohamed Ouf looks at case studies in the existing OCC research and assesses the path forward. The paper was co-written with June Young Park at the University of Texas at Austin and colleagues at Carleton University, ETH Zürich and the University of Southern Denmark.

"We scanned the literature for relevant work that has been done on this topic and analyzed its different attributes in detail," says Ouf, an assistant professor in the Department of Building, Civil and Environmental Engineering at the Gina Cody School of Engineering and Computer Science.

"We realized that very few researchers have been able to actually implement these control approaches in real buildings for many logistical reasons."

Ouf is also one of six members of Concordia's new interdisciplinary Smart, Sustainable and Resilient Communities and Cities research team, which aims to come up with solutions to create more sustainable, accessible and inclusive urban spaces. The team, led by Canada Excellence in Research Chair (CERC) Ursula Eicker, is being officially introduced Tuesday, Nov. 12, at Concordia's 4th Space.

Building up the field's foundation

As Ouf and his colleagues point out, research in the field of OCC is still relatively scarce. They identified 120 publications on the topic but only 42 studies included field implementation. Most are conceptual studies or simulations. All of them skewed toward North American or European standards and toward academic or office buildings.

The researchers further identified several challenges facing OCC implementation based on their review of the existing research.

The field's newness means there is still no agreed-upon definition of what the term even means. Does the control approach prioritize occupancy patterns? Or does it focus on occupant behaviour and their interactions with building systems? How much physical control should an occupant have in an automated building? Which metrics -- comfort or energy efficiency -- are prioritized, if either?

Second, OCC's reliance on data means serious technological and privacy issues need to be addressed. The current research largely avoids studies of interconnection between different indoor environments, so a whole-building approach, which will be needed as the field advances, will require significant networking and software development. As well, steps must be taken to ensure occupants' data information is secure.

Given all these avenues of further study, Ouf says he is optimistic about OCC's future.

"This whole niche of occupant-centric controls is still very new and provides exciting opportunities to combine advancements in data science and artificial intelligence with building engineering," he says.

"Luckily, I'm currently establishing a lab at Concordia to implement and experiment with OCC in a real building environment. We will have four offices that are heavily instrumentalized with sensors and actuators to analyze occupant comfort and interactions with building systems. We will also develop new control algorithms with the goal of improving energy efficiency as well as comfort."

Credit: 
Concordia University

Severe pregnancy-related depression may be rooted in inflammation

image: Dr. Eric Achtyes and Dr. Lena Brundin

Image: 
Van Andel Institute

GRAND RAPIDS, Mich. (Nov. 20, 2019) -- A runaway, inflammatory immune response may be responsible for triggering severe depression during and after pregnancy, according to a new study published in the journal Brain, Behavior and Immunity.

Not to be mistaken for the rapidly passing "baby blues," which is common right after delivery, pregnancy-related depression is a serious medical condition that can escalate in severity and may even require hospitalization. One in five new mothers experience depression after pregnancy, with symptoms beginning during pregnancy and generally worsening after delivery. An estimated 14% have suicidal ideation during pregnancy.

"Pregnancy-related depression is common yet poorly understood," said Lena Brundin, M.D., Ph.D., an associate professor at Van Andel Institute and senior author of the study. "Biologically speaking, pregnancy is a major inflammatory event that can upend many of the body's day-to-day molecular processes. If we can better understand these irregularities, it could lead to new ideas about how best to treat perinatal depression."

The team, which included researchers from Pine Rest Christian Mental Health Services and Michigan State University, analyzed blood samples from 165 patient volunteers at Pine Rest's Mother and Baby Program and the Obstetrics and Gynecology Clinic at Spectrum Health in Grand Rapids.

They found that several inflammatory factors appear to contribute to pregnancy-related depression onset and severity. Levels of IL-6 and IL-8 -- both inflammatory chemicals called cytokines -- were elevated while levels of another cytokine called IL-2, which plays an important role in immune function, were low. At the same time, there was a drastic reduction in serotonin, an important chemical regulator of mood.

These changes point to alterations in the way a molecular building block called tryptophan, which is required for serotonin production, is hijacked and shunted away by the kynurenine pathway, a molecular cascade closely linked to inflammation. The resulting loss of serotonin tracks with depressive symptom intensity; the less serotonin, the more severe the symptoms.

"Inflammation is an important and normal part of the immune system and, in early pregnancy, prevents the mother's immune system from attacking the fetus. However, when the inflammatory reaction is protracted or more intense than is optimal, it may lead to worsening depression in a subset of vulnerable women," said Eric Achtyes, M.D., M.S., staff psychiatrist at Pine Rest, an associate professor at Michigan State and the study's lead author. "Hopefully, this study will allow us to develop treatments that more specifically target those who are at risk for an 'inflammatory' perinatal depression."

Credit: 
Van Andel Research Institute

How do gliomas evolve?

image: Cancer researcher Roel Verhaak of The Jackson Laboratory.

Image: 
JAX photo byTiffany Laufer.

Until relatively recently, cancer was viewed as a single disease with sub-types based on where in the body it arose. The advent of detailed molecular analysis has shown that the situation is far more complicated, however, and that there can be many sub-clonal cell populations even within a single tumor. And therein lies a significant problem for effective therapy: eradicating one type of cancer cell may leave another unaffected, and it may actually confer a competitive advantage to it.

The most common malignant brain tumor in adults, diffuse glioma, is also one of the most difficult cancers to treat. It invariably relapses despite surgical, radiotherapeutic and/or chemotherapeutic interventions. But while the initial molecular characteristics have been well described in gliomas, their subsequent evolution under treatment stress remains unknown. To address the problem, an international community of clinicians and researchers established the Glioma Longitudinal Analysis (GLASS) Consortium, which has begun investigating the dynamics of molecular changes in gliomas over time. Their findings to this point, "Longitudinal molecular trajectories of diffuse glioma in adults," are now published in Nature, and they point to highly variable and patient-specific trajectories of genomic alterations in gliomas.

The research team , led by senior author Roel Verhaak, Ph.D., and first authors Floris Barthel, M.D., and Kevin Johnson, Ph.D., at The Jackson Laboratory and including 87 researchers and clinicians from the United States, Europe, Asia and Australia, obtained data for multiple time points from 285 patients treated at 35 hospitals. In the end, the researchers selected high quality tumor samples representing the three major subtypes of diffuse glioma from 222 patients at two time points each, which they characterized as initial and recurrence. The analyses demonstrated the highly variable nature of gliomas, but provide a framework for effective study of glioma evolution and treatment response.

"More data are needed to fully understand glioma evolution, but the GLASS resource provides an excellent foundation to more effectively study both evolution and treatment response," says Verhaak. "Collectively, these findings will help us determine what treatment approaches will result in the greatest removal or killing of glioma cells possible."

Among the interesting findings was that when glioma cells are stressed by cancer therapies such as radiation and chemotherapy, they don't evolve in a consistent manner. There are common features between patient samples, such as hypermutation--a very high rate of mutation in the genome--and aneuploidy, in which entire chromosomes are lost or acquired through cell division dysfunction. But following early events that drive cancer initiation and progression, their evolution often appears to be random instead of proceeding down predictable paths.

The researchers also assessed how immune activity can shape glioma evolution. Immunotherapy, which uses the body's own immune system to target and eliminate cancer cells, is an exciting new field, and understanding immune interactions in the tumor microenvironment and the nature of glioma immune evasion is an important step for possible implementation. The research showed that immune activity (immunoediting) doesn't vary in glioma over time, though there were patient-to-patient differences, and more work is needed to fully understand the variability and what immunotherapy strategies might be most effective for gliomas. On the other hand, the researchers identified a particular mutation in the gene IDH1 that produces a neoantigen--a potential immune system target--and persists through recurrence. The finding provides a possible opening for vaccine treatment at both initial and recurrent stages.

In the end, the effort provides important insight into how to improve the clinical prognosis for glioma patients worldwide.

"The research provides the largest database of sequential glioma tumor profiles to date," says co-author Lucy Stead, Ph.D., from the University of Leeds (UK). " This will offer the research and clinical community the chance to predict how effective new cancer treatments might be at tackling brain tumors."

Credit: 
Jackson Laboratory

Exposure to PM 2.5 pollution linked to brain atrophy, memory decline

Women in their 70s and 80s who were exposed to higher levels of air pollution experienced greater declines in memory and more Alzheimer's-like brain atrophy than their counterparts who breathed cleaner air, according to USC researchers.

The findings of the nationwide study, published today in Brain, touch on the renewed interest in preventing Alzheimer's disease by reducing risk as well as hint at a potential disease mechanism. Alzheimer's is the sixth-leading cause of death in the United States, and there's currently no cure or treatment.

"This is the first study to really show, in a statistical model, that air pollution was associated with changes in people's brains and that those changes were then connected with declines in memory performance," said Andrew Petkus, assistant professor of clinical neurology at the Keck School of Medicine at USC.

"Our hope is that by better understanding the underlying brain changes caused by air pollution, researchers will be able to develop interventions to help people with or at risk for cognitive decline."

Fine particles, also called PM2.5 particles, are about 1/30th the width of a human hair. They come from traffic exhaust, smoke and dust and their tiny size allows them to remain airborne for long periods, get inside buildings, be inhaled easily, and reach and accumulate in the brain. Fine particle pollution is associated with asthma, cardiovascular disease, lung disease and premature death.

Previous research has suggested that fine particle pollution exposure increases the risk for Alzheimer's disease and related dementias. What scientists haven't known is whether PM2.5 alters brain structure and accelerates memory decline.

For this study, researchers used data from 998 women, aged 73 to 87, who had up to two brain scans five years apart as part of the landmark Women's Health Initiative. The Women's Health Initiative was launched in 1993 by the National Institutes of Health and enrolled more than 160,000 women to address questions about heart disease, cancer and osteoporosis.

Those brain scans were scored on the basis of their similarity to Alzheimer's disease patterns by a machine learning tool that had been "trained" via brain scans of people with Alzheimer's disease. The researchers also gathered information about where the 998 women lived, as well as environmental data from those locations to estimate their exposure to fine particle pollution.

When all that information was combined, researchers could see the association between higher pollution exposure, brain changes and memory problems -- even after adjusting to take into account differences in income, education, race, geographic region, cigarette smoking and other factors.

"This study provides another piece of the Alzheimer's disease puzzle by identifying some of the brain changes linking air pollution and memory decline. Each research study gets us one step closer to solving the Alzheimer's disease epidemic," Petkus said.

Credit: 
University of Southern California

Could sphingolipids help solve a racial paradox in heart disease?

image: Dr. Samar Hammad in her laboratory at the Medical University of South Carolina

Image: 
Sarah Pack, Medical University of South Carolina

When it comes to cholesterol, we've come to accept a simple narrative. Our risk of heart disease is lower when we have more "good cholesterol," or high-density lipoproteins (HDL), and less "bad cholesterol," or low-density lipoproteins (LDL) and triglycerides.

Complicating this narrative, however, is the higher risk of severe heart disease in African Americans, despite the fact that they tend to have higher levels of HDL and lower levels of triglycerides.

Researchers at the Medical University of South Carolina (MUSC) explored why it is that African Americans with the autoimmune disease lupus experience severe heart disease while having a lipid profile that would be considered protective in white Americans.

They found that there is more to the lipid story than just HDL, LDL and triglycerides.

The MUSC investigators report in PLOS ONE that another class of lipids, known as sphingolipids, are associated with heart disease in African Americans with lupus.

In autoimmune diseases such as lupus, the body is attacked by its own immune system, which is supposed to defend it against invaders. About 90% of people with lupus are female, and African Americans are three times more likely to have lupus than white Americans. Lupus is a chronic disease that can affect many organs, especially the heart and kidneys. People with lupus are 10 times more likely to have heart disease, which is a leading cause of death for them.

"We know that the African American community has higher HDL, which is a good thing, and lower triglycerides, which is a good thing, but nonetheless, they have more heart disease than the white population," said Samar M. Hammad, Ph.D., associate professor in the Department of Regenerative Medicine and Cell Biology at MUSC and first author of the PLOS ONE article.

"So it is about time to start looking at other molecules and other markers that can explain, at least in part, why African Americans develop more cardiovascular disease," she added. "And that's particularly true in autoimmune diseases such as lupus and Type 1 diabetes."

Hammad thinks that sphingolipid profiles could one day serve as such markers for heart disease in this population.

The MUSC study that she led in collaboration with Jim C. Oates, M.D., director of the Division of Rheumatology and Immunology at MUSC, was the first to look at how race affects sphingolipid levels in patients with lupus and patients with lupus and heart disease.

For the study, Hammad used plasma samples from patients with lupus stored by the MUSC Clinical and Community Resource Core, a part of MUSC's Core Center for Clinical Research (CCCR). The CCCR has collected samples and clinical data over time about hundreds of patients with lupus treated at MUSC, many of them African American.

Hammad and her team analyzed plasma samples from 73 patients with lupus or lupus and cardiovascular disease. She also collected samples from 34 healthy African American and white participants who acted as controls.

Hammad's study found that all patients with lupus, regardless of race, had more sphingolipids than healthy study participants, though the increases were more marked in the African American patients.

Hammad also noted a stark difference in sphingolipid levels between the African American and white patients with lupus who developed heart disease. The levels of sphingoid bases, the backbone on which sphingolipids are created, increased in the African American patients but decreased in the white patients. No other changes in sphingolipids were seen in the white patients, but the African American patients had increases in a number of other sphingolipids as well.

Sphingosine 1-phospahte (S1P) has been shown in previous studies to cause inflammation that can lead to heart disease. In this study, the ratios between certain species of ceramides and S1P were found to be lower in all lupus patients than in healthy participants. These ratios correlated positively with disease activity in African American but not white patients with lupus, as measured by their scores on the Systemic Lupus Erythematosus Disease Activity Index.

"It is interesting that the markers for heart disease in the white patients with lupus are different from those for African Americans," said Hammad.

These differences, according to Hammad, do not, as of yet, add up to a biomarker that physicians could test to see whether someone with early lupus would eventually develop heart disease.

In fact, she doubts that a single biomarker will ever do that job.

However, she thinks that broader information on the types and number of sphingolipids present in a patient's plasma - his or her sphingolipid profile - could one day help physicians to predict disease severity or assess the efficacy of an anti-lupus drug. She also thinks that the ceramide-S1P ratio will likely make up one part of that profile, in much the same way as HDL-LDL ratios are included in lipid profiles today.

Hammad has already participated in research showing that such sphingolipid profiles can be used to predict outcomes in patients with early Type 1 diabetes, another autoimmune disease. These findings were published in the May 2019 issue of the Journal of Clinical Lipidology.

Hammad conducted the study reported in the PLOS ONE article with funding from a pilot project grant from the South Carolina Clinical & Translational Research (SCTR) Institute. SCTR is a Clinical and Translational Science Awards hub headquartered at MUSC and funded by the National Center for Advancing Translational Sciences.

Next, Hammad plans to use these findings to apply for federal funding so that she can test sphingolipid levels in the remainder of the samples in the CCCR patient registry at MUSC. She and Oates will also expand the study to look at other complications of lupus, such as kidney disease.

Credit: 
Medical University of South Carolina

LGBTQ beauty vloggers draw on queer culture to stand out

ITHACA, N.Y. - "Yo! What's up? Welcome back to my channel," Patrick Starrr says in a deep voice, hair wrapped in his signature turban and face in full, elaborate makeup.

Then he returns to his usual, higher-pitched voice. "I am a man," says Starrr, a queer Filipino beauty vlogger whose YouTube channel has 4.5 million subscribers. "I am a man in makeup. I love wearing makeup so much."

Starrr is among the subjects of new Cornell research exploring how a racially diverse group of LGBTQ beauty vloggers navigates seemingly contradictory roles: masculine and feminine; authentic and heavily made up. The vloggers often provide unpaid content to YouTube, but have the potential to enrich themselves; they're vulnerable to harassment, but they also promote the visibility of marginalized people.

At the end of the 2016 video, Starrr removes his makeup and unwraps his turban as the song "You Are So Beautiful" plays.

"Queer people have to work harder in some ways to become successful, but at the same time they have resources they can draw on from queer cultural life to stand out and make a name for themselves," said Katherine Sender, professor of communication in the College of Agriculture and Life Sciences and co-author of "Queer Immaterial Labor in Beauty Videos by LGBTQ-Identified YouTubers," published in October in the International Journal of Communication.

With co-author Ellie Homant, her former advisee at the University of Michigan, Sender studied the YouTube channels of six queer YouTube beauty vloggers, four of whom are people of color, and compared them with six heterosexual beauty vloggers. The researchers examined the vloggers' "Get Ready With Me," paid sponsorship, and personal disclosure videos, and considered 600 comments per vlogger.

"Queer people have to work harder in some ways to become successful, but at the same time they have resources they can draw on from queer cultural life to stand out and make a name for themselves."

Katherine Sender

They pieced together a complex story in which queer vloggers can draw on personal and cultural experiences to seem more authentic - a prized trait among social media influencers, because it makes viewers more likely to trust them and buy the products they recommend.

Coming-out stories, in particular, tend to strike a chord with followers. For example, in a 2015 video Ingrid Nilsen, an Asian and Caucasian female vlogger, says, "There's something that I want you to know: I'm gay [starts to cry]. It feels so good to say that! I'm shaking right now because this moment is here, and it's real." After posting this video, Nilsen gained subscribers and sponsors.

"The coming-out narrative, which has always been part of queer culture, became a strategy that these queer beauty vloggers could use to exemplify a sense of themselves as authentic," Sender said. "Part of it is a genuine commitment to queer visibility, and part of it serves that social media demand to be authentic, credible and relatable."

But it can also be a risky move for LGBTQ vloggers, who receive comments that are often rife with homophobia and transphobia. Vanessa Martinez, a Latina and African American bisexual female vlogger, lost followers and sponsors after her own coming-out video, which was framed by her upbringing in a deeply religious family.

"These people are really putting themselves out there," Sender said, "and part of the emotional labor that they have to do is to absorb, deflect and respond to these hostile statements."

Sender said she was particularly struck by the queer vloggers' success in what might seem like an unlikely realm.

"Beauty culture has traditionally been extremely gendered, with very normative ideas of femininity and what it means to be an attractive woman, and very racially segmented," she said. "So I was really interested to see how these six vloggers went about constructing identities as legitimate and believable beauty experts to a broad audience."

The vloggers tend to be popular across demographics but in a narrow age bracket, comprising mostly teenagers and young adults. Their incomes range widely - from Jeffree Starr, a white gender-nonbinary and sexually nonidentifying beauty vlogger who in 2018 earned an estimated $4 million on YouTube and an additional $14 million in related income, to Nilsen, who earned an estimated $40,000 on YouTube in 2018.

"Some of them are managing to make a very good living, but it's a hard living," said Sender, noting that both the queer and heterosexual vloggers frequently talk about burnout. "There's an assumption that people who do this kind of work are drawn to fame, and there are judgments about narcissism, but I think some of these people got there accidentally and ambivalently. If you want to stay famous, you have to keep at it. But at the same time, people are watching what you do, and they're going to criticize it."

Credit: 
Cornell University

The cause of chewy chicken meat

video: The findings of a new study co-authored by University of Delaware professor Behnam Abasht could provide potential markers to identify chickens that will develop wooden breast syndrome, which makes meat hard and chewy.

Image: 
University of Delaware/ Jeffrey C. Chase

University of Delaware researchers have discovered that lipoprotein lipase, an enzyme crucial for fat metabolism, may be contributing to wooden breast syndrome in broiler chickens.

Wooden breast syndrome can affect broiler chickens, making the meat hard and chewy. It is a costly problem that can render the birds unmarketable, causing significant economic losses for growers, who sometimes see the disease in up to half their flocks.

The UD research team, led by Behnam Abasht, associate professor of animal and food sciences in UD's College of Agriculture and Natural Resources, have identified gene expression irregularities at the onset of wooden breast syndrome that suggest the disease is a metabolic disorder characterized by abnormal fat accumulation in the breast muscle tissue.

The research team reported their results on Wednesday, Nov. 20 in the journal Scientific Reports.

The findings could help drive short-term solutions to help growers manage the condition in chickens at the production level through feed additives or supplements, or to reduce the number of birds that develop the condition.

"The industry desperately needs a solution right now. Conservative estimates project that wooden breast syndrome is costing the U.S. agricultural community $200 million dollars per year, but this number may be much higher," said Abasht.

The United States leads production of broiler chickens worldwide. Delaware has more than 700 producers who raise commercial broiler chickens and over 1,000 small backyard poultry owners. Wooden breast syndrome is a concern around the world, too, as global consumption of chicken has risen in recent years as a leading source of dietary protein.

The research also could inform human health research related to metabolic syndromes, such as diabetes and atherosclerosis, which is associated with fatty deposits in the arteries.

Source of the problem

Abasht has been studying wooden breast syndrome in broiler chickens for nearly a decade. In previous work, his research team analyzed the genes involved in the disease and identified biomarkers for the disorder. They also characterized the unique biochemistry of the hardened breast tissue in chickens with the disease.

In their current work, the UD research team noticed that the expression of lipoprotein lipase was higher in chickens affected with wooden breast syndrome, leading more fat to accumulate in the chicken's pectoral (or breast) muscles. Lipoprotein lipase serves as a "metabolic gatekeeper" that determines how much fat is allowed inside a given tissue.

This was curious because breast muscle fibers in chicken typically rely on sugar (glucose) molecules for fuel, not fat molecules.

The research team used RNA sequencing to determine which genes were being expressed in modern fast-growing broiler chickens and slower-growing legacy chickens. They then employed a new technology, called RNA in situ hybridization, to pinpoint exactly where this gene expression occurred inside the muscle.

The researchers found genetic evidence of lipoprotein lipase being expressed in endothelial cells in chickens, which was previously unknown. Present in all blood vessels, endothelial cells serve as a barrier between the blood and the surrounding tissue.

Abasht hypothesized that when more fat is oxidized for energy in the breast tissue of chickens, it may be causing the excessive release of free radical molecules that would modify (damage) fats and proteins in the muscle, prompting the chicken's immune system to kick in to clear up the problem.

"We observed that if a particular vein was attacked by immune cells, the same vein typically also expressed higher levels of lipoprotein lipase," said Abasht.

The researchers went a step further and compared this data with the gene expression signals found in two commercial broiler chicken lines, at three weeks of age and again at market age. In their analysis, the researchers found signals consistent with the fact that young chickens may be showing the same changes as market-age broiler chickens with wooden breast syndrome, even before the disease shows up.

The findings could provide potential markers to identify chickens that will develop the disease.

In recently published research in Genes, the researchers also reported finding common features between wooden breast syndrome in chickens and diabetes complications in humans, specifically diabetic cardiomyopathy, a chronic disease characterized by molecular and structural changes in the heart muscle.

Abasht's research team is currently combing available literature for treating diabetes to see if there are ways to apply similar approaches to help broiler chickens avoid -- or cope -- with wooden breast syndrome, through diet, supplements or medication.

If they can find common solutions, Abasht said, a far-reaching goal of the work might be to use chickens as a model to study possible treatments for diabetes in humans.

"Our main focus was to address this problem from an agricultural perspective, but our findings open new horizons for future research that could benefit both agriculture and human health. This is a very interesting prospect for us," said Abasht.

Longer term, Juniper Lake, a UD doctoral student in Abasht's lab, said that having a deeper understanding of the genetic causes behind the disease could lead to solutions for agricultural producers to selectively breed out the traits that cause wooden breast disease, which has a relatively high heritability.

"There's a lot to be gained from basic research of wooden breast, even if the main goal is to mitigate economic losses in the poultry industry," said Lake.

Credit: 
University of Delaware

Tiny filters help detect cancerous blood cells

image: Simulations showing cancerous multiple myeloma cells, also known as cCPCs, getting stuck between micropillars in a new filter device, described in Biomicrofluidics. Blue outline is the cCPC and fluid is flowing is from top to bottom.

Image: 
Lidan You, University of Toronto

WASHINGTON, D.C., November 19, 2019 -- Multiple myeloma is a type of blood cancer in which malignant plasma cells, a type of white blood cell, accumulate in the bone marrow. This leads to bone destruction and failure of the marrow, which in healthy individuals, produce all the body's red blood cells. The most recent data from the American Cancer Society estimates that almost 27,000 new cases of MM are diagnosed every year, and of these, over 11,000 patients died.

Recent studies have shown some myeloma cells can leave the bone marrow and enter the blood stream. The presence of these cells, known as clonal circulating plasma cells, or cCPCs, in the blood has been correlated with shorter survival times.

Until now, it has been difficult to detect cCPCs in the blood. Existing methods cannot always detect the low levels of these cells in MM patients. In this week's issue of Biomicrofluidics, from AIP Publishing, investigators report the development of a new device that can detect and isolate cCPCs from small samples of blood.

The device is a type of filter that separates malignant plasma cells from normal ones. It is based on a concept known as microfluidics. The filtering action is due to tiny pillars in the flow channel, designed in a precise way that allows normal blood cells through the filter while capturing the cancerous cCPCs.

The scientists who developed this device used a computational model to consider circular-, square- and diamond-shaped pillars of various sizes for their design. Their computer model showed the diamond shape provided a low resistance to flow. They also found by adjusting the diamond shape so that the pillars were longer and more pointed, the filtering action was improved.

Red blood cells are the smallest cells in blood plasma, with diameters in the range of 6-8 microns. White blood cells (WBCs) are bigger, with diameters ranging from 7 to 30 microns. While the cancerous cCPCs are large, with a size of 30-50 microns, the smallest cCPCs are about the same size as the largest WBCs. However, WBCs can deform and squeeze between the tiny pillars. The cCPCs are stiffer and cannot deform this way, so they end up stuck in the filter.

Studies were carried out with cultured cancer cells as well as on blood samples from patients with MM. The amount of cCPCs captured from patients with active MM was much higher than from patients in remission or from healthy individuals. Co-author Lidan You said, "This device shows great potential as a noninvasive method for either early detection or monitoring of MM disease progression."

Credit: 
American Institute of Physics

Study identifies barriers high schools face when implementing, enforcing concussion laws

All 50 U.S. states enacted concussion laws between 2009-2014 to mitigate the consequences of concussion. While details of the laws vary from state to state, all state laws address three main factors: concussion education; removal from play after suspected concussion; and return-to-play requirements.

A new study conducted by researchers at the Center for Injury Research and Policy in the Abigail Wexner Research Institute (AWRI) at Nationwide Children's Hospital investigated the barriers high schools across the country face when implementing state concussion laws.

The study, published today in Journal of Adolescent Health, found that many high schools reported challenges implementing and enforcing the three main parts of state concussion laws. Athletic trainers noted in interviews that the concussion education materials currently available often used complex medical terms, did not require active learning, and were often not available in needed languages. In addition, athletic trainers noted a lack of buy-in to state law requirements from both coaches and parents, who may not understand the potential severity of these injuries, which, in turn, made scheduling a time for this training and full compliance with school concussion policies challenging.

"Our hope is that school administrators, athletic directors, and athletic trainers can use these findings to identify implementation barriers in their own schools," said Ginger Yang, PhD, MPH, senior author of the study and principal investigator in the Center for Injury Research and Policy at Nationwide Children's. "These findings can help high schools structure their school's policies to maximize the safety of student-athletes and shed light on necessary updates and revisions to current state-level concussion laws."

The barriers to removal from play were associated with athletes' attitudes towards concussion and concussion reporting as well as their unwillingness to disclose concussion symptoms, and resistance from coaches and parents. Sports culture and "old school" mentality of parents and coaches that encourage athletes to "play through it" and "toughen up" can create an environment that is not conducive to athletes reporting symptoms. Lack of an effective system for communicating across all levels was also noted, especially when a concussion occured during an away game.

"It is imperative that parents, athletes and coaches understand and follow their school's concussion policy. It's better to sit out for a game than to get injured worse and miss the rest of the season," said Sean Rose, MD, pediatric sports neurologist and co-director of the Complex Concussion Clinic at Nationwide Children's. "Athletic directors, school administrators and athletic trainers can help create an environment that focuses on the safety of the kids and encourages the disclosure of concussion symptoms and immediate removal from play following an actual or suspected concussion."

Barriers to return-to-play centered on policy-level influences, including high costs of and limited access to medical treatment and lack of clarity or specification in state laws regarding which medical professionals can, or should, provide return-to-play clearance. The importance of athletes being treated by a medical professional with up-to-date concussion-specific medical training is desired, but access to these professionals can be disproportionally challenging for some athletes.

Policy-makers can use these findings to update current state concussion laws, clarify return-to-play language, and include ways for athletes who face sociocultural or economic barriers to be cleared to safely return-to-play. By identifying intrapersonal, interpersonal, organizational and policy-level barriers to the implementation of state concussion laws at the school level, effective implementation strategies can be developed to increase the public health impact of these laws.

Credit: 
Nationwide Children's Hospital

Evidence in mice that childhood asthma is influenced by the neurotransmitter dopamine

Neurons that produce the neurotransmitter dopamine communicate with T cells to enhance allergic inflammation in the lungs of young mice but not older mice, researchers report November 19 in the journal Immunity. The findings potentially explain why asthma susceptibility is higher in children than in adults. By highlighting the important role of interactions between the nervous system and the immune system in childhood asthma, the results could lead to new strategies for treating the common chronic disease.

"This is the first study that reveals a contribution of age-related nerve-T cell communication to susceptibility to the development of asthma in young children," says senior study author Xingbin Ai, a Harvard researcher at Brigham & Women's Hospital and Massachusetts General Hospital. "Since asthma often starts in early childhood, we believe that the identification of disease mechanisms unique to young age will provide novel therapeutic targets for early intervention of asthma."

Asthma is a potentially life-threatening chronic condition that intermittently inflames and narrows the airways in the lungs, causing wheezing, chest tightness, shortness of breath, and coughing. Although medical treatment and management of environmental triggers can help control symptoms, there is currently no cure for the disease. In the United States, asthma affects more than 26 million people, including an estimated 6 million children. In fact, it is one of the most common long-term diseases of childhood.

Ai and colleagues suspected that the nervous system, which communicates with the immune system to regulate inflammation, might explain the high prevalence of asthma in children. As the nervous system continues to develop after birth, neurons may modulate tissue inflammation in an age-related manner.

In the new study, Ai and colleagues investigated the role of the developing nervous system in asthma characterizing early age. The researchers discovered that sympathetic nerves innervating the mouse lung primarily produced dopamine in early postnatal life but another neurotransmitter called norepinephrine in adult life. A similar pattern was evident when they compared lung and lymph node tissues from children up to 13 years of age and adults ranging in age from 40 to 65 years.

In addition, the researchers found that dopamine released by sympathetic nerves innervating the lung binds to the dopamine neurotransmitter receptor on CD4+ T helper cells to promote their differentiation into asthma-exacerbating Th2 cells, thereby enhancing lung inflammation. By contrast, norepinephrine-producing nerves in the adult lung had no such effect. Importantly, the findings reveal the similarity between mice and humans in terms of the innervation of dopamine-producing nerves in the early lung and the T cell response to dopamine.

In mouse models of allergen exposure, the dopamine-DRD4 pathway significantly increased Th2 cell inflammation in the lung tissue of neonatal mice, reducing mucus overproduction and airway hyper-responsiveness. By contrast, these effects were either not evident or much weaker in adult mice exposed to allergens.

Taken together, these findings demonstrate that the dopamine-DRD4 signaling between sympathetic nerves and CD4+ T helper cells in the lung plays an important role in augmenting allergic inflammation in early life. By facilitating inflammation, dopamine-producing nerves may endow the early lung with a mechanism of tissue repair following infection, which may be advantageous when the lung is immature and vulnerable to pathogens.

"Our findings provide evidence for the involvement of the communication between nerves and immune cells in susceptibility to asthma in early life," Ai says. "It is important to emphasize that simply generically blocking the nerve-immune cell communication is not a good solution, as nerves play important roles in regulating functions of the airway, such as breathing. We will need to identify more specific pathways along the nerve-immune cell axis for therapeutic targeting."

Toward this goal, the researchers will set out to identify druggable targets to disrupt the nerve-T cell communication that goes awry upon allergen exposure. They will also evaluate whether this age-related communication impacts the progression of asthma from childhood to adulthood, and if so, how disease progression can be prevented. Another avenue of future research will be to investigate how allergen exposure and viral infection may affect nerve development in the lung, thereby triggering asthma in children.

"We hope our findings can be used to facilitate the discovery of specific biomarkers for the identification of allergic asthma in children and to predict the severity and progression of the disease," Ai says. "In addition, targeting the communication between sympathetic nerves and CD4+ T cells via the dopamine-DRD4 pathway may be a strategy to battle the increasing prevalence of allergic asthma in children."

Credit: 
Cell Press

Brain scans reveal how the human brain compensates when one hemisphere is removed

video: A view of a structural magnetic resonance image (MRI, axial orientation) showing slices from the top to the bottom of the brain of an adult who had one complete hemisphere resected in childhood due to epilepsy. Global interhemispheric connectivity remains intact, yet with increased connectivity between networks, supporting cognition despite atypical brain anatomy.

Image: 
Caltech Brain Imaging Center

Researchers studying six adults who had one of their brain hemispheres removed during childhood to reduce epileptic seizures found that the remaining half of the brain formed unusually strong connections between different functional brain networks, which potentially help the body to function as if the brain were intact. The case study, which investigates brain function in these individuals with hemispherectomy, appears November 19 in the journal Cell Reports.

"The people with hemispherectomies that we studied were remarkably high functioning. They have intact language skills; when I put them in the scanner we made small talk, just like the hundreds of other individuals I have scanned," says first author Dorit Kliemann, a post-doc at the California Institute of Technology. "You can almost forget their condition when you meet them for the first time. When I sit in front of the computer and see these MRI images showing only half a brain, I still marvel that the images are coming from the same human being who I just saw talking and walking and who has chosen to devote his or her time to research."

Study participants, including six adults with childhood hemispherectomy and six controls, were instructed to lay down in an fMRI machine, relax, and try not to fall asleep while the researchers tracked spontaneous brain activity at rest. The researchers looked at networks of brain regions known to control things like vision, movement, emotion, and cognition. They also compared the data collected at the Caltech Brain Imaging Center against a database of about 1,500 typical brains from the Brain Genomics Superstruct Project.

They thought they might find weaker connections within particular networks in the people with only one hemisphere, since many of those networks usually involve both hemispheres of the brain in people with typical brains. Instead, they found surprisingly normal global connectivity--and stronger connections than controls between different networks.

All six of the participants were in their 20s and early 30s during the study, but they ranged from 3 months old to 11 years old at the time of their hemispherectomies. The wide range of ages at which they had the surgeries allowed the researchers to home in on how the brain reorganizes itself when injured. "It can help us examine how brain organization is possible in very different cases of hemispherectomy patients, which will allow us to better understand general brain mechanisms," says Kliemann.

Moving forward, the hemispherectomy research program at Caltech, led by Lynn Paul (senior research scientist and principal investigator) in the laboratory of Ralph Adolphs (Bren Professor of Psychology, Neuroscience, and Biology and the director of the Caltech Brain Imaging Center) hopes to replicate and expand this study in order to better understand how the brain develops, organizes itself, and functions in individuals with a broad range of brain atypicalities.

"As remarkable as it is that there are individuals who can live with half a brain, sometimes a very small brain lesion like a stroke or a traumatic brain injury like a bicycle accident or a tumor can have devastating effects," says Kliemann. "We're trying to understand the principles of brain reorganization that can lead to compensation. Maybe down the line, that work can inform targeted intervention strategies and different outcome scenarios to help more people with brain injuries."

Credit: 
Cell Press

Trial compares maternal blood loss with immediate vs. delayed umbilical cord clamping

What The Study Did: This randomized clinical trial compared maternal blood loss with immediate umbilical cord clamping (within 15 seconds after birth) versus delayed clamping (60 seconds after birth) in 113 women who had a scheduled cesarean delivery at term of 37 weeks or more.

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

Authors: Cynthia Gyamfi-Bannerman, M.D., M.Sc., of the Columbia University Irving Medical Center in New York, is the corresponding author.

(doi:10.1001/jama.2019.15995)

Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Credit: 
JAMA Network

Ayahuasca compound changes brainwaves to vivid 'waking-dream' state

image: These are brainwaves measured by EEG under control conditions.

Image: 
Imperial College London, Chris Timmermann

Scientists have peered inside the brain to show how taking DMT affects human consciousness by significantly altering the brain's electrical activity.

DMT (or dimethyltryptamine) is one of the main psychoactive constituents in ayahuasca, the psychedelic brew traditionally made from vines and leaves of the Amazon rainforest. The drink is typically prepared as part of a shamanic ceremony and associated with unusual and vivid visions or hallucinations.

The latest study is the first to show how the potent psychedelic changes our waking brain waves - with researchers comparing its powerful effects to 'dreaming while awake'.

The work, led by researchers from the Centre for Psychedelic Research at Imperial College London and published today in the journal Scientific Reports, may help to explain why people taking DMT and ayahuasca experience intense visual imagery and immersive 'waking-dream' like experiences.

DMT is a naturally occurring chemical found in miniscule amounts in the human brain but also in larger amounts in a number of plant species around the world.

Accounts from people who have taken DMT report intense visual hallucinations often accompanied by strong emotional experiences and even 'breakthroughs' into what users describe as an alternate reality or dimension.

But scientists are interested in using the powerful psychoactive compound for research as it produces relatively short but intense psychedelic experiences, providing a window for collecting data on brain activity when consciousness is profoundly altered.

In the latest study, the Imperial team captured EEG measures from healthy participants in a clinical setting, in a placebo-controlled design.

A total of 13 participants were given an intravenous infusion of DMT at the National Institute for Health Research (NIHR) Imperial Clinical Research Facility.

Volunteers were fitted with caps with electrodes to measure the brain's electrical activity, before, during and after their infusion, with the peak of the psychedelic experience lasting around 10 minutes.

Analysis revealed that DMT significantly altered electrical activity in the brain, characterised by a marked drop off in alpha waves - the human brain's dominant electrical rhythm when we are awake. They also found a short-lived increase in brainwaves typically associated with dreaming, namely, theta waves.

In addition to changes in the types of brainwaves, they also found that, overall, brain activity became more chaotic and less predictable - the opposite to what is seen in states of reduced consciousness, such as in deep sleep or under general anaesthesia.

"The changes in brain activity that accompany DMT are slightly different from what we see with other psychedelics, such as psilocybin or LSD, where we see mainly only reductions in brainwaves," said lead author Christopher Timmermann, from the Centre for Psychedelic Research.

"Here we saw an emergent rhythm that was present during the most intense part of the experience, suggesting an emerging order amidst the otherwise chaotic patterns of brain activity. From the altered brainwaves and participants' reports, it's clear these people are completely immersed in their experience - it's like daydreaming only far more vivid and immersive, it's like dreaming but with your eyes open."

Mr Timmermann explains that while it's unclear as to whether DMT may have any clinical potential at this stage, the group hopes to take the work further by delivering a continuous infusion of DMT to extend the window of the psychedelic experience and collect more data.

The team says future studies could include more sophisticated measurements of brain activity, such as fMRI, to show which regions and networks of the brain are affected by DMT. They believe the visual cortex, the large area towards the back of the brain, is likely to be involved.

Dr Robin Carhart-Harris, head of Centre for Psychedelic Research, said: "DMT is a particularly intriguing psychedelic. The visual vividness and depth of immersion produced by high-doses of the substance seems to be on a scale above what is reported with more widely studied psychedelics such as psilocybin or 'magic mushrooms'.

"It's hard to capture and communicate what it is like for people experiencing DMT but likening it to dreaming while awake or a near-death experience is useful.

"Our sense it that research with DMT may yield important insights into the relationship between brain activity and consciousness, and this small study is a first step along that road."

Credit: 
Imperial College London