Culture

Legacy pollutants found in migratory terns in Great Lakes region

image: University at Buffalo researcher Steven Travis cracks an abandoned tern egg into a beaker. Though the new study published in Environment International focuses on common tern chicks, juveniles and adults, Travis and colleagues have begun work on a study examining the levels of pollutants in the eggs of common terns and other wild aquatic birds.

Image: 
Meredith Forrest Kulwicki / University at Buffalo

BUFFALO, N.Y. -- Chemicals that haven't been manufactured in the U.S. for years or even decades are still turning up in the bodies of migratory terns in the Great Lakes region, a new study finds.

The research focused on three types of compounds: polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and the breakdown products, called metabolites, of dichlorodiphenyltrichloroethane (DDT).

Scientists discovered all three kinds of chemicals in the organs of over two dozen common terns in breeding grounds along the Niagara River and the shore of Lake Erie. The pollutants were found at various life stages, in chicks, in juveniles and in adults.

Researchers also detected the compounds in emerald shiners, a small fish that is the terns' primary food source in the area.

The research was published online on Sept. 3 in Environment International, and will appear in the journal's November issue. Authors included University at Buffalo chemists Diana Aga and Steven Travis, and SUNY Buffalo State biologist Alicia Pérez-Fuentetaja.

Sales of PBDEs, a class of flame retardants used in car seats, carpet padding, mattresses and many other household products, were phased out in the U.S. in 2013. Production of PCBs, once widely used as a coolant or insulating fluid in electrical transformers and capacitators, ended in the country in 1979. And use of DDT, an insecticide, has been prohibited in the U.S. for almost half a century, since 1972. The metabolite of DDT that the team found in the birds and fish is called dichlorodiphenyldichloroethylene (DDE).

"These chemicals are still there. They don't just go away. With PCBs, for example, they haven't been produced in the U.S. for a long time now, but you can still find them in the environment, in sediments and in water. They don't degrade for many years. The fish eat organisms that accumulate them, and then the birds eat the fish," says Aga, PhD, Henry M. Woodburn Professor of Chemistry in the University at Buffalo College of Arts and Sciences.

"The common tern is a threatened species in New York State, and their numbers have not increased much despite state efforts to provide nesting sites and surveillance. This study shows how wildlife is affected by human pollution of aquatic systems and how the chemicals we produce can have a multigenerational effect, being passed from mothers to chicks," says Pérez-Fuentetaja, PhD, Professor of Biology at SUNY Buffalo State and Research Scientist at the Great Lakes Center at SUNY Buffalo State.

The levels of PCBs and PBDEs in the birds were high enough to potentially harm the birds' health and affect population recovery, the authors write in their paper.

Pollutants impact terns in every stage of life

The findings illustrate how household and industrial chemicals have become ubiquitous in the environment, where they can endure for many years, posing risks to wildlife.

In the case of terns, the threat begins from the earliest moments of their lives, even before they hatch, says Travis, the paper's first author, who successfully defended his PhD thesis at UB this fall.

He notes that the smallest chicks the team studied harbored higher concentrations of the chemicals than older birds and adults, indicating that the compounds are being passed from parent to progeny. To test this hypothesis, Travis has begun work on a study examining the levels of pollutants in the eggs of common terns and other wild aquatic birds.

"We see these really high concentrations in the smaller chicks, which indicates that there is maternal transfer of contaminants into the eggs," he says.

"These substances interfere with the reproductive system and are endocrine disruptors," Pérez-Fuentetaja says. "They tax the terns' livers as they have to try and get rid of these pollutants, but the bioaccumulative nature of PCBs, PBDEs and DDEs means that the birds will not be able to fully detoxify themselves, and that they will pass part of their body-load to the next generation. These substances can alter development and neurological processes and could cause deformities, cancers and impaired behavior."

The research highlights the risks associated with legacy contaminants, as well as the urgency of protecting the environment as new issues surrounding other classes of persistent chemicals, such as per- and polyfluoroalkyl substances (PFAS), emerge. Aga says that once persistent pollutants become pervasive in water and soil, it's very difficult to get rid of them.

The new study shows how long-banned chemicals continue to jeopardize the health of Great Lakes ecosystems.

"We can't say that all the chemicals we're seeing in the birds are coming from the Great Lakes, as the birds migrate and could be accumulating these compounds in other places along their migration route, too," Travis says. "But the specific types of PCBs and PBDEs we're seeing in the emerald shiners is similar to what we're seeing in the birds. This pattern of chemical concentrations suggests that pollution in the Great Lakes region is the source of at least some of this contamination."

He adds, however, that, "One positive outcome of the study is that we only see the metabolite of DDT, called 'DDE,' in the fish. This likely indicates that there aren't new sources of DDT being introduced to Lake Erie and the Niagara River, and that the DDT that was there is breaking down."

Credit: 
University at Buffalo

It's all about the right balance

image: Surrealistic take on the enzyme UBE2S, which regulates its lifetime by switching between a monomeric and a dimeric state.

Image: 
© Anna Liess

During cell division specific target proteins have to be turned over in a precisely regulated manner. To this end specialized enzymes label the target proteins with signaling molecules. However, the enzymes involved in this process can also label themselves, thus initiating their own degradation. In a multidisciplinary approach, the researchers identified a mechanism of how enzymes can protect themselves from such self-destruction and maintain sufficient concentrations in the cell. These results have been published in the latest issue of Science Signaling.

Vital functions of the multicellular organisms, such as growth, development, and tissue regeneration, depend on the precisely controlled division of cells. A failure in the underlying control mechanisms can lead to cancer. A team of researchers led by Dr. Sonja Lorenz from the Rudolf Virchow Center - Center for Integrative and Translational Bioimaging at the University of Würzburg and by Dr. Jörg Mansfeld from the Biotechnology Center (BIOTEC) at the Technical University of Dresden discovered a new mechanism that modulates cell division.

Ubiquitination - a central regulatory element

A critical step in cell division is the distribution of the genetic information evenly between the daughter cells. This process is controlled by a large protein complex, the anaphase-promoting complex/cyclosome (APC/C), which labels proteins with a signaling molecule known as "ubiquitin". The ubiquitin label functions essentially as a molecular postal code, targeting labeled proteins to the cellular protein degradation machinery. To allow for the efficient and precise labeling of target proteins, the APC/C works together with an ubiquitin-conjugating enzyme, UBE2S. However, UBE2S also has the ability to modify itself with ubiquitin, thus initiating its own degradation. This ability applies to ubiquitination enzymes in general. "This raises the fundamental question of how ubiquitination enzymes find the right balance between labeling their targets and labeling themselves to ensure that sufficient quantities of the enzymes are available in the cell," says Sonja Lorenz.

Switching between active and inactive states

The new study provides an answer to this question by showing that UBE2S can adopt an inactive state in which it is unable to label itself with ubiquitin. "When UBE2S forms a dimer, i.e., two molecules pair with each other, they become inactive and protected from self-destruction," says Jörg Mansfeld. The scientists suggest that this mechanism ensures that a stable cellular pool of UBE2S is preserved and re-activated when required. The cell can thus control the ratio of active and inactive UBE2S to fine tune cell division. These findings provide a structural framework for the development of new cancer-therapeutic strategies and drug discovery.

Ubiquitin research in the Lorenz and Mansfeld groups

The current study presents the second successful, published collaboration of the Lorenz and Mansfeld groups on the regulation of UBE2S. Notably, both research articles were featured in dedicated commentary pieces.

The research group of Sonja Lorenz investigates the structural basis of the ubiquitin system, which controls almost all cellular processes. She is particularly interested in revealing the factors that account for the enormous specificity of ubiquitin as a molecular signal. Her group combines high-resolution structural techniques that yield atomic-resolution views with biochemical, biophysical, and cell-based methods. The Lorenz laboratory is funded by the Emmy Noether program of the German Research Foundation (DFG) and an ubiquitin-focused Research Training Group (GRK2243; DFG), which Sonja Lorenz represents as a co-speaker. Sonja Lorenz is also a founding member of the Mildred Scheel Early Career Center (German Cancer Aid) in Würzburg and has been engaged with transregional ubiquitin initiatives. In 2018 Dr. Lorenz was accepted into the highly selective EMBO Young Investigator Program. A member of the Lorenz laboratory, Anna Liess was part of the Würzburg Graduate School of Life Sciences and the GRK2243 and successfully defended her PhD thesis in 2020.

Jörg Mansfeld and his research group focus on ubiquitination and other protein modifications. The Mansfeld group uses cell biology and biochemical methods to investigate the role of these modifications in the decision whether a cell continues to divide or stops, in order to fulfill a specialized function. The Mansfeld group is funded by the ERC under the European Union's Horizon 2020 research and Innovation Program as well as Emmy Noether and project grants of the DFG. Alena Kučerová is a PhD student of the Dresden International Graduate School for Biomedicine and Bioengineering (DIGS-BB) and was supported by a DIGS-BB Fellowship.

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Technische Universität Dresden

Delivering proteins to testes could someday treat male infertility

image: Delivering a protein (red fluorescence) to mice testes with a fibroin nanoparticle-encapsulated cationic lipid complex (green) restored male fertility.

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Adapted from <i>ACS Nano</i> <b>2020</b>, DOI: 10.1021/acsnano.0c04936

According to the Mayo Clinic, about 15% of couples are infertile, and male infertility plays a role in over one-third of these cases. Often, problems with sperm development are to blame. Now, researchers reporting in ACS Nano have found a way to deliver a protein important for sperm cell production directly to mouse testicles, where it restored normal sperm development and allowed previously infertile mice to father pups.

Male infertility often happens because of a lack of sperm in the semen, which can result from damage to the blood-testis barrier (BTB). This barrier protects reproductive cells from harmful toxicants and drugs, and a protein called PIN1 is important for its function. Mice genetically engineered to lack PIN1 are infertile, with small testes, depleted sperm stem cells and a low sperm count. Although scientists have considered gene therapies to treat male infertility, these procedures are risky because they could cause unwanted genetic changes in reproductive cells that might be passed onto offspring. Hyun-Mo Ryoo and colleagues wanted to develop a system to deliver proteins (such as PIN1) instead of genes to the testes, but first they had to find a way to get proteins through the complex tubes of the testicles and into cells.

The researchers developed a delivery system called Fibroplex, which consisted of spherical nanoparticles made of silk fibroin and a coating of lipids. They loaded PIN1 into Fibroplex, and showed that the particles appeared safe and didn't show signs of toxicity or testicular damage in mice. When the team injected the PIN1-loaded Fibroplex into the testes of young mice with PIN1 deletions, the treatment restored nearly normal PIN1 levels and sperm stem cell numbers and repaired the BTB. Treated mice had normal testicular weight and size and about 50% of the sperm count of wild-type mice. Until about 5 months after treatment, when the protein degraded, the PIN1-Fibroplex-treated mice fathered a similar number of pups as wild-type mice, whereas untreated mice with PIN1 deletions remained infertile. This is the first demonstration of direct delivery of proteins into the testis to treat male infertility, the researchers say.

Credit: 
American Chemical Society

Journal calls for use of objective data in root cause analyses of adverse medical events

image: Dr. Farrokh Alemi calls for moving past Root Cause and Failure Mode analysis in hospital risk management as they are unsupported by data.

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George Mason University

Wrong-site surgery, medication errors, and fires in operating rooms can be devastating for patients, providers, hospitals, and insurance companies alike. In risk management, these are referred to as sentinel adverse events. Determining the true causes of these events can help hospitals improve their processes, leading to large impacts on costs and outcomes of care. Typically, hospital risk managers and improvement teams do this through either Root Cause or Failure Mode analysis—both methods that can only point to possible causes and that do not look at patterns over time or across sites.

In an editorial in the Quality Management in Healthcare journal, Dr. Farrokh Alemi calls for moving past these methods, as they are unsupported by data. Dr. Alemi is a professor of health informatics in the George Mason University’s College of Health and Human Services. He is a national thought leader on statistical methods relevant for quality improvement.

“Relying on clinicians’ insights for understanding root causes has not worked well. It has perpetuated the system that produces these events. What is needed is objective data that can provide fresh insights into causes of these events,” adds Alemi. “Risk managers need to rethink their case-by-case reasoning about adverse events and examine patterns across these events. Only then they can understand true underlying causes of adverse events.”

While individual events should still continue to be reviewed, it’s important that risk managers look at patterns of data across cases. The editorial has called for use of modern causal analysis to produce new insights into why sentinel adverse events keep reoccurring.

To help risk managers orient themselves to modern causal analysis, several articles in the special issue demonstrate different methods of relying on objective data. In the special issue, Alemi also authored a causal network tutorial. The tutorial shows how improvement teams and risk managers can create data-based causal networks through repeated use of regression analysis. This method can more reliably identify the root cause of adverse events rather than just possible causes.

“Unlike in some other industries, we continue to see adverse events happening at a high rate in health care,” explains Alemi. “We actually have an opportunity to prevent them, and that is promising. This tutorial shows how risk managers can use tried-and-true statistical methods to see which factors are actually causing these adverse events so they can prioritize addressing the factors that will reduce these events.”

In his tutorial, Alemi gives step-by-step instructions for conducting a type of multivariate regression analysis—a least absolute shrinkage and selection operator (LASSO) regression to create a causal network. Once the LASSO regression is completed, the findings must be tested and then the parameters of the network are determined through analysis of objective data. The method objectively identifies causes of adverse events.

The journal’s special section also includes articles by a number of authors analyzing adverse events in operating rooms, blood administration, and treatments that diminish the risk of blot clots. A review article shows the history of development of causal networks and how these methods may be relevant to risk managers.

About George Mason University

George Mason University is Virginia's largest and most diverse public research university. Located near Washington, D.C., Mason enrolls 39,000 students from 130 countries and all 50 states. Mason has grown rapidly over the past half-century and is recognized for its innovation and entrepreneurship, remarkable diversity and commitment to accessibility. For more information, visit https://www2.gmu.edu/.

About the College of Health and Human Services

George Mason University's College of Health and Human Services prepares students to become leaders and shape the public's health through academic excellence, research of consequence, community outreach, and interprofessional clinical practice. George Mason is the fastest-growing Research I institution in the country. The College enrolls 1,918 undergraduate and 1,371 graduate students in its nationally-recognized offerings, including: 5 undergraduate degrees, 13 graduate degrees, and 7 certificate programs. The college is transitioning to a college public health in the near future. For more information, visit https://chhs.gmu.edu/.

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George Mason University

Study discovers potential target for treating aggressive cancer cells

PROVIDENCE, R.I. [Brown University] -- As researchers and medical professionals work to develop new treatments for cancer, they face a variety of challenges. One is intratumor heterogeneity -- the presence of multiple kinds of cancer cells within the same tumor. Often, these "mosaic" tumors include cells, such as polyploidal giant cancer cells, that have evolved to become aggressive and resistant to chemotherapy and radiation.

In the past, polyploidal giant cancer cells (PGCCs) have been largely ignored because studies had found that they do not undergo mitosis, which is the mechanism that is typically required for cell division. However, recent studies have found that PGCCs undergo amitotic budding -- cell division that does not occur through mitosis -- and that their cell structure enables them to spread rapidly.

A new study, published this month by a team of Brown University scientists in Proceedings of the National Academy of Sciences, sheds more light and identifies a potential target for treating these aggressive cancer cells.

Specifically, PGCCs rely on cell filaments called vimentin in order to migrate. Vimentin is found in cells throughout the body, but PGCCs were found to have a greater amount of vimentin compared to non-PGCC control cells, and their vimentin was much more evenly distributed throughout the cell.

"These cells appear to play an active role in invasion and metastasis, so targeting their migratory persistence could limit their effects on cancer progression," said study author Michelle Dawson, an assistant professor of molecular pharmacology, physiology and biotechnology at Brown University.

As cells replicate within a tumor, they become increasingly crowded, and neighboring cells press tightly against them. Eventually, the cells become jammed together in a solid-like mass. Vimentin provides PGCCs with a more flexible, elastic structure, which helps protect them from damage in this situation and allows them to squeeze past their neighboring cells to escape to new, less crowded areas.

Thus, when the researchers disrupted vimentin, they dramatically reduced the cells' ability to move. In addition, vimentin appears to play an important role in rearranging the nucleus of a dividing cell, so vimentin disruption could also help prevent PGCCs from forming daughter cells.

As a next step, Dawson and her colleagues hope to find a biomarker for PGCCs so that they can study these cells in human tumors.

"This study shows vimentin is overexpressed in PGCCs and is likely responsible for several of their abnormal behaviors," Dawson said. "Vimentin is a ubiquitous protein, so targeting vimentin directly may not be an answer, but drugs that target vimentin interactions may be effective in limiting the effects of these cells."

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Brown University

Community noise may affect dementia risk

Results from a new study published in Alzheimer's & Dementia support emerging evidence suggesting that noise may influence individuals' risk of developing dementia later in life.

Researchers studied 5,227 participants of the Chicago Health and Aging Project who were aged 65 years or older, of whom 30% had mild cognitive impairment and 11% had Alzheimer's disease. They found that persons living with 10 decibels more noise near their residences during the daytime had a 36% higher odds of having mild cognitive impairment and a 30% higher odds of having Alzheimer's disease.

"These findings suggest that within typical urban communities in the United States, higher levels of noise may impact the brains of older adults and make it harder for them to function without assistance. This is an important finding since millions of Americans are currently impacted by high levels of noise in their communities," said senior author Sara D. Adar, ScD, of the University of Michigan School of Public Health, Ann Arbor. Professor Adar added that "although noise has not received a great deal of attention in the United States to date, there is a public health opportunity here as there are interventions that can reduce exposures both at the individual and population level."

The study was supported by grants from the Alzheimer's Association and the National Institute on Aging.

Credit: 
Wiley

Researchers analyze studies of interventions to prevent violence against children

Numerous studies have examined interventions aimed at preventing violence against children. A recent analysis reveals various gaps not adequately addressed by these studies.

The analysis, published in Campbell Systematic Reviews, points to the need for more quantitative and qualitative research to assess the effectiveness of interventions to combat violence against children, with attention to expand studies to different regions of the world and to analyze interventions targeting specific forms of violence.

"Sharing and discussing these findings with policy makers and other key actors is necessary for a coordinated approach to filling knowledge gaps and ensuring research has a real impact. Regular updating of such maps will help to maintain a global overview of gaps and tell us how well the violence prevention field is doing to strengthen evidence-informed strategies," said corresponding author Ramya Subrahmanian, PhD, of UNICEF-Innocenti.

Credit: 
Wiley

Oncotarget: Sirolimus-eluting stents -- opposite in vitro effects on the clonogenic cell potential

image: Experiment design for clonal assay in T75 flasks in cell lines treated with sirolimus at different time and concentration. Experiments parameters used were: - synchronized colonies, no use of CO2, fructose based media, - antibiotics free (streptomycin/penicillin) - long term exposition to sirolimus (5 weeks) - cells are grown for 1 months before any treatment - doubling time was constant for cell lines so growth of cells is predictable - monodisperse of cells

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Correspondence to - Gianandrea Pasquinelli - gianandr.pasquinelli@unibo.it

The cover for issue 31 of Oncotarget features Figure 4, "Concentration dose-response curves of sirolimus effect [55 nM–1 nM] on the number of cells per surviving colony in U2OS cell line after 2 weeks exposure," by Vasuri, et al. which reported that the authors evaluated the long-term effects of sirolimus on three different cell in vitro models, cultured in physiological conditions mimicking sirolimus-eluted stent, in order to clarify the effectiveness of sirolimus in blocking cell proliferation and survival.

Three cell lines were selected and growth in 10 ml of Minimum Essential Medium for 5 weeks with serial dilutions of sirolimus.

The number of colonies and the number of cells per colony were counted.

As a result, the number of WPMY-1 surviving colonies increased in a dose-dependent manner when treated with sirolimus, while the number of U2OS colonies progressively decreased.

In conclusion sirolimus showed the well-known cytostatic effect, but with an effect on clonogenic potential different among the different cell types.

Dr. Gianandrea Pasquinelli from The Bologna University said, "Rapamycin (sirolimus) is a widely used cytostatic drug blocking the cell cycle in the phase G1/S through the inhibition of the mammalian target of Rapamycin (mTOR) pathway, that has found several clinical applications, from immunosuppression in diabetes and organ transplantation to cancer therapy and drug-eluting stents (DES)"

Beside to its cytostatic activity, sirolimus was also discovered to protect normal human oral keratinocytes from apoptosis by activating autophagy, and to act as a basal stem cell keratinocyte-protecting drug in irradiated mice.

The effect of sirolimus on mesenchymal cells is unknown, but it is an important issue, since mesenchymal cells such as myofibroblasts and cells promoting vascular calcification play an important role in atherogenesis and vascular restenosis.

Sirolimus seems to block the proliferation and the migration of vascular smooth muscle cells, but we lack information concerning the effects on other cells composing atherosclerotic plaques.

The aim of the present paper is to evaluate the long-term effects of sirolimus, rather than short-term cell survival, on three different cell in vitro models, cultured in Minimum Essential Medium, which simulates physiological conditions (w/o CO2 and glucose, in order to clarify the effectiveness of sirolimus in blocking cell proliferation and survival.

The Pasquinelli Research Team concluded in their Oncotarget Research Paper that the plaque typology and the different cell composition of the plaque, e. g., the presence of inflammatory cells, angiogenesis, prevalence of fibrosis, presence of osteogenic progenitors, may influence the response to sirolimus.

"The presence of inflammatory cells, angiogenesis, prevalence of fibrosis, presence of osteogenic progenitors, may influence the response to sirolimus"

Moreover, it is known that the clonal capacity varies between cells and we should consider this matter when evaluating the effectiveness of eluted stent.

Finally, additional mechanisms can have a role, such as amitotic cell division.

These mechanisms were also observed in human atherogenesis and could be fundamental to evaluate the in vivo effect of sirolimus too.

Credit: 
Impact Journals LLC

Conversation about suicide prevention leads to safe gun storage

image: Forefront Suicide Prevention volunteers talk with visitors to the Safer Night Out community event in Walla Walla, Wash., in August 2019.

Image: 
Forefront Suicide Prevention/University of Washington

Talking to people at gun shows about suicide prevention and the risks of unsecured firearms can lead to safe weapons storage, according to a new study.

The research by Forefront Suicide Prevention at the University of Washington, from visits to 18 gun shows and other community events around Washington state last year, found that engaging people in a community-based setting, in an empathetic conversation focused on safety, resulted in more people locking up their firearms.

The results are promising, lead author and Forefront co-founder Jennifer Stuber said, because they show that meeting people where they're at, physically and psychologically, can lead to behavior change that can prevent tragedy.

"We need to be educating people who own firearms or are considering purchasing them that suicide is a possible risk to take into consideration and to make plans in advance to mitigate these risks. So many people are in crisis today -- from youth, to veterans, to our men in economic distress and in relationship turmoil -- we are all vulnerable. We need to educate firearms owners, both experienced and new, at the point of purchase and other places we can find them to raise awareness," said Stuber, an associate professor of social work at the UW.

The study published Oct. 20 in BMJ Injury Prevention.

According to national and state data, about half of all suicides involve firearms. In Washington state, three-quarters of all firearm fatalities are suicides, which most people aren't aware of when they purchase a firearm, Stuber said. Suicide rates are higher among men than women, and higher among veterans than nonveterans. A 2019 Forefront study focused on the potential role of firearms retailers in preventing suicides, by evaluating store owners' willingness to learn about the issue and train their employees in how to spot and act on suicide warning signs. That study found that many retailers were interested in learning more and adopting prevention strategies among their staff.

The new study tested an outreach strategy created by Forefront known as SAFER, an extension of its multi-faceted Safer Homes, Suicide Aware program, which offers training, education and locking devices for firearms and medications in communities across Washington.

Forefront's trained staff and volunteers regularly provide suicide-prevention trainings tailored to students, teachers, parents, veterans, health care workers and pharmacists. In reaching out to visitors to gun shows -- who are mostly men, often veterans -- Forefront designed the brief, motivational interviewing approach it calls SAFER (Signpost, Assess, Facts, Emotion and Recommend) to both educate and listen with empathy. By talking with a person about their familiarity with issues surrounding suicide and their understanding of the risks of unsecured firearms, the volunteer can deliver a suicide-prevention recommendation that encourages safe firearms storage. The volunteer also provides the person with a free locking device for hand-guns, rifles or AR-15s to take home.

In this study, 1,175 people received the SAFER intervention. They took a short, written survey to assess knowledge of firearms safety and suicide prevention prior to the SAFER conversation. Most SAFER encounters took about 10 to 20 minutes each.

Four weeks later, Forefront emailed a survey to people who received the intervention. Of the 372 who completed the survey, 66% said they now kept their firearms secure at home, a 15 percentage-point increase from the 51% who reported doing so during the pre-intervention survey.

"To my knowledge, this is the first study to assess receptiveness to suicide prevention messages and self-reported change in firearm storage behavior at gun shows," said Ali Rowhani-Rahbar, an associate professor of epidemiology and co-director of the Firearm Injury and Policy Research Program at the UW. Prior studies had focused on clinical or other community settings, including those in Washington state. "This study is novel not only due to its outreach to participants in gun shows, but also because of its empathetic approach to engage them in conversations about suicide prevention. It can serve as a model for other regions of the country to use similar approaches and broaden the inclusion of individuals who might be at high risk of suicide in their outreach and prevention programs."

Initially, people may not think suicide-prevention awareness applies to them, Stuber said. But that's a key message of the intervention: Life circumstances can and do change. Even if you never have thoughts of suicide, it's critical to have a plan to protect yourself, your family, even friends or strangers who visit your home by locking up firearms and medications and understanding what to do if you are someone you care about is at risk.

"We're building on the idea that people want to do the right thing here, but they don't necessarily know what the right thing is," Stuber said.

As part of the SAFER intervention, volunteers also offered a locking device for medications. In the pre-intervention survey, 15% of participants said they safely stored medications -- a proportion that grew to about 22% afterward, according to the study. Even a modest increase shows a positive impact, Stuber noted, and provides important information for enhancing the strategy going forward. Currently, the emphasis is on locking up firearms, which is the main goal for the audience and the setting.

Forefront continues to improve SAFER to hone in on the demographics of the person receiving the intervention and to tailor the message accordingly, Stuber said. For example, if the individual has children, the volunteer can focus on the risks of a child gaining access to a firearm and emphasizing the need for a fast-access firearm locking device, which participants also receive education about through a raffle at gun shows.

Another key is to expect emotion, Stuber added. People routinely shared personal experiences with suicide or concerns about friends or relatives, which could end up being an opportunity to counsel or provide resources beyond the individual receiving the SAFER intervention.

"We don't want to firehose people with facts and statistics. We should be listening more than talking," Stuber said.

During the COVID-19 pandemic, Forefront has begun offering a "tele-SAFER" intervention, as well, through individualized Zoom sessions facilitated by veterans organizations and nonprofit groups, Stuber said.

Credit: 
University of Washington

Cannabis reduces OCD symptoms by half in the short-term

PULLMAN, Wash. - People with obsessive-compulsive disorder, or OCD, report that the severity of their symptoms was reduced by about half within four hours of smoking cannabis, according to a Washington State University study.

The researchers analyzed data inputted into the Strainprint app by people who self-identified as having OCD, a condition characterized by intrusive, persistent thoughts and repetitive behaviors such as compulsively checking if a door is locked. After smoking cannabis, users with OCD reported it reduced their compulsions by 60%, intrusions, or unwanted thoughts, by 49% and anxiety by 52%.

The study, recently published in the Journal of Affective Disorders, also found that higher doses and cannabis with higher concentrations of CBD, or cannabidiol, were associated with larger reductions in compulsions.

"The results overall indicate that cannabis may have some beneficial short-term but not really long-term effects on obsessive-compulsive disorder," said Carrie Cuttler, the study's corresponding author and WSU assistant professor of psychology. "To me, the CBD findings are really promising because it is not intoxicating. This is an area of research that would really benefit from clinical trials looking at changes in compulsions, intrusions and anxiety with pure CBD."

The WSU study drew from data of more than 1,800 cannabis sessions that 87 individuals logged into the Strainprint app over 31 months. The long time period allowed the researchers to assess whether users developed tolerance to cannabis, but those effects were mixed. As people continued to use cannabis, the associated reductions in intrusions became slightly smaller suggesting they were building tolerance, but the relationship between cannabis and reductions in compulsions and anxiety remained fairly constant.

Traditional treatments for obsessive-compulsive disorder include exposure and response prevention therapy where people's irrational thoughts around their behaviors are directly challenged, and prescribing antidepressants called serotonin reuptake inhibitors to reduce symptoms. While these treatments have positive effects for many patients, they do not cure the disorder nor do they work well for every person with OCD.

"We're trying to build knowledge about the relationship of cannabis use and OCD because it's an area that is really understudied," said Dakota Mauzay, a doctoral student in Cuttler's lab and first author on the paper.

Aside from their own research, the researchers found only one other human study on the topic: a small clinical trial with 12 participants that revealed that there were reductions in OCD symptoms after cannabis use, but these were not much larger than the reductions associated with the placebo.

The WSU researchers noted that one of the limitations of their study was the inability to use a placebo control and an "expectancy effect" may play a role in the results, meaning when people expect to feel better from something they generally do. The data was also from a self-selected sample of cannabis users, and there was variability in the results which means that not everyone experienced the same reductions in symptoms after using cannabis.

However, Cuttler said this analysis of user-provided information via the Strainprint app was especially valuable because it provides a large data set and the participants were using market cannabis in their home environment, as opposed to federally grown cannabis in a lab which may affect their responses. Strainprint's app is intended to help users determine which types of cannabis work the best for them, but the company provided the WSU researchers free access to users' anonymized data for research purposes.

Cuttler said this study points out that further research, particularly clinical trials on the cannabis constituent CBD, may reveal a therapeutic potential for people with OCD.

This is the fourth study Cuttler and her colleagues have conducted examining the effects of cannabis on various mental health conditions using the data provided by the app created by the Canadian company Strainprint. Others include studies on how cannabis impacts PTSD symptoms, reduces headache pain, and affects emotional well-being.

Credit: 
Washington State University

Kitchen temperature supercurrents from stacked 2D materials

image: Excitons form across layers in a 3D superlattice of stacked 2D semiconductors

Image: 
Olivia Kong

Could a stack of 2D materials allow for supercurrents at ground-breakingly warm temperatures, easily achievable in the household kitchen?

An international study published in August opens a new route to high-temperature supercurrents at temperatures as 'warm' as inside a kitchen fridge.

The ultimate aim is to achieve superconductivity (ie, electrical current without any energy loss to resistance) at a reasonable temperature.

TOWARDS ROOM-TEMPERATURE SUPERCONDUCTIVITY

Previously, superconductivity has only been possible at impractically low temperatures, less than -170°C below zero - even the Antarctic would be far too warm!

For this reason, the cooling costs of superconductors have been high, requiring expensive and energy-intensive cooling systems.

Superconductivity at everyday temperatures is the ultimate goal of researchers in the field.

This new semiconductor superlattice device could form the basis of a radically new class of ultra-low energy electronics with vastly lower energy consumption per computation than conventional, silicon-based (CMOS) electronics.

Such electronics, based on new types of conduction in which solid-state transistors switch between zero and one (ie, binary switching) without resistance at room temperature, is the aim of the FLEET Centre of Excellence.

EXCITON SUPERCURRENTS IN ENERGY-EFFICIENT ELECTRONICS

Because oppositely-charged electrons and holes in semiconductors are strongly attracted to each other electrically, they can form tightly-bound pairs. These composite particles are called excitons, and they open up new paths towards conduction without resistance at room temperature.

Excitons can in principle form a quantum, 'superfluid' state, in which they move together without resistance. With such tightly bound excitons, the superfluidity should exist at high temperatures--even as high as room temperature.

But unfortunately, because the electron and hole are so close together, in practice excitons have extremely short lifetimes--just a few nanoseconds, not enough time to form a superfluid.

As a workaround, the electron and hole can be kept completely apart in two, separated atomically-thin conducting layers, creating so-called 'spatially indirect' excitons. The electrons and holes move along separate but very close conducting layers. This makes the excitons long-lived, and indeed superfluidity has recently been observed in such systems.

Counterflow in the exciton superfluid, in which the oppositely charged electrons and holes move together in their separate layers, allows so-called 'supercurrents' (dissipationless electrical currents) to flow with zero resistance and zero wasted energy. As such, it is clearly an exciting prospect for future, ultra-low-energy electronics.

STACKED LAYERS OVERCOME 2D LIMITATIONS

Sara Conti who is a co-author on the study, notes another problem however: atomically-thin conducting layers are two-dimensional, and in 2D systems there are rigid topological quantum restrictions discovered by David Thouless and Michael Kosterlitz (2016 Nobel prize), that eliminate the superfluidity at very low temperatures, above about -170°C.

The key difference with the new proposed system of stacked atomically-thin layers of transition metal dichalcogenide (TMD) semiconducting materials, is that it is three dimensional.

The topological limitations of 2D are overcome by using this 3D `superlattice' of thin layers. Alternate layers are doped with excess electrons (n-doped) and excess holes (p-doped) and these form the 3D excitons.

The study predicts exciton supercurrents will flow in this system at temperatures as warm as -3°C.

David Neilson, who has worked for many years on exciton superfluidity and 2D systems, says "The proposed 3D superlattice breaks out from the topological limitations of 2D systems, allowing for supercurrents at -3°C. Because the electrons and holes are so strongly coupled, further design improvements should carry this right up to room temperature."

"Amazingly, it is becoming routine today to produce stacks of these atomically-thin layers, lining them up atomically, and holding them together with the weak van der Waals atomic attraction," explains Prof Neilson. "And while our new study is a theoretical proposal, it is carefully designed to be feasible with present technology."

Credit: 
ARC Centre of Excellence in Future Low-Energy Electronics Technologies

The consequences of mating at the molecular level

image: Researchers from the University of Tsukuba identified a novel mechanism by which mating affects the behavior of germline stem cells (GSCs). By studying Drosophila melanogaster, the researchers showed that the neurons that are activated during mating result in increased intracellular calcium signaling in cells adjacent to GSCs, which in turn resulted in the activation of the protein matrix metalloproteinase to increase GSCs. This study describes how stem cell behavior is regulated by environmental cues.

Image: 
Photo by Yuto Yoshinari; University of Tsukuba

Tsukuba, Japan - While it is known that stem cells have the ability to develop into all tissues in a precisely regulated process, the way environmental cues affect stem cell behavior has remained poorly understood. In a new study, researchers from the University of Tsukuba discovered that neurons producing the neurotransmitter octopamine regulate the behavior of germline stem cells (GSCs) in response to environmental cues, such as mating.

The ovaries of the fruit fly Drosophila melanogaster have been a robust model system for studying the relationship between environmental cues and stem cell biology. In fruit flies, GSCs give rise to eggs and exist in close proximity to somatic cells. Somatic cells comprise several types of cells in support of the budding eggs. As with other stem cells, when GSCs divide, one daughter cell retains its stem cell identity, while the other differentiates into multiple progeny cells. The balance between self-renewal and differentiation is tightly regulated, both by cues within and outside the environment in which GSCs reside (also called a niche). Mating is one such external cue known to increase GSCs.

"It is well known that a molecule called sex peptide from the male seminal fluid activates neurons located in the uterine lumen. We have previously shown that these neurons are essential for stimulating the biosynthesis of ovarian steroid hormones to increase the number of GSCs," says corresponding author of the study Professor Ryusuke Niwa. "The goal of our study was to investigate how the information from mating is transmitted from these neurons to GSCs at the molecular and cellular levels."

To achieve their goal, the researchers took a genetic approach to investigate which gene is responsible for the increase of GSCs upon mating, and found that the octopamine receptor Oamb is the one through which octopamine exerts its effect on GSCs. Through a series of experiments, the researchers then found that Oamb in escort cells, one type of somatic cell adjacent to GSCs, modulates GSC increase after mating and the subsequent release of octopamine by neurons. At the molecular level, Oamb activation by octopamine resulted in an increase in calcium signaling in escort cells. Calcium is a potent biomolecule and changes in cellular calcium levels strongly affect cell behavior.

Because it had previously been shown that ovarian steroid hormones were involved in the increase of GSCs, the researchers next investigated the relationship between ovarian steroid hormones and the calcium-dependent GSC increase. Their results showed that ovarian steroid hormones are indeed required to increase the number of GSCs. Next, the researchers asked which molecules play a role in stimulation of escort cells by octopamine and found that the protein matrix metalloproteinase 2 is required upon the calcium-dependent GSC increase. Finally, the researchers showed that the neurons projecting to the ovaries to increase GSCs do so via specialized proteins, called nicotinic acetylcholine receptors. These results provide a complete picture as to how neuronal activation results in increased ovarian stem cells.

"These are striking results that show the molecular mechanism underlying the coupling of the nervous system with stem cell behavior in response to environmental cues, such as mating," says Professor Niwa. "Our results could help unravel the conserved systemic and neuronal regulatory mechanisms for stem cell homeostasis in animals."

Credit: 
University of Tsukuba

More research needed to determine safety of hip and knee steroid injections

(Boston)-- Although frequently used to treat painful osteoarthritis of the hip and knee, intra-articular corticosteroid (IACS) injections remain controversial. Questions about whether damage to joints occurs as a result of these injections, which are performed thousands a time each day, persist.

Osteoarthritis of the hip and knee is among the most common joint disorders. A frequently performed treatment for osteoarthritis and other joint related pain syndromes are IACS, yet there is conflicting evidence on their potential benefit and possible negative outcomes following such injections.

"As of today, there is no established recommendation or consensus regarding imaging, clinical,
or laboratory markers before an IACS injection is performed to screen for osteoarthritis-related imaging abnormalities and repeating radiographs before each subsequent IACS injection to detect possible adverse joint findings remains controversial," explains corresponding author Ali Guermazi, MD, PhD, chief of radiology at VA Boston Healthcare System and professor of radiology at Boston University School of Medicine (BUSM).

Guermazi and his colleagues had first reported that accelerated arthritis and joint destruction are observed in some patients who received intra-articular corticosteroid injections. (Radiology/2019) https://pubs.rsna.org/doi/10.1148/radiol.2019190341

In this new study, Guermazi led an international expert panel of researchers who reviewed all published evidence in the literature and found not enough evidence exists to decisively draw a conclusion. However, they did recommend the use of imaging for first time injections or multiple injections with the aim of mitigating the risk for joint collapse and total joint replacement. In addition, the panel reviewed the current understanding of pain in osteoarthritis and summarized current international guidelines regarding indications for IACS injection. They also suggested profiles of those who would likely benefit most from IACS injection and recommended updating patient consent forms until further evidence on the topic is available.

The researchers hope that studies with mid- to long-term follow-up will soon be available and provide data from before and after IACS injection compared to appropriate controls. "Understanding the real benefit of IACS in relieving joint pain is paramount," added Guermazi.

These findings appear online in the journal Radiology.

Credit: 
Boston University School of Medicine

COVID-19 cough clouds in closed spaces

image: Volume of cough cloud generated by a human subject increases with time due to entrainment of the surrounding air into it (Bottom). Change in volume of the cloud as a function of distance from mouth (Top). Masks reduce the volume significantly as seen in the inset.

Image: 
Amit Agrawal and Rajneesh Bhardwaj

WASHINGTON, October 20, 2020 -- As the coronavirus has affected more than 30 million people globally, researchers have increasingly focused on the extent to which airborne respiratory droplets carrying the virus travel and contaminate the air after an infected person coughs.

While scientists have studied the properties of air at the mouth, such as volume, temperature, droplet distribution, and humidity, less is known about how these properties change as the cough cloud travels. In Physics of Fluids, by AIP Publishing, researchers estimate the evolving volume of the cough cloud and quantify the reduction in its volume in the presence of a face mask.

"We estimate this volume of the air, which may help to design ventilation of closed spaces and consequently reduce the spread of the disease," said Amit Agrawal, one of the authors.

The researchers also examined the variation in temperature and humidity in the cough cloud as the determinant that impacts the droplet distribution in the cloud.

Using an analysis based on jet theory and experimental data from the literature, they found that it's the first 5 to 8 seconds after coughing that matter for suspending the exhaled droplets in the air and, consequently, for the spread of the disease. After that time, the cough cloud typically starts to disperse.

The scientists found the cloud volume without a mask is about 7 times larger than with a surgical mask and 23 times larger than with an N95 mask.

"We found that anything that reduces the distance traveled by the cloud, such as a mask, handkerchief, or coughing into an elbow, should greatly reduce the region over which the droplets disperse upon coughing and therefore the chances of infection," said Rajneesh Bhardwaj, another author.

Interestingly, the researchers found how hard a person coughs, which impacts the initial velocity and volume of coughing, does not affect the volume in the cough cloud when the person is not wearing a mask, although the initial volume is very important for a person wearing a mask.

The scientists determined the volume of a cough cloud varies as a cube of the total distance traveled by the cloud with the proportionality constant being 1 to 150. This formula will be helpful in determining the maximum number of people that can be accommodated in a hospital ward, and the minimum rate at which air in a room, elevator, cinema hall, car, aircraft cabin, or restaurant needs to be circulated to maintain freshness and reduce the chance of infection.

Credit: 
American Institute of Physics

Study finds lowering nicotine decreases addictiveness of smoking in vulnerable populations

image: A sample package of unlabeled study cigarettes used by researchers at the University of Vermont, Brown University and Johns Hopkins University. Study cigarettes included three different nicotine content categories: very-low nicotine, moderately-low, or control-dose (comparable to store-bought).

Image: 
Vermont Center on Behavior and Health, University of Vermont

More than 480,000 U.S. deaths per year, as well as diseases affecting 16 million living Americans, can be attributed to cigarette smoking, according to the Centers for Disease Control and Prevention. In particular, this behavior continues to be overrepresented among those with mental illness, substance use disorders, and socioeconomic disadvantage.

An October 20 study in JAMA Network Open provides evidence that, even in smokers from vulnerable populations, reducing nicotine content to low levels decreases addictiveness - a timely finding as the Food and Drug Administration (FDA) considers a policy to lower nicotine content in all cigarettes sold in the U.S.

Led by Stephen T. Higgins, Ph.D., director of the Vermont Center on Behavior and Health at the University of Vermont's (UVM) Larner College of Medicine, in collaboration with colleagues at Brown University and Johns Hopkins University, the study sought to determine if reducing the nicotine content of cigarettes decreases smoking rates and nicotine dependence severity among adults with psychiatric disorders or socioeconomic disadvantage.

Three double-blind, randomized clinical trials were conducted at UVM, Brown, and Johns Hopkins between October 2016 and September 2019, with data analyzed from September 2019 to July 2020. A total of 775 daily smokers with affective disorders, opioid use disorder, or socioeconomic disadvantage who were NOT currently trying to quit smoking were deemed eligible.

Participants were randomly assigned to use research cigarettes for 12 weeks that contained either 0.4 mg nicotine/g tobacco, 2.4 mg nicotine/g tobacco (both known as very low-nicotine content cigarettes or VLNCs), or 15.8 mg nicotine/g tobacco (a level comparable to a standard commercial cigarette). NIH provided the study cigarettes, and all were identical in appearance. Assignment to the two VLNCs decreased daily smoking rate by an average of roughly 30 percent, as well as nicotine dependence severity and biochemical measures of smoke exposure compared to those using the cigarettes with nicotine content at levels in commercial cigarettes.

"We know that lower smoking rate and dependence severity are two important predictors of successful smoking cessation should someone attempt to quit," said Higgins, who is presenting these latest findings to a conference of tobacco researchers and NIH-FDA officials on October 20, 2020. "Our findings in this and earlier studies suggest that lowering the nicotine content in all cigarettes to minimally addictive levels would benefit all smokers, including those most vulnerable to smoking and addiction."

Credit: 
Larner College of Medicine at the University of Vermont