Culture

Various types of DNA damage can have serious repercussions, both for the individual cells in which
they occur and for the organism as a whole. Instances of simultaneous breakage of both strands of
the DNA helix are particularly harmful. Such double-strand breaks (DSBs) can be induced by
radiation, as well as by environmental toxins, and can lead to cell death. However, cells possess
efficient mechanisms for detecting and repairing DSBs. A molecular machine known as the MR
complex plays a central role in this process. It recognizes and binds to DSBs, and initiates repair of the
broken double helix. A team of scientists led by Professor Karl-Peter Hopfner, who holds the Chair of
Structural Molecular Biology at LMU's Gene Center, has now deciphered the complete three-
dimensional structure of the MR complex and determined how it works. The findings appear in the
journal Molecular Cell.

Hopfner's group had previously shown that the MR complex is made up of four proteins. Two of
these are nucleases, which themselves cut DNA strands. The others are ATPases - enzymes that
remove a phosphate group from the molecule ATP, and in so doing release chemical energy. The
complex itself has an open architecture. But when it encounters a DSB, it binds to the DNA and brings
the ends together, acting as the molecular equivalent of a hook-and-loop fastener. The complex then
detaches any chemical adducts that block the ends of the break and removes further subunits from
the DNA. These operations then provide a 'clean break' in preparation for the repair process itself.
"Because of the intricate architecture of the complex, the conformational changes involved in this
process had not been elucidated," says Lisa Käshammer, lead author of the paper. The ATPase
enzymes contain prominent filamentous structural elements that are referred to as coiled-coils,
which are made up of closely apposed and helically ordered amino-acid sequences. These filaments
are long and flexible, and their mobility had made it impossible to discern their precise courses using
conventional X-ray crystallographic methods.

The team turned to cryo-electron microscopy to get around this problem, and succeeded in
determining the complete structure of the MR complex found in the bacterium Escherichia coli. The
bacterial complex is somewhat less complicated than its counterpart in higher organisms, but in their
overall structure the two forms are similar to each other. The new structure now makes it possible to
discern how the nucleases actually bind to the DNA - a question that had remained open up to now.
"In the previously published structures, the DNA was either positioned relatively far from the active
center of the nuclease, or bound in such a way that the active center was inaccessible," Käshammer
explains. The new structure reveals that binding to the DNA causes the nuclease to execute a 120-
degree turn, which opens up a channel that enables the DNA to bind to the active center of the
enzyme.

The study also clarifies the function of the coiled-coil regions. As the new structural model
demonstrates, these segments form a brace that stabilizes the DNA, and are actively involved in the
binding and processing of the DNA ends. "Our findings constitute an important advance in the quest for a deeper understanding of the complex mechanisms that make it possible for these enzymes to repair double-strand breaks in DNA," says Hopfner. New insights into the function of the complex are
also of potential medical significance, as DSBs play a significant role in the pathogenesis of many
types of cancer.

As the central mediators of cell function in biological organisms, proteins are involved in the execution of virtually all cellular processes. They provide the internal scaffolding that gives cells their form, and enable cells to dynamically alter their morphology. They transport substrates back and forth across membranes, and they catalyze most of the chemical reactions that take place in cells. In the course of these tasks many proteins are subjected to external forces. Indeed, some "mechanosensitive" proteins effectively measure the strength of the forces acting upon them and are activated when the imposed force exceeds a given threshold value. Von Willebrand Factor (VWF), which initiates the formation of blood clots, is an important representative of this class.

The mechanical forces required to activate proteins like VWF are often so small that their magnitude could not be determined using existing methods. Now, a team of scientists led by LMU physicists Martin Benoit and Professor Jan Lipfert has developed a much more sensitive procedure. Their 'magnetic tweezers' can quantify forces that are 100 times smaller than the commonly used alternative method currently available. As Lipfert and colleagues report in the journal PNAS, they have employed the technique to observe the unfolding of the VWF protein under the influence of low mechanical forces.

A powerful approach to study mechanoregulation is so-called protein force spectroscopy. This involves tugging on an individual protein molecule and observing how an applied force alters its three-dimensional structure. Up to now, the method of choice for pulling has been an atomic force microscope, which works best in the range of 100 piconewton (pN). "However, many molecular processes are activated by forces that are much weaker than that," says Lipfert. "So for measurements at the level of single molecules, we need more sensitive instrumentation - there's little point in using a bathroom scale to weigh out the ingredients of a cake."

The researchers developed a method in which the proteins are attached at one end to a glass surface and carry a tag at the other end that binds to tiny magnetic beads and the assembly is then subjected to an externa magnetic field. Extension of the protein induced by the field results in the vertical displacement of each bead, which can be detected by microscopy. "This sort of set-up is referred to as magnetic tweezers," Lipfert explains. "It has the great advantage that it allows us to apply and resolve very weak forces - significantly less than 1 piconewton - to the protein of interest. In addition, magnetic tweezers enable very stable measurements over long periods of time - up to one week!"

To test the new method, the LMU group used VWF as their target protein. In the bloodstream, VWF circulates as a multimer of dimers that are made of two identical subunits. Under normal conditions of blood flow, it has a relatively compact globular form. However, any increase in the shear forces in the bloodstream owing to injury of the vasculature causes vWF to unfold. This exposes binding sites for receptors on blood platelets. Binding of VWF to platelets in turn triggers a reaction cascade that leads to clotting, which seals the wound. "The cascade is induced by the action on the molecule of mechanical forces acting that are much weaker than those that have been measured up to now," says Lipfert. Analysis of the unzipping of VWF dimers with magnetic tweezers showed that the so-called VWF stem opens up under an applied force of less than 1 pN, when the subunits of the dimer are pulled apart like the two halves of a zipper. "We assume that this pattern of behavior, which we were able to observe for the first time, represents the first step in blood coagulation," says Lipfert. "Our approach provides a detailed picture of the forces and the changes in extension involved in unfolding the protein. We are confident that future application of the method will contribute to a better understanding of the mode of action of VWF and of the role of clinically relevant mutations."

A new study provides an updated picture of the prevalence of the sheep and goat plague virus (PPRV), a widespread and often fatal disease that threatens 80 percent of the world's sheep and goats, in northern Tanzania.

According to the research team, livestock managed in a system where they are the sole source of an owners' livelihood are more likely to become infected with PPRV than livestock managed in a system where the owners' livelihood is supplemented by agriculture. Additionally, the presence of cattle may affect infection risk, even though they are not typically considered important hosts for the virus.

The new study, by researchers at Penn State, the University of Glasgow, and the Nelson Mandela African Institute of Science and Technology, appears online in the journal Epidemiology and Infection.

"About 330 million people worldwide rely on sheep and goats for their livelihood, so understanding how major livestock diseases spread is critical," said Catherine Herzog, epidemiologist, current graduate student at Penn State, and first author of the paper. "Peste des petits ruminants virus (PPRV), also known as sheep and goat plague virus, has been reported in over 70 countries in Asia, the Middle East, and Africa, threatening about 80 percent of the world's population of sheep and goats. In this study, we provide an up-to-date look at the prevalence of PPRV in northern Tanzania and explore factors that affect how the disease is transmitted."

PPRV typically kills 50 to 80 percent of the sheep and goats it infects. Those that survive contain antibodies in their blood that recognize the virus and prevent future infection. These antibodies are used by researchers as an indicator of past infection.

The researchers surveyed livestock across villages in northern Tanzania for evidence of past infection, comparing rates in herds from pastoral villages, where people rely almost solely on livestock, and from agropastoral villages, where people rely on a mix of livestock and agriculture.

"According to our models, herds from pastoral villages had 3.8 times the risk of becoming infected and developing detectable antibodies compared to those from agropastoral villages," said Herzog. "If you look only at a herds of sheep or only at herds of goats instead of mixed-species herds, that risk increases to 9.4 or 9.5 times higher, respectively, for pastoral systems when compared to agropastoral systems."

Female sheep and goats also had 1.5 times higher risk of becoming infected than males. Understanding prevalence and infection risk could improve the researcher's ability to predict how the disease will spread and to refine management techniques to minimize disease risk.

"Next we plan to investigate which aspects of the livestock management system within a pastoral herd may be driving this increased risk," said co-author Ottar Bjørnstad, Distinguished Professor of Entomology and Biology and J. Lloyd and Dorothy Foehr Huck Chair of Epidemiology at Penn State, who led the research team. "For example, herd size, herd age structure, contact rates among livestock and wildlife, and access to veterinary service may all play a role in infection risk. Knowing which animals are at greater risk of infection may affect how we allocate resources to manage prevention strategies."

Although PPRV is generally considered to be a sheep and goat virus, the research team also considered cattle in their surveys and analysis.

"Cattle are often managed alongside sheep and goats and can become infected, although it is unclear if cattle can transmit the disease," said Herzog. "We found that the rate at which animals become infected--force of infection--was related between sheep and cattle and between goats and cattle. This is consistent with the idea that cattle play a role in transmission to sheep and goats, or, alternatively, that an unknown external factor is affecting transmission in each species in a similar way."

"To further explore the role of cattle in transmission, we plan to perform experimental transmission trials with all three species with our collaborators in Ethiopia, who also work with us on bovine tuberculosis projects," said co-author Vivek Kapur, Associate Director for Strategic Initiatives at the Huck Institute of the Life Sciences, Huck Distinguished Chair in Global Health, and Professor of Microbiology and Infectious Disease at Penn State. "Understanding if cattle can transmit to sheep or goats ahead of the upcoming global eradication campaign is a top priority."

PPRV is considered an attractive target for eradication due to its socio-economic importance and the availability of a vaccine, which provides protection for sheep and goats from the disease for up to 3 years.

"PPRV is not too unlike rinderpest in cattle--one of only two viruses that we have completely eradicated from the planet, thanks in part to good vaccines," said co-author Peter Hudson, Willaman Professor of Biology at Penn State. "But sheep and goats live shorter lives than cattle, and there are more of them, so it can be a challenge for herd owners to keep up with vaccination. We hope our work will clarify the ecological mechanisms driving PPRV transmission, allowing us to improve vaccination accessibility for at-risk herds and optimize other prevention strategies."

CLEVELAND, Ohio (Sept 4, 2019)--Undergoing a hysterectomy, especially in conjunction with removal of the ovaries, can take a major toll on a woman's mental health. A new study, however, turns the tables on this relationship and investigates the psychiatric symptoms that may prompt a woman to undergo an oophorectomy, even after confirmation of a nonmalignant diagnosis. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

Although multiple studies have previously been conducted to investigate the effects of hysterectomy with or without concurrent bilateral oophorectomy on mental health outcomes, this new study out of the Mayo Clinic is the first to identify psychiatric conditions before a bilateral oophorectomy. The Mayo Clinic's efforts in this area date back to 2016 when it reported study results that showed a higher frequency of depression, anxiety, and substance abuse occurring before the date of bilateral oophorectomy compared with controls. In 2017, the Mayo Clinic additionally reported an association between adverse childhood or adult experiences and the risk of bilateral oophorectomy.

In this latest study, researchers sought to determine whether various psychiatric symptoms directly or indirectly influence a woman's decision to undergo an oophorectomy, even if there were no threat of malignancy. The researchers identified several psychiatric conditions that were associated with an increased risk of undergoing surgery. These included mood disorders, bipolar disorders, anxiety disorders, schizophrenia, personality disorders, dissociative disorders, and somatoform disorders, among others. Although mood and anxiety disorders were the most frequently cited, somatoform and personality disorders proved to have the greatest association.

Given the increased desire throughout the medical industry to develop more conservative treatment and prevention strategies in the future, the study's researchers believe that these results provide valuable insight regarding the relationship between mental health and gynecologic health and how addressing certain emotional issues could lead to alternative, nonsurgical treatment plans.

Study results appear in the article "Mental health conditions diagnoses before bilateral oophorectomy: a population-based case-control study."

"This study serves as an important reminder that mental health issues are common and can sometimes present with physical symptoms. It is incumbent on primary care providers, including gynecologists, to determine whether mental health conditions are playing a role in gynecologic complaints in order to provide patients with the most appropriate care. We know that there are significant long-term adverse health consequences associated with removing a woman's ovaries before the natural age of menopause, let alone the potential risks of an unnecessary surgical procedure," says Dr. Stephanie Faubion, NAMS medical director.

INDIANAPOLIS - In an editorial in the Journal of General Internal Medicine, Regenstrief Institute research scientist Michael Weiner, MD, MPH highlights shortcomings of electronic health records (EHRs) in living up to their full potential, and suggests ways to use EHRs to work more efficiently and ultimately more effectively for patients.

"When I am reading a patient's EHR, a lot of what I want to know and am seeking is what other healthcare professionals learned when they assessed the patient, and what they thought were the most important findings in terms of diagnosis and treatment," said Dr. Weiner, who is an internist. "What I encounter much too often is that key pieces of the patient's record are in the wrong place or embedded so deeply in the EHR that they are hard to locate or may not even have been documented."

"Currently, there are too many distractions in the EHR, such as descriptions of old, resolved problems that are repeatedly cut and pasted again throughout the record, making it difficult to focus on information that matters. The technical challenges are complex, but we need to redesign EHR platforms so that relevant data are clearly and readily accessible."

In his thought-provoking editorial titled "Forced Inefficiencies of the Electronic Health Record," Dr. Weiner draws upon his experience as a primary care physician to propose 13 specific principles that he believes will improve EHRs to the benefit of both clinicians and the patients for whom they care. He challenges EHR vendors, health systems, doctors, nurses and other front-line professionals to adopt these measures to fight inefficiencies and improve the function of the EHR. Until they do, he believes, EHR systems will continue to be slow, cumbersome, and difficult to use, with vital medical information overshadowed by voluminous unimportant content, distracting healthcare providers and potentially resulting in medical errors. Improvements in EHR design and user interfaces can correct many of their deficiencies.

With many clinicians spending about half of the workday on EHR and desk work, Dr. Weiner's goal is to stop unnecessary repetition and misplacement of information within patient records, squelch user burnout related to information overload and the burdens imposed by many EHR systems, and ultimately to combat the adverse consequences of today's EHR's on patient care.

Many of his recommendations target EHR vendors and their product designs, while others are directed at users and others who work in healthcare settings.

Dr. Weiner, who is both a practicing physician and a health services and outcomes researcher studying doctor-patient and clinician-clinician communication, also observes that when patients have the ability to examine and contribute to their own EHR, there can be a positive effect both on accuracy and patient satisfaction.

He concludes the editorial by speaking out for physicians dedicated to patient care. He writes, "Most of all, when it comes to the record [EHR] and me [the physician interacting with the patient], I still want my voice, that part of the record that tells other people what I think the problem is, and what should be done about it."

WASHINGTON -- The pending deal for Altria to purchase 35% of Juul Labs should serve as a "wake-up call" for the careful monitoring of competition in the nicotine delivery market, and for evaluating how regulations and policies impact cigarette and non-cigarette firms selling alternative nicotine delivery products, says a Georgetown University professor. Juul Labs, the largest US seller of vaping products, would merge with Altria, seller of Marlboro cigarettes and a leading seller of smokeless tobacco.

Writing in BMJ (Open Access), David Levy, PhD, professor of oncology at Georgetown Lombardi Comprehensive Cancer Center, and colleagues explore the motivations of Altria in buying Juul Labs and the motivations as to why Juul would accept the offer.

"While Juul Labs has clear motivations for the deal, Altria's motivations to pay $12.8 billion for a non-controlling stake are less clear," write Levy and his colleagues.

The researchers also explore the future impact of the deal on the US cigarette and alternative nicotine delivery markets and on public health.

"From a public health perspective, the impact of this deal will depend on whether it leads to increased cigarette use, less cigarette use, or an increase of e-cigarette use instead of cigarettes," explains Levy.

Hanover, N.H., September 4, 2019 -- Once in short supply, neonatal intensive care units (NICU) are indispensable life savers for critically ill newborns, typically born premature with very low birth weight. But a new Dartmouth report finds that, following a robust national expansion of NICUs over the last two decades, nearly half of all newborns admitted to U.S. NICUs are of normal birth weight.

At the same time, nearly 15% of very low birth weight babies (less than 1500 grams/3.3 pounds) do not receive care in Level III or IV NICUs, despite evidence showing fewer deaths and complications for these newborns when they receive care in NICUs with the highest capabilities to treat very sick newborns, according to the report.

The Dartmouth Atlas of Neonatal Intensive Care offers the first comprehensive examination of U.S. neonatal care across large populations of newborns, using data from the National Center for Health Statistics of the Centers for Disease Control (CDC), Texas Medicaid, and Anthem Blue Cross Blue Shield commercial and Medicaid plans.

The report raises questions about how medical care is provided to our nation's newborns, particularly to those born premature or with other health problems. "Regardless of the infant population we studied, newborn and NICU care varied markedly across regions and hospitals. Little of the variation was explained by differences in newborn health needs. The care that similar newborns receive is strikingly different in one hospital compared to another," said principal author David C. Goodman, MD, MS, of The Dartmouth Institute for Health Policy & Clinical Practice at the Geisel School of Medicine at Dartmouth.

The supply of neonatal intensive care beds grew 65% from 1995-2013, according to the report. The supply of neonatologists grew even faster, increasing 75% from 1996- 2013. At the same time, the number of newborns has remained relatively stable. This has led to increasing numbers of lower risk newborns being admitted to NICUs.

The study finds that the growth in NICU care has not occurred where it is most needed. Regions of the country with a high proportion of premature newborns, or other factors related to newborn illness, such as maternal education level or the rate of cesarean sections, are not the regions with higher supply of NICU beds or neonatologists.

"We should not spare a dollar in providing the best care for newborns. But spending more doesn't help infants if they could receive the care they need in a maternity unit or home with their mothers." Goodman said. "It is very troubling that such a valuable and expensive health care resource is not distributed where it is needed."

Thirty years ago, the most common newborn admitted to a NICU was of low birth weight. In 2017, normal birthweight babies accounted for 48.0% of NICU admissions.

Very low birth weight newborns who are born in hospitals with higher level NICUs (level III or IV) have lower mortality and fewer serious complications than if born in a hospital without a NICU or a Level II unit. Ensuring that more pregnant women deliver in hospitals with appropriate NICU capabilities is a goal of Health People 2020, our national blueprint for improving the nation's health.

For very sick newborns, the benefits of NICUs clearly outweigh any risks. "But those with less severe illnesses have less to gain from intensive care yet are still exposed to the possible adverse effects of a hospital setting designed primarily for critical care," the report states.

Potential adverse effects include:

Many NICUs are relatively bright and noisy, while newborn sleep patterns and neurodevelopment depend on quiet and dim lights, particularly at night.

Despite the best efforts of doctors and nurses, interactions between the newborn and mother are often affected, impairing maternal-newborn bonding and breastfeeding, and potentially leading to disruptions in newborn development and the risk of depression for mothers.

Hospital-acquired infections and antibiotic use are also more likely, as are more frequent blood and imaging tests.

Similar to any intensive care environment, errors in medication dose, mechanical ventilation, and feeding occur.

Finally, when premature newborns are stable and growing, there are missed opportunities to transfer back to a hospital closer to home.

The report sheds light on growing concerns among some neonatologists about balancing these potential harms against possible benefits for late preterm and mildly ill newborns. "Identifying overuse could reveal opportunities to decrease adverse effects, reduce unnecessary spending, allow for earlier discharge home, and improve outcomes for newborns and their families," the report notes.

The highest variation in regional NICU admission rates was seen in the normal birth weight (? 2,500 grams) newborns. Regions with low admission rates included Richmond, Virginia (1.6% of normal weight babies), Laredo, Texas (1.7%), Valdosta, Georgia (1.7%), Roanoke, Virginia (1.8%), and Corpus Christi, Texas (1.8%). Regions with the highest rates included Newark, Delaware (9.2%), Alexandria, Louisiana (9.0%), El Paso, Texas (8.9%), Stony Brook, New York (8.3%), and Staten Island, New York (8.1%).

The report raises questions about the nation's spending on perinatal care, among them:

Is the NICU boom being driven by medical need or by competition among hospitals for newborns and the high margins they earn when some of those newborns are admitted to NICUs?

Are mildly ill newborns receiving care they need and their families want, or is care induced by the increasing availability of NICU beds?

Higher use of NICU care does not change the nation's fundamental problem of poor newborn outcomes at the time of birth. Have we over invested in NICUs and under invested in women's reproductive health services?

Most NICUs are "high-margin" services for hospitals. A 2013 March of Dimes study reported that hospitalization costs average $54,000 for preterm infants. An article in Managed Care magazine in 2010 reported that NICU care accounts for 75 percent of all dollars spent for newborn care. This is a strong financial incentive for further building and expansion of NICUs and for keeping those beds full, potentially leading to overuse of services, especially in lower-risk newborns.

In Texas, for example, the cost to Medicaid for newborn care in 2014 was $1.1 billion, with newborns requiring special care (i.e., elevated care in either a NICU or a maternal-newborn care unit) accounting for 85% of the total. Most (85%) of the payments were for facility charges (i.e., hospitals), with the balance accounted for by professional services, primarily physician bills.

Preliminary analyses failed to find either benefit or harm in the markedly different NICU length of stay, the report notes. "If confirmed in further studies, there are opportunities to reduce the intensity of care and payments and to increase the value of newborn care across the nation," the report states.

CHAMPAIGN, Ill. -- It's increasingly common for managers to direct employees to "be creative" during office brainstorming sessions. But should employees acquiesce to that managerial edict? According to a new paper from a U. of I. expert in work behaviors and organizations, being creative in the workplace is potentially precarious because creativity itself is deeply personal, which can make the creative act feel self-disclosing.

Research from Jack Goncalo, a professor of business administration at the Gies College of Business, investigates the psychological and interpersonal consequences of creativity, showing that when prompted to be creative, people share ideas that reflect their unique point of view and personal preferences - which can be risky business in the office.

"One of the things organizations often tell their employees is be creative, but that's not a benign instruction," Goncalo said. "When you're being creative, you're sharing something about yourself and allowing others to make judgments about you. I think people - both managers and employees - should be mindful of the risks involved. There ought to be some caution flags raised around the idea that employees can be freely creative, unless you go through a lot of hoops to make sure there aren't consequences."

Whether it's formulating the latest scientific breakthrough, developing new technology or creating a collaborative work of art, creativity not only entails conjuring novel ideas but also mustering the courage to openly express those ideas to colleagues, and thereby expose them to criticism.

"When people are being creative, they're not just solving problems. They're actually revealing something deeply personal," Goncalo said. "The ideas that we share when we're brainstorming and generating ideas - they're not just abstract, cold solutions to a problem. They're derived from our own unique idiosyncratic perspective. You're reaching down into yourself to share something that reflects your point of view, and that makes sharing those ideas risky, personal and consequential."

Over the course of five experiments, Goncalo and co-author Joshua H. Katz, a graduate student at Illinois, sought to test the hypothesis that generating creative ideas would prompt the perception of self-disclosure.

When subjects were told to be creative, they inevitably "thought about their own preferences, their own likes and dislikes, and less about what other people thought," Goncalo said.

"That reveals why creativity is risky, and it reveals something about the process that people go through, and we measure this in the paper," he said. "We had experiments where we instructed people to generate creative ideas for potato chip flavors and candle scents, and you can't help but read their ideas and feel like you know the person afterward."

Most of the research on creativity is on its antecedents and how to generate more of it. But this paper shows that there are consequences to being creative, Goncalo said.

"When you say you don't like my idea, you're actually rejecting someone's perspective or point of view, which is dangerously close to rejecting that person - which is risky, to say the least, when you're in a workplace," he said.

Another finding of the research is that being creative together is a way of getting to know someone else.

"When I hear your creative ideas, I get the sense that I can predict something about your personality," Goncalo said.

One of the respondents for the creative candle scent experiment came up with some fairly unique ideas - "Zombie Outbreak," "Spoiled Milk in a Hot Car" and a euphemism for canine flatulence.

"Based on those ideas, you may feel like you know this person, but you also might not necessarily like them," he said. "When people are being creative, they are sharing the kind of information that may rub people the wrong way."

Being creative also is something that can help people bond or know each other better, Goncalo said.

"The most positive spin on this is that when people are creative together, a byproduct is that they get to know each other a little better," he said. "Then again, you might not like what you hear. That's where the risk comes from, but you can certainly match people on their mutual preferences, which could easily lead to bonding."

The research not only has implications for creative types and marketing managers, but also for any group setting where out-of-the-box thinking and brainstorming is demanded.

"This speaks to making people feel anonymous when they're brainstorming," Goncalo said. "It's the same reason that people share more when they know that their response will be anonymous, because there's less risk. So one way to be more creative is by lowering the risk, but also realizing that it's an opportunity to get to know each other better. It could certainly be an icebreaker."

September 4, 2019 -- Bisexual women had higher rates of past-year and daily marijuana use compared to heterosexual women, according to a study just published at Columbia University Mailman School of Public Health. Gay/lesbian women were also more likely to report daily marijuana use and past year medical marijuana use than heterosexual women. While previous research has explored the association between state-level medical marijuana laws (MMLs) and marijuana use (MU) and MU disorder (MUD) among the general U.S. population, this is the first to explore this relationship for lesbian, gay and bisexual (LGB) individuals, including gender differences. The findings are online in the journal Drug and Alcohol Dependence.

"Our work builds on the Institute of Medicine report highlighting the importance of conducting additional research on LGB populations across the life course," said Morgan Philbin, PhD, assistant professor of Sociomedical Sciences at Columbia's Mailman School. ""While research has explored how LGB discrimination polices may impact substance use, less work has explored how substance use policies may impact LGB men and women differently than heterosexuals."

The researchers analyzed data from 126,463 adults 18 and older in the 2015-2017 National Survey on Drug Use and Health to study the odds of past-year marijuana use, any past-year medical marijuana use, daily/near-daily marijuana use, and marijuana use disorder. They also tested the interaction between residence in a state with medical marijuana laws and sexual identity.

When the researchers examined the relationship between state MML status and MU outcomes they found that gay/lesbian women in MML states had higher daily/near-daily (300+ days/year) MU than gay/lesbian women in non-MML states while bisexual women in MML states had higher past-year use than bisexual women in non-MML states; both lesbian/gay and bisexual women in MML states had higher medical MU than those in non-MML states.

"We further extended these findings to estimate daily/near-daily MU prevalence, which was seven times higher among bisexual women than heterosexual women and 2.3 times as high for bisexual men compared to heterosexual men," noted Silvia Martins, MD, PhD, associate professor of Epidemiology and senior author.

Past-year marijuana use was 10 percent among heterosexual women, 26 percent among gay/lesbian women and 40 percent among bisexual women. Daily use was lower among heterosexual women (1.5 percent) compared to lesbians (6 percent) and bisexual women (10 percent). Similar patterns emerged for past-year marijuana use disorder.

Past-year marijuana use for medical reasons was reported by slightly more than one percent of heterosexual women, 5 percent of lesbian/gay women and 5.5 percent of bisexual women.

Compared to heterosexual men (17 percent), past-year use marijuana was higher among bisexual men, (30 percent) and gay men (29 percent). Daily marijuana use among men was highest among bisexual men (9 percent) followed by gay (7 percent) and heterosexual men (4 percent). Any past-year medical marijuana use was 2 percent among heterosexual men, 5 percent among gay men and 4 percent among bisexual men.

Rates of daily marijuana use or marijuana use disorder for gay men did not differ significantly in states that had passed medical marijuana laws compared to states that had not passed these laws.

While beyond the scope of these analysis, the difference in policy effects of medical marijuana laws for bisexual women compared to heterosexual women may be a result of the high levels of stigma faced by bisexual women, according to the researchers. This could result in self-medication with medical marijuana even in states without MMLs if LGB adults are in part using marijuana to alleviate sexual minority stress.

"Our results support existing literature by demonstrating that bisexual women have higher marijuana use disorder compared to heterosexual women. This is part of a larger health burden, as bisexual women are twice as likely to have co-occurring mental health and substance use disorders yet often have little contact with service providers," observed Philbin.

"This study represents an important contribution to the literature on the structural determinants of substance use for LGB individuals and demonstrates the need to allocate resources that target sexual minority women, especially as medical marijuana laws and recreational marijuana laws continue to change at the state level," said Martins. "Future surveys that capture how individuals identify will help us pinpoint how state-level marijuana policies may differentially impact specific sub-populations, ultimately advancing the development of more health-promoting policies for all."

Computing--Assessing veteran suicide risk

In collaboration with the Department of Veterans Affairs, a team at Oak Ridge National Laboratory has expanded a VA-developed predictive computing model to identify veterans at risk of suicide and sped it up to run 300 times faster, a gain that could profoundly affect the VA's ability to reach susceptible veterans quickly. The model, called the medication possession ratio algorithm, creates individualized summaries of veterans' medication patterns. It helps clinicians pinpoint veterans with inconsistent medication usage who may have a higher risk of attempting suicide. With the accelerated model, "we can observe and reach a much larger population that's potentially at risk--and look at even more risk factors," ORNL's Edmon Begoli said. The sped-up version of the model can assess the behavior patterns of nine million veterans in only 15 minutes. "The potential to provide far greater predictive services is there," he added. [Contact: Rachel Harken, (865) 576-2057; harkenrm@ornl.gov]

Image: https://www.ornl.gov/sites/default/files/2019-08/VA_REACHVET1%5B6%5D.jpg

Caption: ORNL's project for the Department of Veterans Affairs bridges computing prowess and VA health data to speed up suicide risk screenings for United States veterans. Credit: Carlos Jones/Oak Ridge National Laboratory, U.S. Dept. of Energy

Transportation--Salting the gears

Researchers at Oak Ridge National Laboratory proved that a certain class of ionic liquids, when mixed with commercially available oils, can make gears run more efficiently with less noise and better durability. ORNL's team tested three different oil-soluble ionic liquids on steel under various temperatures, loads and speeds. They found that adding a small percentage of a phosphonium-phosphate ionic liquid into a gear oil can effectively reduce friction, wear loss, cracking, surface damage and associated vibration noises. "The current trend in lubrication is chasing better fuel economy by using less viscous lubricants," ORNL's Jun Qu said. "This ionic liquid resulted in oils that perform well with less viscosity, generating a thicker, smoother and more uniform film for superior surface protection." Results were published in ACS Applied Materials & Interfaces. [Contact: Jennifer Burke, (865) 576-3212; burkejj@ornl.gov]

Image: https://www.ornl.gov/sites/default/files/2019-09/Salting-the-gears_1.png

Caption: ORNL researchers used a low-viscosity base oil mixed with a small amount of phosphonium-phosphate ionic oil to test the lubricant's performance on steel. They found the ionic oil mix yielded less surface damage compared to lubrication with commercial gear oil. Credit: Jun Qu/Oak Ridge National Laboratory, U.S. Dept. of Energy

Neutrons--Lighting up liquid crystals

Researchers used neutron scattering at Oak Ridge National Laboratory's Spallation Neutron Source to probe the structure of a colorful new material that may pave the way for improved sensors and vivid displays. Most materials, including many biological photonic structures, exhibit structural colors as light moves through long-range periodic arrangements of elements in their microstructure. Yet, this material can produce striking colors using smaller, local arrangements of nanoplates. Thanks to this unique characteristic, researchers used the material to develop fluidic photonic art. "With neutrons, we saw firsthand how these nanoplates interact with light to form such spectacular colors," said Texas A&M researcher Zhengdong Cheng. "They were the perfect tools for developing an in-depth understanding of this material's microstructure." This discovery could be a significant development in the quest for advanced photonic materials. The research was published in Proceedings of the National Academy of Sciences of the United States of America. --Gage Taylor [Contact: Jeremy Rumsey, (865) 576-2038; rumseyjp@ornl.gov]

Image: https://www.ornl.gov/sites/default/files/2019-09/Neutrons-Lighting_up_liquid_crystals.jpg

Caption: An iridescent droplet of the nanoplate-based liquid crystals Zhengdong Cheng explored with his research team at ORNL's Spallation Neutron Source, a DOE User Facility. Credit: Mingfeng Chen/Texas A&M University and Oak Ridge National Laboratory, U.S. Dept. of Energy

Manufacturing--Layering on the strength

A team including Oak Ridge National Laboratory and University of Tennessee researchers demonstrated a novel 3D printing approach called Z-pinning that can increase the material's strength and toughness by more than three and a half times compared to conventional additive manufacturing processes. They demonstrated Z-pinning with polylactic acid, or PLA, and carbon fiber-reinforced PLA in a 3D printer designed for thermoplastic materials. With conventional 3D printing, the layer-by-layer building up of PLA materials can cause weaknesses between layers. Z-pinning allows continuous material to be deposited across multiple layers within the volume of the part. "The conventional layering approach can cause the strength of the material to decrease as much as 75%," ORNL's Vlastimil Kunc said. "The PLA sample with Z-pinning demonstrated uniform mechanical properties when measured in any direction. This technique can be used on any existing 3D printer." The team's results were published in the journal Additive Manufacturing. [Contact: Jennifer Burke, (865) 576-3212; burkejj@ornl.gov]

Image: https://www.ornl.gov/sites/default/files/2019-09/Z-pinning-printed%20wall_ORNL-2.png

Caption: The Z-pinning technique is used to insert reinforcing fibers along the Z-direction of continuous fiber-reinforced plastics. ORNL researchers used PLA to print a small wall, demonstrating that Z-pinning produces mechanically uniform properties when measured in any direction. Credit: Tyler Smith/Oak Ridge National Laboratory, U.S. Dept. of Energy

Tyrannosaurus rex, one of the largest meat-eating dinosaurs on the planet, had an air conditioner in its head, suggest scientists from the University of Missouri, Ohio University and University of Florida, while challenging over a century of previous beliefs.

In the past, scientists believed two large holes in the roof of a T. rex's skull -- called the dorsotemporal fenestra -- were filled with muscles that assist with jaw movements.

But that assertion puzzled Casey Holliday, a professor of anatomy in the MU School of Medicine and lead researcher on the study.

"It's really weird for a muscle to come up from the jaw, make a 90-degree turn, and go along the roof of the skull," Holliday said. "Yet, we now have a lot of compelling evidence for blood vessels in this area, based on our work with alligators and other reptiles."

Using thermal imaging -- devices that translate heat into visible light -- researchers examined alligators at the St. Augustine Alligator Farm Zoological Park in Florida. They believe their evidence offers a new theory and insight into the anatomy of a T. rex's head.

"An alligator's body heat depends on its environment," said Kent Vliet, coordinator of laboratories at the University of Florida's Department of Biology. "Therefore, we noticed when it was cooler and the alligators are trying to warm up, our thermal imaging showed big hot spots in these holes in the roof of their skull, indicating a rise in temperature. Yet, later in the day when it's warmer, the holes appear dark, like they were turned off to keep cool. This is consistent with prior evidence that alligators have a cross-current circulatory system -- or an internal thermostat, so to speak."

Holliday and his team took their thermal imaging data and examined fossilized remains of dinosaurs and crocodiles to see how this hole in the skull changed over time.

"We know that, similarly to the T. rex, alligators have holes on the roof of their skulls, and they are filled with blood vessels," said Larry Witmer, professor of anatomy at Ohio University's Heritage College of Osteopathic Medicine. "Yet, for over 100 years we've been putting muscles into a similar space with dinosaurs. By using some anatomy and physiology of current animals, we can show that we can overturn those early hypotheses about the anatomy of this part of the T. rex's skull."

In a new study published in PNAS, scientists from The Novo Nordisk Foundation Center for Biosustainability (DTU Biosustain) explored how different cell membrane transporters impact the production of dicarboxylic acids.

Currently, one of the problems in industrial biotechnology is that the transporters use too much energy on export, which decreases the overall product yield.

Transporter proteins are responsible for the transport of molecules across the cellular membranes. Transport processes are crucial for the growth of the cell and for the production of industrially relevant metabolites. The transport of organic acids typically requires energy.

"If you spend a lot of energy on export it will be more expensive to produce your compound, so from an industrial perspective it is very important to understand, which role these transporter proteins play," says Irina Borodina, Senior Researcher and Group Leader at The Novo Nordisk Foundation Center for Biosustainability (DTU Biosustain).

The scientists found that some transporters, such as MAE1 from Schizosaccharomyces pombe and DCT from Aspergillus carbonarius, improved the secretion of dicarboxylic acids in baker's yeast several fold, while not affecting the cellular growth. This came as a surprise to the researchers and made them speculate whether such transporters could possess a mechanism that allows them to use less energy.

Some families are more productive than others

The scientists discovered that these efficient transporters belong to the voltage-dependent slow-anion channel transporter (SLAC1) clade, which also encompasses plant transporters involved in stomata closure. In contrast to other sodium or proton-dependent dicarboxylic acid transporters, SLAC1 anion channels can transport anions with virtually no expense of energy.

In general, two SLAC1-type transporters operated with minimum energy use, and the study clearly suggests that energy usage of transporters should be considered when engineering cell factories.

Understanding the function of the yeast transportome

The next step is to build a library of all transporters, a so-called transportome, to cover all the approximately 340 transporter proteins of the model yeast Saccharomyces cerevisiae. As a part of a grant from The European Research Council YEAST-TRANS, the scientists will make it possible to screen and identify transporters of any desired bio-based product.

This knowledge will enable more efficient strain development as the movement of molecules by the different transporters within the cell and outside the cell can be controlled to some extent. Understanding the transporter function is essential not only for industrial biotechnology field but also for drug development. If the drug is taken up poorly by the target tissue or organ, it will be less efficient. Furthermore, if it accumulates in non-target tissues or organs, this will cause side effects.

In the future, when the scientists have gained more knowledge on the transport of small molecules, they will be able to make better predictions about the transport of drug candidates in the body and use this for more precise drug development.

Oral health is an essential part of psychological well-being and overall health in older adults. Poor oral health is associated with decreased quality of life, depression, hypertension, and cognitive decline. Two Rutgers studies, co-authored by Darina Petrovsky, Bei Wu, and Weiyu Mao, and published in the Journal of the American Geriatrics Society, explored the relationship between poor oral health and cognitive decline and the effects of perceived stress and social support on dry mouth among older Chinese Americans.

Researchers interviewed more than 2,700 Chinese Americans aged 60 and older and found that nearly 50 percent of study participants reported experiencing tooth symptoms, 25.5 percent reported dry mouth. In the first study, those who reported tooth symptoms experienced declines in cognition and episodic memory, often precursors to dementia. In the second study, the researchers found that stress increased symptoms of dry mouth, leading to poorer overall oral health.

"Racial and ethnic minorities are particularly vulnerable to the negative consequences of poor oral health," said XinQi Dong, director of Rutgers University's Institute for Health, Health Care Policy and Aging Research. "Minorities have less access to preventive dental care that is further exacerbated by language barriers and low socioeconomic status. Older Chinese Americans are at particular risk for experiencing oral health symptoms due to lack of dental insurance or not visiting a dental clinic regularly."

According to Dong, the increasing oral health disease burdens among older Chinese immigrants point to the need for investigations of psychosocial factors due to the current emphasis on physical diseases and health behaviors in oral health.

"Efforts must be made to increase social support to alleviate stress and the resulting dry mouth issues reported by our study participants," Dong continued. "These efforts can help preserve older adults' health and well-being and limit cognitive decline."

Key findings:

47.8 percent of older Chinese Americans reported having teeth symptoms; participants who reported teeth symptoms at baseline experienced their global cognition and episodic memory decline

18.9 percent of older Chinese Americans reported gum symptoms.

15.6 percent of older Chinese Americans reported teeth and gum symptoms.

25.5 percent of older Chinese Americans reported dry mouth.

More perceived stress was associated with higher odds of dry mouth.

"These studies demonstrate the importance of examining immigrant oral health outcomes later in life to understand the specific type of outcomes of different cultural groups," said Dong. "The studies further serve as a call to action for policymakers to develop programs aimed at improving oral health preventative and dental care services in this high-risk population. Darina Petrovsky, first author, added, "Examining current oral health practices among older Chinese Americans is crucial for developing culturally-tailored interventions to promote oral health and ultimately mitigate cognitive decline."

"Poor oral health is a top concern among older Chinese Americans. In our study, the prevalence rate of dry mouth is followed by diabetes and heart disease. Our findings demonstrate the importance of studying the linkage between stress and dry mouth in this vulnerable population." said author Weiyu Mao, Assistant Professor, School of Social Work, University of Nevada, Reno.

"Support from family and friends could be protective against dry mouth symptoms in relation to stress; however, the potential overload of such support could be detrimental to oral health outcomes among older Chinese Americans." Mao continued. "Intervention strategies need to expand beyond the common risk factors, such as health conditions and health behaviors, and account for the psychosocial determinants, including stress and social support, to better promote oral health and reduce oral health disparities in this population."

"Our research raises critical awareness for dental and healthcare providers of the role of perceived stress in dry mouth symptoms," added Dong. "Working collaboratively, dental, and healthcare providers can better identify oral health symptoms as risk factors of cognitive decline in this fast-growing vulnerable population. The primary focus should include promoting optimal oral health and improving the quality of life."

CORVALLIS, Ore. - Researchers at Oregon State University have made an important advance toward understanding why certain cells in the nervous system are prone to breaking down and dying, which is what happens in patients with ALS and other neurodegenerative disorders.

The study into the role a protein known as heat shock protein 90 plays in intracellular signaling is a key step on the way to figuring out the reason some motor neurons in the spinal cord die and some do not.

Findings, which could eventually lead to therapies to counter motor neuron death, were published in Experimental Biology and Medicine.

Neurons are cells in the nervous system that carry information to muscles, glands and other nerves. Motor neurons are large neurons in the spine and brain stem, with long axons extending outside the nervous system to contact muscles and control their movements via contraction.

Researchers led by Alvaro Estevez and Maria Clara Franco of the OSU College of Science have shown that a ubiquitous "protein chaperone," heat shock protein 90, is particularly sensitive to inhibition in motor neurons that depend for survival on "trophic factors" - small proteins that serve as helper molecules.

Trophic factors attach to docking sites on the surface of nerve cells, setting in motion processes that help keep a cell alive. Research in animal models has shown trophic factors may have the ability to salvage dying neurons.

"It is well known that there are some motor neuron subpopulations resistant to degeneration in ALS, and other subpopulations that are highly susceptible to degeneration," said Estevez, associate professor of biochemistry and biophysics and the corresponding author on this research. "Understanding the mechanisms involved in these different predispositions could provide new insight into how ALS progresses and open new alternatives for the development of novel treatments for the disease."

In this study, a motor-neuron-specific pool of heat shock protein 90, also known as Hsp90, repressed activation of a key cellular receptor and thus was shown to be critical to neuron survival; when Hsp90 was inhibited, motor neuron death was triggered.

The Hsp90 inhibitor used in this research was geldanamycin, an antitumor antibiotic used in chemotherapy. Findings suggest the drug may have the unintended consequence of decreasing motor neurons' trophic pathways and thus putting those nerve cells at risk.

"The inhibition of Hsp90 as a therapeutic approach may require the development of inhibitors that are more selective so the cancer cells are targeted and healthy motor neurons are not," said Franco, assistant professor of biochemistry and biophysics.

ALS, short for amyotrophic lateral sclerosis and also known as Lou Gehrig's disease, is caused by the deterioration and death of motor neurons in the spinal cord. It is progressive, debilitating and fatal.

ALS was first identified in the late 1800s and gained international recognition in 1939 when it was diagnosed in a mysteriously declining Gehrig, ending the Hall of Fame baseball career of the New York Yankees first baseman. Known as the Iron Horse for his durability - he hadn't missed a game in 15 seasons - Gehrig died two years later at age 37.

MAYWOOD, IL - A sepsis care quality improvement program saves lives, shortens hospital stays and reduces healthcare costs, according to a study by researchers at Loyola Medicine and Loyola University Chicago.

The study is published in the journal Critical Care Medicine.

Loyola's sepsis care quality improvement program includes a multidisciplinary sepsis committee, an education campaign, electronic health record tools and early warning system.

First author Majid Afshar, MD, MSCR, and colleagues examined records of 13,877 adult Loyola patients with suspected infections. Researchers compared outcomes of patients treated before and after the quality program was implemented.

Among patients treated after the quality improvement program began, the in-hospital death rate was 30 percent lower and time to discharge from the hospital was 25 percent faster. The program also was associated with a savings of $272,645 among patients with suspected infections.

Sepsis occurs when an infection triggers an extreme response throughout the body. Sepsis can lead to septic shock, a catastrophic drop in blood pressure that can lead to respiratory or heart failure, stroke, failure of other organs and death.

Sepsis is the leading cause of in-hospital mortality and the most expensive condition treated in the United States. It costs the country more than $24 billion per year.

In 2015, the Centers for Medicare and Medicaid Services (CMS) adopted guidelines for treating sepsis and septic shock that included early resuscitation and timely administration of antibiotics. For patients with severe sepsis, the hospital should obtain blood cultures, measure the patient's blood lactate levels and administer antibiotics within three hours of diagnosis. Hospitals should follow the same steps for patients with septic shock, plus take additional steps within six hours.

Loyola implemented its sepsis care quality improvement program in anticipation of the CMS three-hour and six-hour guidelines. Loyola's program includes education about the CMS guidelines; a sepsis early warning system in the electronic health records; the hiring of a sepsis coordinator; real-time physician feedback; and built-in features in the electronic health record system designed to improve adherence to the guidelines.

Loyola's program "may serve as a benchmark for other institutions to improve health outcomes and provide cost-effective care in patients with suspected infection or sepsis," Dr. Afshar and colleagues concluded.