Culture

A prognostic model developed using a machine learning approach could identify African-American breast cancer patients with increased risk of death, according to results of a study presented at the 11th AACR Conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, held here Nov. 2-5.

"Using gene expression data, we have developed a machine learning pattern to accurately stratify African-American breast cancer patients with high and low risks of death, which could help inform clinical decision making," said Shristi Bhattarai, PhD candidate in the lab of Ritu Aneja, PhD, at the Department of Biology, Georgia State University. "As African-American women tend to have worse breast cancer outcomes, this study will help us to identify race-based differences in this cohort, which could potentially lead to specific therapeutic regimens for African-American women with breast cancer."

While the incidence of breast cancer is similar between European-American and African- American women in the U.S., the age-adjusted mortality rates are 40 percent higher in African- American women with breast cancer, said Bhattarai. "The etiology of this startling outcome disparity is multifactorial, arising from the combination of socioeconomic inequality with inherently more aggressive tumor biology in women of African ancestry," she noted. "We wanted to identify a fingerprint that could stratify African-American breast cancer patients with different prognostic risks."

Utilizing data from The Cancer Proteome Atlas (TCPA), Bhattarai and colleagues analyzed protein expression levels of 224 proteins from 754 breast cancer patients. Of these patients, 620 were of European descent, and 134 were African-American. The algorithm they developed enabled the researchers to identify significant protein combinations that were associated with breast cancer survival, the authors explained.

The deep learning algorithm identified a combination of four proteins for optimal prognostic prediction: Bcl2-like protein (BAX), inositol polyphosphate-4-phosphatase, type II (INPP4B), X-ray repair cross-complementing protein 1 (XRCC1), and Cleaved Poly (ADP-ribose) polymerase (c-PARP). This combination of proteins could stratify high-risk African-American breast cancer patients with 86 percent accuracy.

"Interestingly, these proteins did not have a significant prognostic value individually," said co-author Sergey Klimov, PhD candidate in the lab of Ritu Aneja in the Department of Biology at Georgia State University. "However, their combined effect within the machine-learning model could identify an African-American cohort that had five times increased risk of death."

After controlling for clinicopathological variables including patients' age and cancer stage, the model could identify African-American women that had nearly 11 times increased risk of death.

The researchers were not able to stratify European-American breast cancer patients into low- and high-risk populations using this specific model, suggesting that this model is only prognostic for African-American breast cancer patients.

"We are moving toward the phase of clinical research where we can identify very specific patterns for understudied demographic groups to find high-risk patients so that they can be recruited for additional therapies," said Aneja. "We are excited that our model has the potential to inform clinicians to prioritize African-American breast cancer patients for appropriate clinical trials and also help patients make decisions about enrolling in specific clinical trials."

Limitations of this study include a lack of validation in other cohorts. "We will need to validate this model in different groups of African-American breast cancer patients," Aneja noted. "We want to make sure that this model is generalizable to different methodologies."

From the standpoint of heart health, the Tsimane are a model group. A population indigenous to the Bolivian Amazon, the Tsimane demonstrate next to no heart disease. They have minimal hypertension, low prevalence of obesity and and their cholesterol levels are relatively healthy. And those factors don't seem to change with age.

Also minimal is the incidence of Type-2 diabetes. Which leads scientists to consider the role of diet in the Tsimane's cardiovascular health -- and how it might be impacted over time as the population becomes more exposed to globalization and market forces.

That's where UC Santa Barbara anthropologists Thomas Kraft and Michael Gurven come in. They are part of the Tsimane Health and Life History Project, supported by the National Institutes of Health, which conducted the first systematic study that examines what the Tsimane consume on a regular basis and compares it to that of the Moseten, a neighboring population with similar language and ancestry, but whose eating habits and lifeways are more impacted by outside forces. The researchers' findings appear in the American Journal of Clinical Nutrition.

"Our prior work showed that the Tsimane have the healthiest hearts ever studied, so naturally there's a lot of interest in understanding why and how," said Michael Gurven, a professor of anthropology at UC Santa Barbara, co-director of the Tsimane Health and Life History Project and the paper's senior author. "The obvious first contender is, what are they eating? And are they eating what we think is best for heart health?

"We conducted a detailed analysis of the Tsimane diet and then compared it to what modern Americans typically eat, and to the diets that claim to be heart healthy," he continued. "Maybe the Tsimane just happen to follow one of those without knowing about them." These diets -- Paleo, Okinawan and DASH, among others -- are often promoted because of their proposed health benefits, and in the case of Paleo, that our bodies have evolved to benefit from particular types of food.

The connection to the Moseten is an added benefit of the study. Ethnolinguistically and genetically very similar to the Tsimane, the Moseten, an isolate in Bolivia, are much more acculturated in a number of ways than are the Tsimane. "They provide a forecast of what Tsimane health might look like 20 years from now," Gurven said. "They represent what is happening to many indigenous populations over time. To what extent may changes in their diet increase the prevalence of heart disease and diabetes?"

Using the same measurement strategy employed by the U.S. Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey, the researchers interviewed 1,299 Tsimane and 229 Moseten multiple times about everything they had eaten or drunk in the previous 24 hours. Using published and their own nutritional estimates for all items, and a variety of methods to estimate portion size, they provided a detailed breakdown of daily food intake.

The high-calorie (2,433-2,738 kcal/day) Tsimane diet was characterized by high carbohydrate and protein intake, and low fat intake (64, 21 and 15 percent of the diet, respectively). In addition, the Tsimane don't eat a wide variety of foods, relative to the average U.S. or Moseten diet. Almost two-thirds of their calories are derived from complex carbohydrates, particularly plantains and rice. Another 16 percent comes from over 40 species of fish, and 6 percent from wild game. Only 8 percent of the diet came from markets.

Despite the low dietary diversity, the researchers found little evidence of micronutrient deficiencies in the Tsimane's daily intake. Calcium and a few vitamins (D, E and K) were in short supply, but the intake of potassium, magnesium and selenium -- often linked to cardiovascular health -- far exceeded U.S. levels. Dietary fiber intake was almost double U.S. and Moseten levels.

Over the five years of study, the researchers saw the Tsimane's total energy and carbohydrate intake increase significantly, particularly in villages near market towns. Their consumption of food additives (lard, oil, sugar and salt) also has increased significantly. The Moseten, the researchers noted, consumed substantially more sugar and cooking oil than did the Tsimane.

The conclusion: A high-energy diet rich in complex carbohydrates is associated with low cardiovascular disease risk, at least when coupled with a physically active lifestyle (Tsimane adults average 17,000 or so steps per day, compared to Americans' 5,100). Moving away from a diet that is high in fiber and low in fat, salt and processed sugar represents a serious health risk for transitioning populations. Evidence of nutrition transition in Bolivia parallels trends in increasing body fat and body mass index among Tsimane, suggesting the low prevalence of cardiovascular disease -- as among the Tsimane -- may not persist.

According to Gurven, avoiding the pitfalls of changing diets and lifestyles will be critical for groups like the Tsimane. Many other indigenous populations in South America, Africa and Southeast Asia are in similar situations. And rates of obesity, type-2 diabetes and heart disease are high among indigenous groups whose lifeways are no longer traditional -- including many North American Indian and Australian aboriginal populations.

And for the Tsimane, change is not far on the horizon. "This is a key time," said Thomas Kraft, a postdoctoral researcher in anthropology at UC Santa Barbara and the paper's lead author. "Roads are improving in the area, as is river transport with the spread of motorized boats, so people are becoming a lot less isolated compared to the past. And it's happening at a pretty rapid pace."

Anecdotally, Gurven added, the Tsimane Health and Life History Project's biomedical team is seeing more diabetic patients among the Tsimane than they have previously. That's likely due to the increased regular intake of refined sugar and fat that occurred over the course of the study. As Kraft noted, with the Tsimane's ability to buy large kilo bags of sugar and liters of cooking oil, the researchers calculated a 300 percent rise in consumption of those products. "They're basically deep frying and adding lots of sugar to drinks when they can," he said.

And consuming a lot of calories. "But they're also physically active -- not from routine exercise, but from using their bodies to acquire food from their fields and the forest," added Gurven, "which is also an important lesson. You can't look at what you're eating irrespective of what you're doing with your body. If you're physically active, you can probably get away with more flexibility in the diet."

Calorie count aside, the high carbohydrate content of the Tsimane diet isn't "unprecedented," according to Kraft. "One of the other artery-protecting diets is the Okinawan diet from Japan. It comes out at about 85 percent carbohydrate. But a common feature they share is that pretty much across the board, they're complex carbohydrates -- it's sweet potatoes in the Okinawan diet; here it's plantains and manioc."

The Moseten diet has fewer total calories and less carbohydrates than the Tsimane diet, but the Moseten eat a broader range offoods, including more fruits, vegetables, dairy and legumes. The Moseten also buy more of their food, including soda, bread, dried meat and processed items. The Moseten diet could provide insight into the Tsimane diet of the future, the researchers suggest. "We're still analyzing their health indicators, but we expect the Moseten to show more risk factors related to diabetes and heart disease," said Gurven.

In addition to finding that the Tsimane consume more calories per day than the Moseten do, the researchers note the Tsimane are also more physically active (with much of their labor devoted to the hard work of slash and burn farming, hunting, fishing and foraging). They expend more energy activity, but may also have a higher resting energy expenditure due to higher rates of infection and persistent immune activity.

Overall, the findings suggest that no single diet protocol offers the key to health. The picture is much more complicated. "It definitely sheds light on the diversity of diets that are compatible with good cardiovascular health," said Kraft.

Added Gurven, "We're at a unique point in history where for many of us, our daily decisions are more about what not to eat. We have to work hard not to overeat. Throughout most of human history, it was the opposite. It was so hard to get those calories we needed to survive."

And in terms of the Tsimane's eagerness to incorporate sugar and other additives into their diets despite the associated health risks, "Telling folks to watch what they're eating, don't eat too much of this or that -- that mentality is hard to convey when getting food is unpredictable and a daily grind," Gurven continued. "Getting calories cheaply with less effort -- who wouldn't?"

CHAMPAIGN, Ill. -- Demographic and cultural differences strongly influence the coping styles young people use when they're affected by a natural disaster, and these disparities should be taken into account when providing services to help them recover from these traumatic experiences, a new study found.

University of Illinois social work professors Tara M. Powell and Kate M. Wegmann led the study, which utilized a new method of assessing coping among disaster-affected youths to address the limitations of a commonly used survey called Kidcope.

"We know that the way a kid copes after a disaster determines how well they're going to overcome the experience or whether they develop problems such as post-traumatic stress disorder, depression or anxiety," Powell said. "However, one of the things that we don't know is the best measure that researchers and clinicians can use to assess young people's post-disaster coping methods."

The current study explored the coping strategies used by middle-class teen girls in St. Tammany Parish, an affluent area of New Orleans, after the area was damaged by Hurricane Katrina in 2005. Of the 650 girls in the study, about 82 percent reported that the hurricane forced their families to evacuate their homes.

Six months after Katrina, the girls completed an adapted version of the Kidcope assessment, a survey widely used by clinicians and researchers to examine children's and adolescents' use of behaviors such as distraction, social withdrawal and social support to handle major stressors, including natural disasters.

However, one limitation of Kidcope is that it was designed for use in clinical settings to examine young people's coping with serious illnesses and lengthy hospitalizations - contexts that differ from natural disasters, the researchers wrote.

When used in prior studies to assess coping among hurricane-affected youths, Kidcope's structural modeling was variable and unstable, according to Powell and Wegmann. To address these inconsistencies, they and co-author Stacy Overstreet of Tulane University tested three different structural models to find the best fit with their study population of young hurricane survivors.

They found that the coping strategies utilized by the girls in St. Tammany Parish resembled a four-factor structural model, which included positive coping behaviors along with less healthy externalizing behaviors such as blame and anger, wishful thinking and social withdrawal.

In comparing these girls' coping behaviors with those used by a sample of low-income, predominantly African-American peers who also survived Hurricane Katrina, the researchers found few similarities.

Instead, the St. Tammany Parish girls' coping methods were consistent with those used by middle-class youths who were affected by a different natural disaster - Hurricane Andrew, which struck the Bahamas, Florida and Louisiana in 1992, Wegmann said.

"We found that culture really matters in terms of how adolescents respond to a disaster," Wegmann said. "Some of the cultural values that are associated with resilience, such as a focus on community and informal means of support, are less prominent among middle-class populations than lower income populations.

"Middle class and wealthier demographics' cultural values are more about individualism and personal responsibility, so the communalism that can help a person recover from a disaster just isn't there," Wegmann said.

By utilizing a data analysis technique called "exploratory structural equation modeling," the researchers found that the behavioral strategies the St. Tammany Parish girls used also had complex relationships with each other.

For example, the coping strategy of attempting to forget about the problem, which was associated primarily with social withdrawal, also was associated with wishful thinking, blame and anger, and positive coping.

Understanding how and why disaster victims utilize varying coping methods and the influences that demographic differences may have on their responses is hampered by the lack of consistent, reliable assessment tools, according to the authors.

Developing effective, well-validated measures that can be distributed easily and adapted for differing populations should become a research priority to better assist disaster survivors with recovery, Powell and Wegmann said.

Boston, MA -- To be more transparent and to promote communication with patients after medical injuries, many hospitals have implemented a new approach called the communication-and-resolution program (CRP). Through these programs, hospitals openly communicate with patients after adverse events, investigating specifics, providing explanations, and, when necessary, taking responsibility and proactively offering compensation. Medical centers that have adopted this program believe it will help to improve patient safety and that it is the hospital's ethical obligation to disclose medical errors. However, some medical centers are wary that willingly admitting errors could result in increased liability costs. Continuing uncertainty about this issue has continued to be a barrier to the widespread adoption of this program.

A team of researchers at Brigham and Women's Hospital, Baystate Medical Center (BMC), Beth Israel Deaconess Medical Center (BIDMC), Stanford Health Care, and Ariadne Labs, evaluated the liability effects of these communication-and-resolution programs at four Massachusetts hospitals. Their results, published today in a special, "patient safety" edition of Health Affairs, found that these programs were associated with improved trends in the rate of new claims and legal defense costs at some of the sites. And they found that the approach did not expand liability risk at any of the sites. The program allowed these organizations to fulfill their ethical obligations to disclose adverse events and promote patient safety without encountering negative liability consequences.

"The CRP approach allows hospitals to 'do the right thing' -- be honest about errors, apologize, and compensate patients who are injured by negligence - without adverse financial consequences," said Allen Kachalia, MD, JD, chief quality officer at Brigham and Women's Hospital and first author on the paper.

A communication-and-resolution program known as CARe (Communication, Apology, and Resolution) was implemented at BMC and BIDMC, and at two of each center's community hospitals (Baystate Franklin Medical Center, Baystate Mary Lane Hospital, Beth Israel Deaconess Hospital-Milton, and Beth Israel Deaconess Hospital-Needham). The team examined the effect of CARe's malpractice claims volume, compensation and legal defense costs, and the time it took to find resolutions. They compared trends in the six years before CARe and then a few years after implementation at each institution. They calculated several quarterly rates for each hospital: new claims, new claims receiving compensation, compensation cost, defense cost, total liability cost, and average compensation cost. A claim was defined as any written request for patient compensation that was brought to the liability insurer, whether initiated by the patient, family, or hospital. This is the first study of its kind that involves two centers in one state and includes comparison groups.

After CARe implementation, the team found there was a significant decrease in the rate of new claims at the implementing community hospitals and academic medical centers, a change that was not seen at hospitals that did not implement CARe. Both academic medical centers experienced a significant decrease for defense costs after CARe implementation. Additionally, there were no significant changes in total liability costs observed nor in the average compensation amount per paid claim at any of the hospitals.

"Our hope is that with these findings, more hospitals will have greater confidence that communicating openly with patients around errors and injury is not likely to create greater liability risk," said Kachalia.

In its special edition, Health Affairs also published papers by David Bates, MD, and Gordon Schiff, MD, on patient safety concerns:

Bates' paper, "Two Decades Since To Err Is Human: An Assessment Of Progress And Emerging Priorities In Patient Safety," reviews the Institute of Medicine's "To Err Is Human" report, which initially brought the problem of patient safety into the public eye 20 years ago. Some of the areas the paper reviews include the evolving identification of patient safety issues, the development and adaptation of effective interventions for hospital-acquired infections, and the emergence of new safety risk areas, including diagnostic error and technology-related concerns.

In Schiff's paper, entitled "A Prescription for Enhancing Electronic Prescribing Safety," he and a team of clinicians, communications safety, and health IT experts outlined six steps and areas of improvement to a safer and easier electronic prescribing system that could lead to fewer errors and better cost-effectiveness.

NEW ORLEANS --Latinos in the United States experienced an overall increased risk of cancer death with each generation born in this country, according to results of a study presented at the 11th AACR Conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, held here Nov. 2-5.

"Latinos are the largest and the fastest growing minority population in the United States, and cancer is the leading cause of death among this population, accounting for 21 percent of deaths in 2016," said the study's lead author, V. Wendy Setiawan, PhD, associate professor of preventive medicine, Keck School of Medicine, University of Southern California in Los Angeles. "In spite of this, cancer-related factors affecting Latinos remain understudied in contrast to other racial/ethnic populations in the U.S.," she added.

Previous research has shown that U.S.-born Latinos have higher incidence of cancer than foreign-born Latinos. To gain more information on the influence of acculturation and environmental factors, Setiawan and colleagues examined cancer mortality patterns across first-generation immigrants, and second- and third-generation U.S.-born Mexican Americans in the Multiethnic Cohort Study, a long-term study funded by the National Cancer Institute.

The researchers studied 29,308 Latinos of Mexican origin, aged 45-74 when they entered the cohort. During an average follow-up of 17.7 years, 2,915 cancer deaths were identified.

The study showed that the highest cancer death rate occurred among third-generation U.S.-born Latinos (537 per 100,000), followed by second-generation Latinos with one parent born in Mexico (526 per 100,000) or both parents born in Mexico (481 per 100,000). The lowest cancer death rate occurred among first-generation immigrants (381 per 100,000).

The study also showed trends in certain cancer types. The risk of lung, colorectal, and liver cancer deaths were significantly higher among third-generation U.S.-born Latinos compared with the first-generation Mexico-born immigrants. Setiawan said these cancers are often caused by environmental factors, which could explain the more pronounced risks through several generations.

"Diet, lifestyle, and environmental changes as individuals become more acculturated to the American way of life may contribute to these higher rates among the third-generation immigrants," Setiawan said.

The risks of prostate, stomach, and pancreatic cancer deaths were similar across all generations, Setiawan added.

She said this study adds to previous research that has shown how acculturation and environmental factors have affected the growing Latino population.

"The disparities in cancer mortality we observed in U.S. Latinos are likely due to changes in lifestyle, health behaviors, and social factors," Setiawan said. "This study is a reminder that some factors that contribute to cancer risk are modifiable."

Setiawan cautioned that as an observational study, this work does not prove that successive generations of Latino immigrants in the United States face increased risk of cancer mortality. She said future research will examine a combination of risk factors, including lifestyle, migration history, genetic ancestry, and social and contextual factors.

Researchers from the Netherlands Institute for Neuroscience and Amsterdam UMC have disclosed the nature of how T cells protect the brain against harmful viruses. The results of the study, which are published in Nature Communications, are important for investigating the role of the immune system in numerous brain disorders.

Immune system

The immune system protects the body against infections and cancer. The so-called T cells play a key role in this process. When T cells do not work properly, an inflammation can develop in for example the brain. Until recently, little was known about the properties of these cells in healthy brains. "With this research, we have gained more knowledge about the location of T cells in the brain, how they look, what kind of inflammatory proteins (cytokines) they produce, and how they are controlled," says researcher and neurologist in training Joost Smolders.

The scientists have found that the two proteins CTLA-4 and PD-1 are present in large quantities on T cells. These proteins, for which the Nobel Prize for Medicine has been awarded to the discoverers this year, are important inhibitors for T cells.

"If we understand the rules of the game, which T cells in the brain adhere to, then we can understand how T cells deviate from this in brain disorders. This can lead to advances in the understanding and treatment of diseases such as multiple sclerosis, but also in the treatment of tumors in the brain. "

Brain donors

With financial support from the MS Research Foundation, the scientists have investigated T cells from brain tissue of brain donors from the Netherlands Brain Bank (NBB). "For the understanding of the role of the immune system in brain disorders, a donor program such as the NBB is of crucial importance. The quality of the material makes unique research possible" says Smolders.

When you park in the office car park, you usually have no problem finding your car again at the end of the day. The next day, you might park a few spots further away. However, in the evening, you find your car, even though the memories of both days are very similar. You find your car (also) because our brains are able to store memories of very similar events as distinct memories in a process called pattern separation. Researchers at the Institute of Science and Technology Austria (IST Austria) are deciphering how the brain computes this pattern separation in a brain region called the dentate gyrus. Results of their work are published today in Nature Communications.

Peter Jonas and his team, including first author and PhD student Claudia Espinoza, Jose Guzman, previously Postdoc in the Jonas group and now Research Associate at IMBA and Xiaomin Zhang, currently Postdoc in the Jonas group sought to understand how the connections between neurons in the dentate gyrus, a part of the hippocampus and the brain region required for pattern separation, allow the dentate gyrus to separate patterns in mice.

In the dentate gyrus, two types of neurons send signals: principal neurons send excitatory signals, while interneurons send inhibitory signals. The researchers sought to decipher the rules of connectivity between them - which neurons send signals to each other, are connections between neurons reciprocal or do many neurons converge to send signals to one main neuron? They recorded signaling between neurons to understand how the neurons are connected and how the local circuit works to support pattern separation. Espinoza performed octuple whole-cell recordings, in which she stimulated one neuron in a slice of the dentate gyrus, and recorded how the other seven neurons respond. By labelling all stimulated neurons, she could then reconstruct the morphology of the circuit.

The researchers found that one group of interneurons, the parvalbumin-expressing interneurons, are connected in a specific way only in the dentate gyrus. In the dentate gyrus, parvalbumin-expressing interneurons mainly inhibit the activity of nearby neurons in a process called lateral inhibition. In other brain regions, such as the neocortex, parvalbumin-expressing interneurons are not connected in this manner. "We think that the unique connectivity rules established by parvalbumin-expressing interneurons, such as lateral inhibition, represent a circuit adaptation to specific network functions that occur in this brain region", explains Claudia Espinoza, "Our experimental data supports the idea that pattern separation works through a mechanism called 'winner-takes-it-all', achieved via lateral inhibition in the dentate gyrus. However, this has not been proven yet. We need behavioral data and computational models, which we are working on."

After the dentate gyrus separates similar memories to avoid an overlap between them, the CA3 region of the hippocampus then stores these memories. In a previous article published in Science in 2016, Peter Jonas and Jose Guzman showed that the connectivity in the CA3 region of the hippocampus is designed to recall information of stored memories in a process called pattern completion. "At a biological level, our group found the connectivity rules that support the computational function of a brain region", says Espinoza, "Our work contributes to showing how local circuits are optimized for the specific function of a brain area. While the input that reaches the dentate gyrus is important, the way in which the dentate gyrus then computes this information to achieve pattern separation is crucial."

Claudia Espinoza is a PhD student in the group of Peter Jonas. Before Claudia Espinoza joined IST Austria for her PhD studies in 2013, she worked with patients with neurological disorders. This experience motivated Espinoza to pursue a PhD in neuroscience: "I realized that my work as a therapist was very limited because the treatment that we could offer to our patients was very scarce, and actually most of the available treatments are palliative and not curative. The main reason is that the information available about how the nervous system works is very limited, more than what most people believe. This fact motivated me the most for changing my career from a therapist to a researcher. I think that creating knowledge is a beautiful way of contributing something to our society and indirectly to helping people." IST Austria's interdisciplinary graduate school offers fully-funded PhD positions in the natural and mathematical sciences. Applications for the next year of study at the IST Austria graduate school start in mid-October: phd.ist.ac.at

NEW ORLEANS -- An interactive online LGBT cultural competency training program for oncologists may be acceptable, feasible, and improve LGBT-related knowledge and clinical practices, according to preliminary results of a pilot study of oncologists in Florida to be presented at the 11th AACR Conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, held here Nov. 2-5.

The training program was developed via an interdisciplinary collaboration between investigators at the Sylvester Comprehensive Cancer Center in Miami; the H. Lee Moffitt Cancer Center and Research Institute in Tampa; and the University of Florida Cancer Center in Gainesville.

"LGBT people experience substantial health disparities in various cancer survivorship and quality of life outcomes, including reporting more distress, more relationship difficulties, and less satisfaction with their cancer treatment and care than their heterosexual and cisgender counterparts," said Julia Seay, PhD, research assistant professor at the Sylvester Comprehensive Cancer Center. "As part of a broader effort to address disparities and improve cancer care and survivorship among LGBT people, we are working to improve LGBT cultural competency among oncologists."

LGBT competency involves having the knowledge and ability to work effectively with LGBT patients, explained Seay. It is an evolving skill set that involves not only knowledge about the unique care needs of sexual and gender minority individuals, but also the communication skills to effectively provide high-quality, personalized care for LGBT patients.

Seay's colleagues, Matthew Schabath, PhD, associate member in the Department of Cancer Epidemiology at the H. Lee Moffitt Cancer Center and Research Institute, and Gwendolyn Quinn, PhD, the Livia S. Wan, MD, Professor of Obstetrics and Gynecology in the Department of Obstetrics and Gynecology at New York University Langone Medical Center, previously conducted a national survey of oncologists and found that the overwhelming majority would be willing to receive training on the unique care needs of LGBT patients. This led them to design the interactive online LGBT cultural competency training program.

The training program comprises four 30-minute modules. Two of the modules cover general topics, such as sexual orientation and gender identity terminology. The other two are oncology-focused; they include topics such as hormone therapy considerations for transgender patients undergoing cancer treatment and discussions of fertility with LGBT patients within the context of cancer care.

To date, Seay and colleagues have recruited 20 oncologists from Sylvester Comprehensive Cancer Center, Moffitt Cancer Center, and UF Health Cancer Center to participate in the online training and provide feedback via self-administered questionnaire. Among the participating oncologists, 75 percent were heterosexual and cisgender.

Oncologists' LGBT-related knowledge increased after completion of the training: The proportion of participants who correctly answered more than 90 percent of LGBT-related knowledge items was 33 percent before training and 85 percent after training.

LGBT-related attitudes and clinical practices were also improved after completing the training: 70 percent of participants reported an increase in favorable perspectives toward LGBT people and 80 percent reported increasing their endorsement of LGBT-serving clinical practices.

In addition, after completing the training, 90 percent of the oncologists rated the training as either "excellent" or "very good," and 95 percent stated that they would refer another oncologist to the training.

"These descriptive data from our pilot study show that this training program is both feasible and acceptable for oncologists," said Seay. "The preliminary analyses also showed positive pre-post changes in LGBT-related knowledge and clinical practices. We hope to have the formal significance testing analysis completed in advance of the conference."

According to Seay, the main limitation of the study is that it is a pilot study that involved a relatively small sample of oncologists from three institutions in the state of Florida. "This limits our ability to draw conclusions regarding the effectiveness of the training and the findings may not be broadly applicable to oncologists across the United States. However, we are hoping to soon be able to examine the effectiveness of our training among oncologists nationally," said Seay.

Compared with U.S. states with the strictest gun control legislation, gun deaths among children and teenagers are twice as common in states with the most lax gun laws, a study from the Stanford University School of Medicine has found.

In addition, states with laws that restrict children's access to guns have lower rates of firearm-related suicides among youth, even after controlling for other factors, the study said.

The research will be presented in a scientific talk Nov. 5 at the American Academy of Pediatrics 2018 National Conference & Exhibition in Orlando, Florida.

The title of the presentation is "Strict Firearm Legislation Is Associated With Lower Firearm-Related Fatalities Among Children and Teens in the United States."

"A child is 82 times more likely to die in our country of a firearm injury than in any other developed nation," said senior author Stephanie Chao, MD, assistant professor of surgery at Stanford. "We focus a lot on the federal government and the things they can do to protect our children from firearms. But our study shows that what states do at the state level really does have an impact."

The lead authors of the study are former graduate student Sriraman Madhavan and postdoctoral scholar Jordan Taylor, MD.

Chao, a pediatric surgeon, is the medical director of trauma care at Lucile Packard Children's Hospital Stanford, where her role includes investigating how to prevent serious childhood injuries. "If you look at what causes injury deaths in U.S. children, sadly, firearms are always in the top five," she said.

Gun death data

Chao's team used 2014 and 2015 data on firearm deaths of individuals 0 to 19 years old from the National Vital Statistics System, which is maintained by the Centers for Disease Control's National Center for Health Statistics. About 2,715 children died of firearm injuries each year. Of those deaths, 62.1 percent were homicides, 31.4 percent were suicides and the remaining deaths were accidental, of undetermined intent or the result of legal interventions.

The researchers examined the firearm laws of all 50 states. They rated the overall stringency of each state's gun laws as of 2014 using a metric called the Brady score, which ranged from -39 in the least strict state, Arizona, to +76 in the strictest state, California. (The score is named for James Brady, who has advocated for gun control since being permanently disabled in the 1981 assassination attempt on Ronald Reagan.) The researchers also evaluated whether each state had child access prevention laws, which were classified in two groups: legislation that requires storing guns safely (locked or unloaded, or both), and laws that impose liability for failing to prevent minors from gaining access to guns.

Analyses of the relationship between gun deaths and gun laws were controlled for many socioeconomic and demographic factors, including unemployment rates, poverty, urbanization, alcohol dependence, tobacco and marijuana use, and high school graduation rates. The analyses also accounted for the strictness of gun laws in each state's neighboring states and the number of registered firearms per 100,000 children in each state.

The researchers grouped the states by Brady score. Before adjusting for socioeconomic and demographic factors, the states in the highest quartile -- with the strictest laws -- had an annual youth firearm mortality rate of 2.6 per 100,000, while states in the lowest quartile, with the least strict laws, had nearly twice that mortality rate, at 5.0 per 100,000. States' Brady scores were still significantly correlated with pediatric gun deaths after controlling for other factors.

States with both types of child access prevention laws had pediatric firearm suicide rates of 0.63 per year per 100,000 children, while states that had no CAP laws had 2.57 pediatric firearm suicides per year per 100,000 children. The relationship was significant even after controlling for other factors, the study found.

Chao hopes the work will inform state-level legislators. "If you put more regulations on firearms, it does make a difference," she said. "It does end up saving children's lives."

NEW ORLEANS -- African-Americans caring for loved ones with cancer were less likely than their white peers to report distress and depression, possibly due to stronger social support, according to results of a study presented at the 11th AACR Conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, held here Nov. 2-5.

"Informal caregivers, generally family members or friends, play an increasingly large role in the care of cancer patients," said the study's co-lead author, Maria Thomson, PhD, assistant professor in the Department of Health Behavior and Policy at Virginia Commonwealth University in Richmond.

"We do not have a good understanding of exactly how burdensome this is, how it affects caregiver health and economic outcomes over time, or which aspects caregivers view as particularly burdensome," she continued.

To compare perceived burden, depression, and distress between African-American and white informal caregivers, Thomson and colleagues enrolled 90 caregivers, 44 African-American and 46 white, all of whom were providing end-of-life care to cancer patients. They surveyed the caregivers on demographics, preparedness for caregiving, and distress, and rated them on the CES-D scale for depression and the Zarit Burden scale for caregiver burden.

The African-American caregivers reported significantly lower distress, depression, and caregiver burden. Overall, older caregivers reported lower levels of distress than younger caregivers.

Thomson said that preparation for the caregiving role was a major factor in the respondents' mental and emotional well-being. She said caregivers of any race who felt they had received adequate information, training, and support regarding the caregiving role were significantly less likely to report distress.

Religiosity also played a role, with African-American caregivers more likely to identify church or faith-based groups as a source of social support compared with white caregivers. The authors said this finding could help inform future interventions to support caregivers.

"Finding that African-American caregivers reported lower levels of caregiver burden and depression, as compared to white caregivers, is important for understanding how to develop effective caregiver supports," said first author Laura A. Siminoff, PhD, dean of the College of Public Health at Temple University in Philadelphia.

"This illustrates that there are likely to be important sociocultural differences in the ways in which caregivers experience and attach meaning to caregiving, where they prefer to seek support, and the types of support that would be most helpful," she added.

The authors cautioned that this study represents preliminary findings from a larger, ongoing study. They anticipate that the broader study will provide more complete information on how caregivers fare over time and which factors affect their emotional and mental health.

Thomson and Siminoff added that racial and ethnic minorities are underrepresented in existing research on cancer caregivers, and future research should aim for more diverse, representative samples.

DALLAS, Nov. 1, 2018 -- Hospitalized ischemic stroke patients with an infection are significantly more likely to be readmitted within 30 days, regardless of the severity of their stroke or other individual patient characteristics, according to new research published in the American Heart Association's journal Stroke.

Ischemic strokes are caused by a blockage in an artery leading to the brain and are the most common type of stroke.

Researchers reviewed 319,317 stroke patient records in the 2013 National Readmission Database to determine if there was a relationship between in-hospital infections, such as sepsis (an infection in the blood), pneumonia, respiratory and urinary tract infections, and being readmitted to the hospital within 30-days. They found that any infection developed while hospitalized was associated with a 20 percent higher risk of 30-day readmission after being adjusted for other factors linked to rehospitalization. When the researchers investigated specific types of infections, they found that more common infections, such as urinary tract infections, increased the risk of 30-day by 10 percent.

"Although our study had some limitations, it appears that ischemic stroke patients who develop a urinary tract infection in the hospital may be candidates for earlier follow-up and closer monitoring by their healthcare team," said Amelia K. Boehme, Ph.D., lead researcher and assistant professor of epidemiology in neurology at Columbia University Mailman School of Public Health in New York, New York. "We suspect the reason the association was so much stronger for urinary tract infections was that urinary tract infections are very common compared to other infections, so the association was significant."

This study highlights the importance of nursing and admission protocols targeted at preventing urinary tract infections, such as avoiding the use of indwelling catheters (which is a type of catheter inserted into the bladder when a person cannot urinate) as well as performing bladder ultrasounds to diagnose urinary retention. These strategies may help prevent 30-day re-admissions, particularly if they are carried forward in rehabilitation centers or at home, Boehme said.

Serotonin (3A) receptors are common drug targets in the treatment of pain, gastrointestinal dysfunctions, and mood disorders yet little is known about their three-dimensional structure. Details about serotonin receptor structures could provide important clues to designing better drugs with less side effects. Now, a team of researchers from Case Western Reserve University School of Medicine have used high-powered microscopes to view serotonin activating its receptor for the first time. Images published in Nature reveal molecular details about the receptor that could improve drug design to treat a multitude of diseases.

Serotonin receptors sit in cell membranes throughout the body, including the brain, stomach, and the associated nervous system. Drugs that inhibit serotonin receptors help control post-operative nausea, support cancer therapies, and are used to treat gastrointestinal conditions like irritable bowel syndrome. These inhibitors also find application as anti-depressants, and promote attention and memory.

Broad application comes with side effects--in part due to suboptimal drug-receptor interactions, says study lead Sudha Chakrapani, PhD, associate professor of physiology and biophysics at Case Western Reserve University School of Medicine. "Successful design of safer therapeutics has been slowed because there is a limited understanding of the structure of the serotonin receptor itself, and what happens after serotonin binds to it. Our work is the first to describe how serotonin activates the full-length serotonin receptor at a level of detail to nearly the individual atom."

Using Nobel Prize-winning microscope technology, Chakrapani's team studied serotonin as it interacted with its receptor. Their images show serotonin attaching to the receptor and twisting open the channel. Open channels allow molecules to travel from outside the cell to inside. The researchers used simulations to watch as sodium molecules traveled through newly opened channels. The new study highlights distinct conformations of the serotonin receptor that would make a cell more or less permeable to certain molecules--a key insight for drug developers. It also shows which portions of the receptor are most critical for proper channel function.

The entire serotonin-receptor occurs in a space about a few billionths of a meter across. Microscopes have only recently evolved to capture such tiny molecules. Cutting-edge technology in the new study--cryo-electron microscopy--earned a 2017 Nobel Prize in chemistry. It uses high-powered microscopes to take snapshots of proteins in action, and compiles them into three-dimensional structural models. In the past year it has already helped Case Western Reserve researchers view structures for proteins central to kidney stones and other ailments. Chakrapani used "cryo-EM" last year to view the serotonin receptor alone, laying the foundation for the present study.

The researchers hope their findings could lead to more precise drugs that target specific regions or functions of serotonin receptors. "It's likely that new and different drugs can work as effective serotonin inhibitors, especially if they're designed to work differently than current drugs," says first author Sandip Basak, PhD, postdoctoral fellow in Chakrapani's lab. "We're actively pursuing these approaches to help design safer therapeutics that modulate the serotonin receptor to treat a range of conditions."

A new study published in Proceedings of the National Academy of Sciences could change the way scientists look at one of the most essential enzymes in medicine in hopes of designing better and more cost-effective drugs in the future.

Enzymes are molecules that speed up chemical reactions inside cells. The human body is home to thousands of enzymes that perform vital functions such as the digestion of fat and the breakdown of sugar into glucose.

The paper, co-authored by UT Biochemistry and Cellular and Molecular Biology Associate Professor Nitin Jain and student Sara Lemmonds, who has since graduated, looks closely at Cytochrome P450, an enzyme that occurs naturally in the body and other environments. This enzyme is critical in metabolizing over 90 percent of all pharmaceutical drugs.

When a drug is administered, it is usually not used up entirely by the body, and the residual excess can become toxic. "It is P450's job to bind with the leftover drug in the liver to ensure that it is safely excreted," explained Lemmonds.

Scientists know that P450 has another remarkable feature: it can remain stable under very high heat. The same enzyme has been found in bacteria in hot springs and volcanic deposits and has been observed to function normally despite extreme temperatures.

The UT researchers are honing in on the enzyme's heat tolerance.

"The chemical reactions produced by human P450 enzymes are more efficient when they occur at increasing temperatures," said Jain.

Up until now, scientists believed that P450's tolerance to heat had its origin in its rigid structure. However, Jain and Lemmonds's study suggests that these proteins may be quite flexible.

"By better understanding the relationship between flexibility and high temperature, scientists can engineer improved P450 enzymes targeted at biotechnology applications and designing better drugs for humans, producing them en masse and making them more cost effective," Jain said.

For the study, researchers collected thermophilic bacteria--those that thrive at temperatures between 106 and 262 degrees Farenheit--from hot springs and isolated the P450 enzyme.

They subjected the isolated enzymes to spectroscopy and neutron scattering, two techniques based in magnetism, to help illuminate the link between flexibility and thermal stability.

"There could be other enzymes that are as flexible at higher temperatures than P450, or that can become as flexible through simple mutations. If so, knowledge gained from future studies on them could then be used to target specific processes in the body, treat disease, or make new chemical products," said Lemmonds.

The evolution of barn swallows, a bird ubiquitous to bridges and sheds around the world, might be even more closely tied to humans than previously thought, according to new study from the University of Colorado Boulder.

The research, published this week in Molecular Ecology, offers preliminary insight suggesting that the barn swallow and its subspecies evolved alongside--but independently from--humans. These new results make it one of the only known species, in addition to microscopic organisms like bacteria or viruses, to have developed in such a way, upending previous assumptions that barn swallows evolved prior to human settlement.

"Humans could be a really big part of the story," said Rebecca Safran, a co-author of the study and an ecology and evolutionary biology (EBIO) associate professor at CU Boulder. "There's very few studies that can point to the exact influence of humans, and so here, this coincidence of human expansion and permanent settlement and the expansion of a group that relies really, really heavily on humans is compelling."

Barn swallows are found across the northern hemisphere and are characterized by their mud-cup nests that are built nearly exclusively on human-made structures. Despite their prevalence, however, not much is known about their evolutionary history, the timing of their expansion from northern Africa (where they originated) or how the six subspecies evolved so physically and behaviorally different yet remain almost genetically identical.

Previous studies published in the Proceedings of the Royal Society of London and Molecular Phylogenetics and Evolution looked into these questions and found that the different subspecies split early, well before human settlement.

This new study, however, gave the topic a fresh look by examining the whole genome of 168 barn swallows from the two sub-species farthest apart on an evolutionary scale: H. r. savignii in Egypt (a non-migratory species that lives along the Nile) and H. r. erythrogaster in North America (a species found throughout North America that migrates seasonally to South America).

These data--which are on the order of 100,000 times bigger than the previous dataset used--were then analyzed with more sophisticated computational resources and methods than previously available. This allowed researchers to get a more complete picture that places the timing of barn swallow differentiation or speciation (i.e., when the barn swallow subspecies separated) closer to that of when humans began to build structures and settlements.

"The previous studies were playing with the idea of potential impact on population sizes due to humans," said Chris Smith, a graduate student in EBIO and the Interdisciplinary Quantitative Biology program, and the study's lead author. "Our results suggest a much more substantial link with humans."

These new preliminary findings also suggest that this evolutionary link may have been forged through a "founder event," which is when a small number of individuals in a species take over a new environment and are able to expand their new population there thanks to an availability of resources and an absence of competitors. For barn swallows, this event may have occurred rapidly when they moved into a new, relatively empty environment: alongside humans.

"Everyone is always wondering how do you study speciation? It's been viewed as this long-term, million-year (process), but in barn swallows, we are not talking about differentiation within several thousands of years," said Safran. "Things are really unfolding rather rapidly."

Smith concurred: "It's interesting to study speciation in the beginning steps."

New research led by Lijun Song, associate professor of sociology at Vanderbilt University, and graduate student Phillip Pettis suggests that knowing people in high and diverse positions may be good or bad for your health. The culprit? Economic inequality.

Song studies the relationship between a person's health and the socioeconomic status of their social contacts--what's called "accessed" status. The idea is that we all have a personal network--consisting of family, friends, relatives, neighbors, coworkers, acquaintances and others--and the status of our social contacts can impact our lives through our relationships with them.

She and Pettis analyzed nationally representative data from comprehensive social surveys simultaneously taken in the United States, Taiwan and urban China to see whether a person's accessed status might impact whether they experienced a health issue in the previous year serious enough to keep them from participating in their daily routines for more than a week.

Accessed status can impact our health in interesting ways. Higher-status people tend to be healthier in general--they often are more knowledgeable and conscious about health, have more time and money to invest in a healthy lifestyle, experience less chronic stress and have greater access to medical care, among other positive things. Those are benefits that can extend to their social contacts, too--something called social capital theory.

"But we find that accessed status has a dark side, and we want to understand why," Song said. In two of the three societies she studied--the United States and China--being connected to higher- and diverse-status people was actually associated with more health disruptions, not less. That's an unexpected finding, and one that's not well understood.

To explain it, Song has proposed a new theory to explain the negative impacts of high accessed socioeconomic status on health, called social cost theory. Its main features include negative social comparison, receipt of detrimental resources and networking costs. An example of negative social comparison might be developing negative psychological feelings, such as anxiety or a sense of failure, and poor health habits, such as smoking, when comparing themselves with those in better-off situations, while an example of a detrimental resource might be unwanted intrusion in their affairs. A networking cost is simply the additional effort, such as time, money and energy, that goes into establishing and maintaining valuable high-status relationships.

Social burdens like these may make it harder for a sick person to get the support they need to get better faster.

So why does having higher- and diverse-status connections help in some societies and not in others? Economic inequality appears to play a role. Taiwan has relatively low economic inequality, and of the three societies studied, it is the only one that suggests the good outweighs the bad. The United States and China have much higher degrees of economic inequality, and show the reverse.

Song said it was important to note that the fact that China and Taiwan have different outcomes is interesting because they are both collectivistic societies, while the United States is an individualistic one. This suggests that future research should be cautious when applying collectivism-individualism models to questions of accessed status and health. Song and Pettis also caution that future longitudinal work is needed to understand the causal direction of and the direct mechanisms behind these effects. Additionally, future larger-scale comparative research is also needed to understand variations across different societies and cultures.