Culture

Better targeting at the district and neighborhood level could make anti-cholera efforts much more effective and dramatically reduce the burden of this disease, according to two new studies led by scientists at Johns Hopkins Bloomberg School of Public Health.

One of the teams of scientists developed a high-resolution map of cholera cases in most of Africa in a study to be published in The Lancet online on March 1. These maps show that while cholera is considered endemic in many African countries, most cases of the disease are concentrated in relatively few areas. Focusing anti-cholera efforts on these hotspots could reduce the region's annual burden of the disease by 50 percent by targeting fewer than five percent of districts in sub-Saharan Africa, the scientists estimate.

In a related study published on February 27 in PLoS Medicine, a team also led by Bloomberg School researchers modeled the rapid targeting of anti-cholera measures, including vaccination, to the areas immediately surrounding cholera victims' dwellings. They showed that this can be an efficient strategy to limit outbreaks, as an alternative or a complement to wider-scale interventions.

Mapping hotspots 

Cholera is widely underreported, with estimates of the actual global burden ranging up to 4 million cases and 143,000 deaths a year. There are 150,000 infections and thousands of deaths each year around the globe, according to the World Health Organization (WHO).

Much of this burden lies in sub-Saharan Africa, where frequent cholera outbreaks are a major source of social and economic disruption. Resources to fight cholera, including oral cholera vaccines (OCVs) and funds to build water and sanitation infrastructure, are limited in comparison with the population potentially at risk--including roughly a billion people in sub-Saharan Africa.

"To eliminate cholera as a public health problem we need to target control measures efficiently to those at highest risk," says Justin Lessler, an associate professor in the Bloomberg School's Department of Epidemiology and co-lead author of the Lancet study.

For the study, Lessler and colleagues gathered 279 separate datasets showing the locations of sub-Saharan Africa cholera cases in 37 countries from 2010 to 2016. The datasets came mostly from records of the WHO, Médecins Sans Frontières (Doctors Without Borders), African ministries of health, and other scientists' epidemiological studies. Datasets on two countries in the region, Eritrea and Djibouti, were not sufficiently complete to include.

The team mapped the region's reported cholera cases, which averaged 141,918 per year, to 20-square-kilometer grid cells. They defined the "high incidence" cells as those that averaged more than one case of cholera for every 1,000 residents during the study period. These hotspots, the researchers found, accounted for most of sub-Saharan Africa's cholera cases--yet they represented just a tiny proportion, roughly two percent, of the region's population. The scientists determined that effectively targeting cholera control efforts to only the worst of these hotspots would cut the region's cholera burden in half.

"In principle, we could do this by targeting only about 12 million people, or just 1.2 percent of the total study population, though targeting interventions at the grid-cell level is likely not a practical approach." Lessler says.

Targeting interventions based on actual political units, such as sub-provinces or districts rather than grid cells on a map, would be a more realistic approach. Although it would be less precise, it still would require the application of cholera control measures to only a small fraction of the study population, about 3.6 percent, the researchers found.

Lessler and colleagues now plan to extend their fine-scale cholera mapping efforts beyond Africa. "We'd like to develop an integrated global map of cholera cases and cholera risk, updated in near-real time," he says.

Targeting case areas

For the PLoS Medicine study, a team co-led by Andrew Azman, a research associate in the Bloomberg School's Department of Epidemiology, used detailed data from a 2011 cholera epidemic in Chad to make a computational model that could simulate realistic epidemics. The team, working with colleagues from École Polytechnique Fédérale de Lausanne, based these simulations on "fine-grained" data that showed the locations of victims' homes and timing of infection, allowing the researchers to see how it spread, from house to house, day by day.

They then used this to model a "case-area targeted intervention" strategy in which cholera-control measures are focused on people living in close proximity to victims.

"This strategy has been applied in some recent outbreaks, but there haven't been enough studies of whether it's effective and how to optimize it," Azman says.

The scientists modeled the use of OCVs, antibiotics, and point-of-use water treatment (POUWT) against simulated outbreaks. They found that even assuming realistic logistical delays, the early application of these combined interventions to individuals living in close proximity to cholera victims should be highly effective.

OCV appeared to be by far the most effective of the interventions. In the simulations, it reduced the duration of outbreaks by an average of 68 percent and the number of cases by 81 percent when applied within its optimal range--an area of 100-meter radius centered on each cholera case household. Adding POUWT and antibiotics improved that outcome only slightly. The modeling also showed that when applied in this case-area targeted manner, OCV can be more than 40 times more efficient at averting cholera cases than traditional mass-vaccination campaigns.

"Our findings suggest that case-area targeted interventions are much more resource-efficient and could play an important role in shortening the duration of outbreaks," Azman says.

The project was carried out in close collaboration with Médecins Sans Frontières, and Azman expects that MSF and other groups may consider using the case-area targeted approach in future cholera control efforts.

It's no new news that viruses cause cancer. For example, human papillomavirus (HPV) causes almost all of the more than 500,000 annual worldwide cases of cervical cancer. This makes sense: By driving the proliferation of infected cells, viruses speed manufacture of more viruses, but excessive cellular proliferation is also a hallmark of cancer. Now a University of Colorado Cancer Center review published in the journal Viruses explores another strategy that viruses use to ensure their own survival, also with the unfortunate byproduct of promoting cancer, namely the viral ability to manipulate the human immune system. This new understanding may help to increase the effectiveness of immune-based therapies against cancer.

"Ultimately, the virus is suppressing the immune system for its own benefit, and promoting the formation and proliferation of cancer cells may be just a side effect of that," says Sharon Kuss-Duerkop, PhD, research instructor working in the lab of CU Cancer Center investigator Dohun Pyeon, PhD.

Interestingly, while viruses certainly have the ability to edit human DNA - most obviously by inserting their own genetic code into DNA so that the new viruses are built alongside DNA replication - the review article explains that viruses do not necessarily turn off the immune system by editing genes. Instead, viruses mute the immune system by epigenetic regulation - instead of changing the actual code of genes, viruses change the degree to which genes are expressed.

They do this by a process called DNA methylation, which, very basically, is a way to silt over parts of the human genome to keep it from being read. In this case, viruses cause methylation of parts of the genome known as DNA promoter regions. Think of these promoter regions like on-off switches for next-door genes - when a promoter region is methylated, the switch is turned off and the gene it controls does not get read and expressed.

"You get lack of access by things that would be driving transcription," Kuss-Duerkop says. In other words, by methylating DNA promoter regions, viruses can turn off genes. But the virus itself doesn't do this - it's not as if viruses creep along a length of DNA spitting out methyl groups onto DNA promoters. Instead, in a Machiavellian twist, viruses recruit human proteins to methylate DNA and thus turn off important other bits of human DNA.

"Viruses encode particular proteins that can in some way modulate DNA methyltransferases," Kuss-Duerkop says, meaning that viruses can cause our own proteins to over-methylate our own DNA.

Of course, it makes sense that viruses would choose to turn off genes that the immune system needs to fight the virus, "like interferon-b, which is a highly anti-viral gene expressed in virtually all cell types; or genes that T cells need to recognize virus-infected cells," Kuss-Duerkop says.

The result is an immune system less able to fight the virus, and, if the virus causes cancer, a "microenvironment" near the tumor in which the immune system is suppressed. In fact, we see this in many cancers - tumors may specifically cloak themselves from the immune system, and they may also suppress the immune system more globally near the places they grow.

Sitting opposite these cancer-causing viruses and their ability to undercut the immune system are doctors and researchers who would like to recruit the immune system to attack cancer. Again: viruses turn down the immune system against the cancers they cause, and doctors would like to turn up the immune system against these same cancers.

And, in fact, these doctors and researchers are finding incredible success with this strategy; for example, PD-1 inhibitors remove this "cloak" that cancers use to hide from the immune system, and CAR-T cell therapies use specially engineered T-cells to seek cancer-specific proteins and destroy the cancer cells to which they are attached.

But challenges to immune-based therapies against cancer remain. Not least among which is the fact that while some patients respond to these therapies, others do not. The answer to increasing the effectiveness of immune therapies, or perhaps at least to choosing which patients are most likely to benefit from immune therapies, may lie in understanding the ways viruses (and cancers themselves) have evolved to evade the immune system.

Maybe if virus-related cancers have methylated DNA promoter regions of immune-related genes, the answer to increasing the effectiveness of immune-based therapies against cancer is to demethylate these genes.

"You don't want to just turn down methylation globally, which would result in over-activation of all genes in the cell, but demethylating some of these gene promoter regions selectively could revive an immune system muted by cancer-causing viruses," Kuss-Duerkop says.

"Ultimately viruses are causing these tumors to form and are further manipulating the immune system to allow tumors to keep growing," Kuss-Duerkop says. "But these same mechanisms may be key in combating tumors with immune-based therapies or in keeping cancer from developing in the first place."

Research led by The University of Notre Dame Australia, NICM and Western Sydney University, shows antenatal education not only reduces the rates of medical interventions during childbirth, but can save the healthcare system up to AU$97 million per year.

The Australian-first research found that an effective childbirth education programme - which significantly reduced the incidence of caesarean births - could save an average of AU$808 per woman.

Lead author, Dr Kate Levett says applied to the 120,000 first time mothers who give birth annually in Australia, the potential saving for hospitals, government and private health insurers is significant and is likely to be an underestimate of the actual amount of medical resources saved.

"Most of the medical savings in the model come from the reduction in rate of uncomplicated caesarean section in the women allocated to the 2-day antenatal programme, Complementary Therapies for Labour and Birth (CTLB)," said Dr Levett, Research Fellow at The University of Notre Dame Australia and Adjunct Fellow at NICM.

"Our previous research showed that after taking the CTLB course, approximately 82 per cent of women, who were first time mothers, experienced a vaginal birth, as opposed to a caesarean section.

"With the global emphasis on reducing caesarean section rates and the budgetary constraints faced by maternity providers, the potential benefits of this intervention may be significant from both a clinical and an economical perspective," Dr Levett said.

Published online in the medical journal BMJ Open, the latest study is part of an ongoing collaborative investigation into the high rates, and costs of medical intervention that women experience during childbirth.

"We have a strong international collaborative team with NICM, the School of Nursing and Midwifery, and the Translational Health Research Institute at Western Sydney University, The University of Central Lancashire UK, and Health Economist, Associate Professor Federico Girosi at Capital Markets CRC Australia and Western Sydney University, who designed the analysis," said Dr Levett.

The researchers say the use of AR-DRG codes provides a simple way to conduct cost analyses for particular interventions, as well as enabling healthcare commissioners and providers around the world to make informed choices about the added value of a proposed intervention.

Frequent medical interventions during childbirth are problematic as they commonly result in instrumental birth or caesarean section at a high cost, both mentally and financially.

The researchers' latest findings look specifically at the cost implications of the CLTB intervention, and propose that savings generated from reduced medical interventions, specifically caesarean section, could be used to resource effective evidence-based antenatal education for women.

Dr Levett said antenatal education programmes like CTLB can reduce the stress of childbirth and save valuable hospital resources.

"Previous research has shown the antenatal CTLB programme significantly reduces epidural use, as well as reducing a range of other clinical interventions that have important adverse consequences, including caesarean section, if overused in healthy women and babies," Dr Levett said.

While wider national and international implementation of the pilot clinical trial is recommended to confirm results in a broader population and examine issues of generalisability, the researchers say the positive savings could lead to a reduction in birth-related healthcare costs of approximately nine per cent.

Philadelphia, March 1, 2018 - Marijuana is the most commonly used illicit drug in the United States, with an increasing trend of use among middle-aged and older individuals. However, potential health effects of marijuana use in the general population have not been extensively studied, and little is known about potential effects on kidney function. According to a new cross-sectional study of adults aged 18-59 in the US, there is no association between current or previous marijuana use and kidney function. The results are reported in The American Journal of Medicine.

Marijuana use among people aged 12 years or older in the US has increased from 7.5 percent to 8.3 percent from 2013 to 2015. From 2002 to 2015, the increase in percentage of adult users 26 years or older is even greater than the increase among those aged 18 to 25 years during the same period. Health effects of acute and chronic marijuana use remain controversial and the US Food and Drug Administration (FDA) has not officially approved marijuana as a medicine, nor has it been extensively studied within the general population. Little is known about its potential effects on kidney function.

Investigators analyzed a nationally representative sample of nearly 14,000 predominantly healthy adults aged 18-59 years living in the US who participated in the National Health and Nutrition Examination Survey from 2007 to 2014. Participants used an audio computer-assisted self-interview system to answer several questions. Questionnaires were administered at a mobile examination center. Participants were classified as never users, past users, and current users of marijuana. Nearly 5,500 users said they had smoked marijuana at least once, but not in the past 30 days, and over 2,000 users had smoked marijuana at least once within the last 30 days. Serum creatinine concentration was measured after blood collection at the mobile examination center.

The investigators did not find any association between current or past marijuana use and impaired kidney function. There was no statistically significant association between history of marijuana use and the likelihood of developing stage 2 or greater chronic kidney disease. Likewise, they did not observe a statistically significant association between the history of marijuana use and the incidence of microalbuminuria, a moderate increase in the level of urine albumin and a marker of kidney disease.

"Our research provides some reassuring evidence suggesting that there is no determinantal effect of infrequent, relatively light use of marijuana on kidney function among healthy adults under age 60," commented lead investigator Murray A. Mittleman, MD, DrPH, Professor of Epidemiology at the Harvard T.H. Chan School of Public Health, Associate Professor of Medicine at Harvard Medical School, and a practicing preventive cardiologist at Beth Israel Deaconess Medical Center. "However, our research does not address heavy users, the elderly, or those with preexisting chronic kidney disease. Research is needed to evaluate the impact of marijuana use in adults 60 and over, and among those with existing or at risk of developing kidney disease."

Under US Federal law it is illegal to possess, use, buy, sell, or cultivate marijuana, although it is legal in some US states. As of January 2018, medical marijuana is legal in 30 states and the District of Columbia (DC); in eight states and DC, it is also legal for recreational use. Other states have taken steps to decriminalize marijuana to some degree.

Researchers from Nationwide Children's Hospital have shown that omega fatty acid supplements may improve autism spectrum disorder symptoms in toddlers who were born very preterm (more than 11 weeks early). The study was published recently in the Journal of Nutrition.

"The trial had two goals. First, we wanted to confirm the feasibility of a large study of toddlers born very preterm and exhibiting symptoms often seen with ASD. Second, we wanted to see what the effects of omega fatty acids would be on parent-reported ASD symptoms and related behaviors," says Sarah Keim, Ph.D., lead author on the study and principal investigator in the Center for Biobehavioral Health in The Research Institute at Nationwide Children's.

Dr. Keim and her team conducted a study where 31 toddlers who were born prematurely participated. For 3 months, half of them took a daily dietary supplement that contained a special combination of omega-3 and omega-6 fatty acids, and the other half took a placebo, although families were unaware of which they received to make the study rigorous.

The group that took the daily omega fatty acid supplement exhibited a greater reduction in ASD symptoms than those who took the placebo, according to ratings provided by the children's parents.

"We found clinically significant improvements in ASD symptoms in the treatment group, although the benefits were confined to one measure we used," explains Dr. Keim. "We need to do a larger trial to further understand the potential impacts on a larger group of children."

The researchers suggest that observed benefits of omega fatty acid supplementation could be due to the role of these nutrients in inflammation in the body. ASD is generally considered a neuroinflammatory condition, and influencing inflammation through nutritional supplementation could improve behaviors in children with ASD symptoms.

Researchers hope that by giving omega fatty acids to children early when they first show symptoms and the brain is still actively developing may help them long-term.

"Currently, no medications are available to help children born prematurely with the developmental delays and behavior problems they often experience. For very young children, the medications that physicians sometimes try tend to have many side effects. And we don't know what effect those medications have on brains that are still developing," says Dr. Keim. "If using omega fatty acid supplementation helps, it would have a really huge impact for these kids."

Dr. Keim and her team plan to expand the work in a full-scale trial in the future. They recently received a grant from the National Institutes of Health to study the effect of omega fatty acids in children ages 2-6 year who have ASD.

Atlanta, GA - New research shows when it comes to successfully engaging and including minorities in the workforce and schools, organizations need to focus on inclusion. Several social psychology researchers will share details of their results at the SPSP Annual Convention on March 2nd.

"Institutions tend to overemphasize numerical diversity to the exclusion of inclusion" says Erika Hall (Emory University), one of the presenters and co-chair of the symposium.

Inclusive Businesses

An organization can be diverse in numbers, yet minorities may still report feelings of discrimination. How does one go beyond this "numerical" diversity to true feelings of inclusion? Erika Hall surveyed 486 minority business owners from the National Minority Supplier Diversity Council to determine what might have an effect. Her research showed a high combination of authenticity coupled with increased levels of perceived racial diversity significantly decreased major experiences of discrimination (B = -.17, p

"As a minority, part of the benefit of having people around you that look like you is that you may feel more comfortable enacting behaviors or discussing topics that are specific to your culture, and you may feel that you belong because other people like you are a part of the organizational culture."

These benefits are lost however, according to Hall, "if institutional constraints restrict you from bringing your whole, true self to work and dictate that you don't belong, numerical diversity will become obsolete."

Organizational attempts to be inclusive can lead to feelings of exclusions for other groups.

Tessa Dover (Portland State University) looked at the affect pro-diversity messages have for those in high status groups, in this study, white men. In a series of experiments, she and colleagues show that whites who imagined seeking a job were negatively affected by pro-diversity messages and performed more poorly in potential job interviews. They expressed concerns of being treated unfairly, and of anti-white discrimination.

Inclusive Schools

Tiffany Brannon's (University of California, Los Angeles) research provides evidence that school settings can affirm identity among members of negatively stereotyped groups-- by, for instance, incorporating diverse cultural ideas and practices within academic courses or extracurricular activities-- and, in turn, afford an increased sense of inclusion.

Analyzing longitudinal datasets (N= 2,926 and N=1,255) of African American and Latino American college students Brannon's research demonstrates that such efforts to affirm identity is related to benefits among members of negatively stereotyped groups including better problem solving, increased task persistence, higher GPAs, and more positive health and well-being outcomes.

MarYam Hamedani (Stanford University) will discuss work on how difference-education interventions can successfully educate students about social difference and improve first-generation college students' grades.

Today's increasingly diverse and divided world frequently requires the ability to understand and navigate across social difference. Hamedani and colleagues propose that interventions that teach students about social difference can not only foster students' intergroup skills, but can also help disadvantaged students succeed in school.

"This study supports a growing body of work demonstrating that teaching students a contextual understanding of difference--i.e., recognizing that people's differences come from participating in and adapting to diverse sociocultural contexts--can be leveraged to foster student success and close achievement gaps," summarizes Hamedani.

The Moving Beyond Diversity to Inclusion: Building Inclusive Schools and Workplaces symposium takes place March 2, at 12:45 p.m. ET. The session is one of over 80 scientifc sessions at the Society for Personality and Social Psychology Annual Convention in Atlanta, Georgia.

The phenomenon of women discriminating against other women in the workplace -- particularly as they rise in seniority -- has long been documented as the "queen bee syndrome." As women have increased their ranks in the workplace, most will admit to experiencing rude behavior and incivility.

Who is at fault for dishing out these mildly deviant behaviors? Has the syndrome grown more pervasive?

"Studies show women report more incivility experiences overall than men, but we wanted to find out who was targeting women with rude remarks," said Allison Gabriel, assistant professor of management and organizations in the University of Arizona's Eller College of Management.

Gabriel and her co-authors set out to answer that question across three studies. Men and women who were employed full time answered questions about the incivility they experienced at work during the last month. The questions were about co-workers who put them down or were condescending, made demeaning or derogatory remarks, ignored them in a meeting or addressed them in unprofessional terms. Each set of questions was answered twice, once for male co-workers and once for female co-workers.

"Across the three studies, we found consistent evidence that women reported higher levels of incivility from other women than their male counterparts," Gabriel said. "In other words, women are ruder to each other than they are to men, or than men are to women.

"This isn't to say men were off the hook or they weren't engaging in these behaviors," she noted. "But when we compared the average levels of incivility reported, female-instigated incivility was reported more often than male-instigated incivility by women in our three studies."

Participants also were asked to complete trait inventories of their personalities and behaviors to determine if there were any factors that contributed to women being treated uncivilly. The research showed that women who defied gender norms by being more assertive and dominant at work were more likely to be targeted by their female counterparts, compared to women who exhibited fewer of those traits.

The researchers also found that when men acted assertive and warm -- in general, not considered the norm for male behavior -- they reported lower incivility from their male counterparts. This suggests men actually get a social credit for partially deviating from their gender stereotypes, a benefit that women are not afforded.

Gabriel, whose co-authors are Marcus Butts from Southern Methodist University, Zhenyu Yuan of the University of Iowa, Rebecca Rosen of Indiana University and Michael Sliter of First Person Consulting, said the research is important not only from the standpoint of individual employee health but also in terms of organizational management.

Evidence emerged in the three studies that companies may face a greater risk of losing female employees who experience female-instigated incivility, as they reported less satisfaction at work and increased intentions to quit their current jobs in response to these unpleasant experiences. Paired with estimates that incivility can cost organizations an estimated $14,000 per employee, this presents a problem for organizations.

Gabriel noted that the findings are an opportunity for companies to re-evaluate their cultures and how they address this issue.

"Companies should be asking, 'What kinds of interventions can be put in place to really shift the narrative and reframe it?'" Gabriel said. "Making workplace interactions more positive and supportive for employees can go a long way toward creating a more positive, healthier environment that helps sustain the company in the long run. Organizations should make sure they also send signals that the ideas and opinions of all employees are valued, and that supporting others is crucial for business success -- that is, acting assertively should not be viewed negatively, but as a positive way for employees to voice concerns and speak up."

Calcium supplements, taken with or without vitamin D, may increase the risk of small growths in the large bowel (colon) called polyps, suggest results from a large US trial published online in the journal Gut.

The researchers say further studies are recommended to confirm these results - and any possible risks must be weighed against the benefits of supplementation. But given that calcium supplements are taken by millions of people around the world, the findings may have important implications for bowel cancer screening and prevention.

Polyps are small growths in the lower part of the large bowel. They are non-cancerous, but some could eventually turn into cancer if they are not removed.

Polyps come in different shapes and sizes, and this study specifically focused on the risk of serrated polyps, which are less common than conventional "adenomatous" polyps, but likely have the same risk of developing into cancer. Some studies have suggested that calcium and vitamin D may protect against colon polyps, but results have been mixed.

So to investigate further, a team of US-based researchers set out to determine whether taking daily calcium and vitamin D supplements reduce the risk of serrated polyps.

They analysed findings from a large US trial involving over 2,000 patients aged between 45 and 75 who had a history of polyps and were due to have a follow-up test (colonoscopsy) in 3 to 5 years.

Patients were excluded if they had a family history of bowel cancer, inflammatory bowel disease, or other serious health conditions - and several factors were taken into account at the start of the study, including sex, diet, weight (BMI), and use of anti-inflammatory drugs.

The remaining patients were randomly split into groups to receive either daily calcium supplements, daily vitamin D supplements, both or neither for 3 or 5 years (treatment phase) until their colonoscopsy.

Effects 3 to 5 years after treatment ended (observational phase) were also recorded.

During the treatment phase, there was no effect of either calcium or vitamin D on cases of serrated polyps. However, during the later observational phase (6-10 years after treatment began), the researchers found increased risks of serrated polyps among patients taking calcium alone and among those taking a combination of calcium and vitamin D.

There was evidence that women and smokers were at higher risk when exposed to calcium supplements, but no association was found between vitamin D alone and the risk of serrated polyps. The results also suggest an association with calcium supplements only, not dietary calcium.

Strengths of the study include its randomised design and large sample size, say the authors. However, they point out that findings are derived from a secondary analysis of a trial and it is possible that some results from these analyses were due to chance.

Further studies are recommended to confirm these results, say the authors, but if calcium and its combination with vitamin D are truly associated with an increased risk of serrated polyps, "this has important public health implications," they conclude.

In the meantime, they suggest that patients with a history of pre-cancerous serrated polyps, especially women and smokers, may wish to avoid vitamin D and calcium supplementation.

JUPITER, FL - March 1, 2018 - Scientists on the Florida campus of The Scripps Research Institute (TSRI) have discovered a new target for treating major depressive disorder, a disease that affects more than 16 million American adults. Their research shows that individuals with high levels of an enigmatic receptor called GPR158 may be more susceptible to depression following chronic stress.

"The next step in this process is to come up with a drug that can target this receptor," says Kirill Martemyanov, PhD, co-chair of the TSRI Department of Neuroscience and senior author of the new study, published recently in the journal eLife.

The researchers say there is an urgent need for new drug targets in major depressive disorder. Current pharmacological treatments for depression can take a month to start working--and they don't work in all patients.

"We need to know what is happening in the brain so that we can develop more efficient therapies," says Cesare Orlandi, PhD, senior research associate at TSRI and co-first author of the study.

The researchers zeroed in on GPR158 as a player in depression after discovering that the protein is elevated in people with major depressive disorder. To better understand GPR158's role, the scientists studied male and female mice with and without GPR158 receptors.

Behavioral tests revealed that both male and female mice with elevated GPR158 show signs of depression following chronic stress. On the flip side, suppression of GPR158 protects mice from developing depressive-like behaviors and make them resilient to stress.

Next, the researchers examined why GPR158 has these effects on depression. The team demonstrated that GPR158 affects key signaling pathways involved in mood regulation in the region of the brain called prefrontal cortex, though the researchers emphasized that the exact mechanisms remain to be established.

Martemyanov explains that GPR158 is a so-called "orphan receptor" (which gets its name because its binding partner/partners are unknown) with a poorly understood biology and mechanism of action. GPR158 appears to work downstream from other important brain systems, such as the GABA, a major player in the brain's inhibitory control and adrenergic system involved in stress effects.

"This is really new biology and we still need to learn a lot," says Martemyanov.

The study also offers a potential clue to why some people are more susceptible to mental illness. Because mice without GPR158 don't alter their behavior after chronic stress, the researchers concluded these mice were naturally more resilient against depression. Their genetics, or gene expression, offer a layer of protection.

Laurie Sutton, PhD, a research associate at TSRI and co-first author of the study, says this finding matches what doctors have noticed in people who have experienced chronic stress. "There's always a small population that is resilient--they don't show the depressive phenotype," says Sutton.

As the search goes on for additional targets for depression, Martemyanov says scientists areincreasingly using new tools in genome analysis to identify orphan receptors like GPR158. "Those are the untapped biology of our genomes, with significant potential for development of innovative therapeutics," he says.

WASHINGTON, DC (March 1, 2018)--A new report published today in the Journal of Adolescent Health says that the recent changes in U.S. immigration policy have triggered serious psychological distress for many Latino parents, including those living in the United States legally.

The study, by researchers at Milken Institute School of Public Health (Milken Institute SPH) at the George Washington University (GW), is one of the first to look at how the 2017 U.S. immigration policies are affecting Latino parents--and by extension their teenage children.

"A substantial proportion of Latino parents reported that they are avoiding authorities, warning their children to change their routines and worrying about the future due to recent U.S. immigration policies and news," said lead author Kathleen Roche, MSW, PhD, an associate professor of prevention and community health at Milken Institute SPH. "Parents experiencing these kinds of immigration-related consequences also appear to be at a very high risk of anxiety, depression, and other forms of distress."

Roche and her colleagues studied 213 Latino, mostly Central American, parents of adolescent children recruited from a suburb of a large mid-Atlantic city. Although some parents in the study were undocumented, more than two-thirds were living in the US legally, whether as a citizen, permanent resident, or under temporary protected status.

The researchers asked the parents a series of questions to find out how U.S. immigration actions and news had affected them in recent months. Here are some key findings from the survey:

A substantial proportion of US Latino parents reported adverse emotional and behavioral consequences from recent immigration actions and news. For example, 64 percent said that they very often or always worried about family members getting separated.

Nearly 40 percent of parents said they frequently avoided getting medical care, help from police, or support from social services because of immigration actions and news;

Almost half of the parents reported that recent immigration events had led them to very often or always warn their teenagers to stay away from authorities and to change their behaviors such as where the youth hang out.

In addition, the researchers used a standard questionnaire to assess symptoms of depression, anxiety and other mental health problems.

Parents who frequently experienced worries or changes in behavior due to immigration news and policies had at least a 300 percent increase in the odds of high psychological distress, including symptoms of clinical anxiety and depression, Roche said.
"Such high levels of distress among parents raise concerns about immigration impacts on the entire family, including among teenagers," Roche says. "Studies show that adolescents whose parents are anxious or depressed are at elevated risk of doing poorly in school, adopting risky behaviors, and developing lifelong health and mental health problems."

The findings, which come from a small survey, must be verified by other researchers, Roche adds. However, the association between U.S. immigration actions and psychological distress in this study held true after controlling for education, residency status, gender and other factors.

Previous research suggests that a parent's fear, anxiety or depression can spill over to affect the entire family, and especially teenagers.

Virtually all of the Latino adolescents whose parents were in this study were either U.S. citizens or protected under Deferred Action Childhood Arrivals or DACA, points out study co-author Elizabeth Vaquera, PhD, Director of the Cisneros Hispanic Leadership Institute at GW. "Thus, even though Latino adolescents have grown up in the United States and are here legally they still face serious risks to their health and well-being," she said.

San Francisco, CA -- March 1, 2018 -- Some organisms have a remarkable capacity for regenerating tissue. If a fish or salamander suffers heart damage, for instance, their cells are able to divide and successfully repair the injured organ. Imagine if you could do the same.

In the embryo, human heart cells can divide and multiply, allowing the heart to grow and develop. The problem is that, right after birth, cardiomyocytes (heart muscle cells) lose their ability to divide. The same is true for many other human cells, including those of the brain, spinal cord, and pancreas.

"Because so many adult cells can't divide, your body can't replace cells that are lost, which causes disease," explained Deepak Srivastava, MD, president of the Gladstone Institutes and senior investigator. "If we could find a way to get these cells to divide again, we could regenerate a number of tissues."

For decades, the scientific community has been trying to do just that, with limited success. Until now, attempts have been ineffective and poorly reproducible.

In a new study published in the scientific journal Cell, Srivastava and his team finally reached this long-sought goal. They developed the first efficient and stable method to make adult cardiomyocytes divide and repair hearts damaged by heart attacks, at least in animal models.

Over 24 million people worldwide suffer from heart failure, with few treatment options available other than heart transplants for end-stage patients. The potential to create new muscle cells through cell division, much like a salamander does, could offer new hope to the millions living with damaged hearts.

Unlocking an Adult Cell's Potential to Multiply

Srivastava and his team identified four genes involved in controlling the cycle of cell division. They found that when combined--and only when combined--these genes cause mature cardiomyocytes to re-enter the cell cycle. This results in the cells dividing and rapidly reproducing.

"We discovered that when we increased the function of these four genes at the same time, the adult cells were able to start dividing again and regenerated heart tissue," said Tamer Mohamed, scientist at Tenaya Therapeutics and former postdoctoral scholar in Srivastava's laboratory, who is first author of the study. "We also showed that, after heart failure, this combination of genes significantly improves cardiac function."

The scientists tested their technique in animal models and cardiomyocytes derived from human stem cells. They used a rigorous approach to track whether the adult cells were truly dividing in the heart by genetically marking newly divided cells with a specific color that could be easily monitored. They demonstrated that 15-20 percent of the cardiomyocytes were able to divide and stay alive due to the four-gene cocktail.

"This represents a considerable increase in efficiency and reliability when compared to previous studies that could only cause up to 1 percent of cells to divide," said Srivastava, who is also a professor at UC San Francisco. "Of course, in human organs, the delivery of genes would have to be controlled carefully, since excessive or unwanted cell division could cause tumors."

To further simplify their technique, the team looked for ways to reduce the number of genes needed for cell division while maintaining efficiency. They found they could achieve the same results by replacing two of the four genes with two drug-like molecules.

Regenerating Multiple Human Tissues

The researchers believe that their technique could also be used to coax other types of adult cells to divide again, given that the four genes they used are not unique to the heart.

"Heart cells were particularly challenging because when they exit the cell cycle after birth, their state is really locked down--which might explain why we don't get heart tumors," said Srivastava. "Now that we know our method is successful with this difficult cell type, we think it could be used to unlock other cells' potential to divide, including nerve cells, pancreatic cells, hair cells in the ear, and retinal cells."

This could lead to a powerful regenerative approach to treat not only heart failure, but also brain damage, diabetes, hearing loss, and blindness. And one day, the human might just outperform the salamander.

Jumping robot spiders and swarms of robotic bees sounds like the stuff of science fiction, but researchers at The University of Manchester are already working on such projects and aiming to lead the world in micro robotics.

But what will these kinds of robots be used for and is it something we should be worried? Dr Mostafa Nabawy is the Microsystems Research Theme Leader at The University of Manchester's School of Mechanical, Aerospace and Civil Engineering. He is presenting some of his research, "Spiders Attack: The rise of bioinspired microrobots" at Manchester's Industry 4.0 Summit on Thursday 1 March.

Here Dr Nabawy explains why micro robots really aren't anything to worry about and, instead, could be the revolution in robotics that spearheads the next generation in manufacturing technology:

'For our robotic spiders research we are looking at a specific species of jumping spider called Phidippus regius. We have trained it to jump different distances and heights, recording the spider's every movement in extreme detail through high resolution cameras which can be slowed down.

'We are now using this bio-mechanical data to model robots that can perform with the same abilities. With this extensive dataset we have already started developing prototype robots that can mimic these biomechanical movements and jump several centimetres.'

Why jumping spiders you ask? Unlike humans, our spiders can jump up to six-times longer than their own body length from a standing start. In comparison, the maximum a human can jump is just one and half times. Dr Nabawy says if we can perfect the way spiders jump in robots they can be used for a variety of different purposes in complex engineering and manufacturing and can be deployed in unknown environments to execute different missions.

Dr Nabawy's research and background is in aerodynamics, aircraft design, and the modelling of engineering systems. But he is now combining this expertise with bio-inspired flying and jumping technologies, including flying robot bees.

He added: 'The ultimate aim is to create a robot bee that can fly independently and we're quite a long way into that project. But there are also many different opportunities for brilliant science and engineering outcomes along the way so it is a very exciting process.

'We're aiming to create the world's first robot bee that can fly unaided and unaccompanied. These technologies can also be used for many different applications, including improving the current aerodynamic performances of aircraft.

'Or, imagine if the current trend of a declining bee population continues, swarms of robot bees pollinating crops and flowers could become a reality. Whilst this may sound like something out of a transformers film this is our ultimate aim. But don't worry we are someway off swarms of flying mechanical bees and armies of mechanical spider robots.'

The Industry 4.0 summit is looking at the future of the manufacturing industry, but will also look at topics ranging from Brexit and the Northern Powerhouse to skills shortages, cyber-security and blue skies technology.

UNIVERSITY PARK, Pa. -- Prenatal exposure to male hormones influences which activities girls are interested and engage in, but the effects of those hormones don't extend to gender identity or who they socialize with, according to Penn State researchers.

The researchers explored how prenatal exposure to androgens -- hormones that are typically higher in males than in females -- affected whether girls played more often with boys or girls.

They found that androgen exposure was not associated with girls spending more or less time in activities with other girls, but it was associated with an increased interest and more time spent in activities that have traditionally been thought of as masculine, like building things or playing or watching sports.

Sheri Berenbaum, professor of psychology, Penn State, said the results -- published in the Archives of Sexual Behavior -- support the idea that gender development is a complex process that does not solely rely on either biological or social factors.

"People used to think -- and some still do -- that gender development and behavior is based either on a person's biology or social environment," Berenbaum said. "But I think people now realize that it's both, and the question is how these forces work together. So we're trying to delve into how hormones and socialization both affect gender development."

According to the researchers, children typically begin spending more time socializing with children of their own gender in early childhood, referred to as "sex segregation." Berenbaum said this tendency has been hypothesized to result from such factors as gender identity and personal characteristics.

Berenbaum said the study was an opportunity for researchers from different backgrounds -- some who look at gender from a biological perspective and some who view it from a socialization perspective -- to work together to see how these perspectives merge.

The researchers found they could examine the effects of hormones on sex segregation by studying girls with classical and non-classical congenital adrenal hyperplasia (CAH). Girls with classical CAH are exposed to excess levels of androgens prenatally, while girls with non-classical CAH are not.

The researchers recruited 54 girls between the ages of 10 and 13 with CAH -- 40 with classical CAH and 14 with non-classical CAH. They interviewed the girls about their activity interests, gender identity and attitudes about gender roles, among other things. The researchers also called the girls on seven evenings over the next two to four weeks to ask them how much time they spent on particular activities that day, and who they spent their time with.

"Our hypothesis was that the girls with classical CAH, the ones with prenatal androgen exposure, would spend more time with boys," Berenbaum said. "But because we also knew that most of these girls identified as girls, we thought that they might spend more of their time with girls. As it turned out, they did not spend more time with boys."

The researchers found that there was no significant association between androgen exposure and girls' time spent with either boys or girls. But, they did find that girls with classical CAH -- those with prenatal androgen exposure -- spent more time in male-typical activities and less time in female-typical activities.

Additionally, they found that the majority of girls with classical CAH identified as girls and had typical attitudes about gender, which could contribute to their interacting mainly with other girls, a pattern that suggests that hormones may not have an effect on gender identity and attitudes, according to Berenbaum.

Susan McHale, distinguished professor of human development and family studies, Penn State, agreed that the results suggest that gender development and segregation result from both biological and social influences.

"A number of theories have been proposed to explain sex segregation, most of which focus on socialization," McHale said. "Findings from this study suggest that gender development is more complex than a simple matter of socialization and are consistent with the idea that nature and nurture interact to explain gender development, and they illuminate one such interactive process."

In an additional paper recently published in Child Development Perspectives, Berenbaum discussed the complexity of androgen effects on behavior and the value of studying girls with CAH. She said that in the future, she would like to continue studying the brain structure of girls with CAH and further explore how biology and socialization work together to influence development.

"Behavior is complex, but some people resist the idea that biology influences behavior because they think it means that behavior is predetermined and cannot be changed," Berenbaum said. "But that's not true. Biological influences don't mean everything is fixed when you're born. Behaviors that are influenced by hormones and other biological processes can still be changed by the environment."

New Haven, Conn. -- People with stage III colon cancer who regularly eat nuts are at significantly lower risk of cancer recurrence and mortality than those who don't, according to a new, large study led by researchers at Yale Cancer Center.

The findings were published today in the Journal of Clinical Oncology.

The study followed 826 participants in a clinical trial for a median of 6.5 years after they were treated with surgery and chemotherapy. Those who regularly consumed at least two, one-ounce servings of nuts each week demonstrated a 42% improvement in disease-free survival and a 57% improvement in overall survival.

"Further analysis of this cohort revealed that disease-free survival increased by 46% among the subgroup of nut consumers who ate tree nuts rather than peanuts," said Charles S. Fuchs, M.D., M.P.H., director of Yale Cancer Center and senior author of the study. Tree nuts include almonds, walnuts, hazelnuts, cashews, and pecans, among others. In contrast, peanuts are actually in the legumes family of foods.

"These findings are in keeping with several other observational studies that indicate that a slew of healthy behaviors, including increased physical activity, keeping a healthy weight, and lower intake of sugar and sweetened beverages, improve colon cancer outcomes," said Temidayo Fadelu, M.D., a postdoctoral fellow at Dana-Farber Cancer Institute and lead author of the paper. "The results highlight the importance of emphasizing dietary and life-style factors in colon cancer survivorship."

Additionally, the researchers emphasized, the study highlighted connections between biological mechanisms that worsen disease not just in colon cancer but in certain chronic illnesses such as type 2 diabetes.

Many previous studies have reported that nuts, among other health benefits, may help to reduce insulin resistance, a condition in which the body has difficulty processing the insulin hormone. Insulin resistance leads to unhealthy levels of sugar in the blood and is often a predecessor to type 2 diabetes and related illnesses.

Earlier research among patients with colon cancer has revealed worse outcomes among those with lifestyle factors that heighten insulin resistance, such as obesity, lack of exercise, and a diet with high levels of carbohydrates that quickly raise levels of blood sugar.

"These studies support the hypothesis that behaviors that make you less insulin resistant, including eating nuts, seem to improve outcomes in colon cancer," Fuchs said. "However, we don't know yet what exactly about nuts is beneficial."

Nuts also might play a positive role by satisfying hunger with less intake of carbohydrates or other foods associated with poor outcomes, Fuchs noted.

Patients may not be eating nuts due to concerns about the high fat content. For example, a one-ounce serving of about 24 almonds holds about 200 calories, including 14 grams of fat. "People ask me if increasing nut consumption will lead to obesity, which leads to worse outcomes," he said. "But what's really interesting is that in our studies, and across the scientific literature in general, regular consumers of nuts tend to be leaner."

Dietary changes can make a difference. An earlier analysis of diets in the same patient cohort by Fuchs and his colleagues found a significant link between coffee consumption and reduced recurrence and mortality in colon cancer.

When Fuchs advises his patients about lifestyle choices, "first and foremost I talk about avoiding obesity, exercising regularly and staying away from a high-carbohydrate diet," he said. "Then we talk about things like coffee and nuts. If you like coffee or nuts, enjoy them, and if you don't, there are many other helpful steps you can take."

"Overall, we are working to apply the same rigorous science to the understanding of diet and lifestyles in the colon cancer patient population that we apply to defining new drugs," Fuchs said.

February 28, 2018 - In patients undergoing reconstructive surgery of the face, treatment with botulinum toxin A (BTX-A, or 'Botox') can improve the final appearance of surgical scars, reports a clinical trial in the March issue of Plastic and Reconstructive Surgery®, the official medical journal of the American Society of Plastic Surgeons (ASPS).

"This study demonstrates that early post-surgical botulinum toxin injections can produce better, narrower, and flatter facial surgical scars," according to the study by XiaoXi Lin, MD, PhD, and colleagues of Shanghai Jiao Tong University School of Medicine. The results add to the growing list of clinical applications for BTX-A--beyond its cosmetic use in treating facial lines and wrinkles.

Early Botox Treatment Improves Final Appearance in 'Split-Scar' Study

The study included 16 patients undergoing facial plastic and reconstructive surgery at the authors' department over a four-month period. The patients averaged 12 years of age. Most were undergoing surgery for some type of disfiguring facial birthmark, such as a melanocytic nevus or port wine stain.

In each patient, half of the facial scar was randomly assigned to treatment with BTX-A or inactive saline (placebo) solution, injected immediately at the end of surgery. Six months later, independent plastic surgeons made measurements and rated the appearance of both sides of the scar. The scars averaged 6.74 centimeters in length, with a range of three to 16 centimeters (about one to six inches). The study included follow-up data in 14 patients.

By several measures, the final appearance of the scar was significantly better on the half treated with BTX-A. On a 0- to 10-point scale (with 0 being worst and 10 being best), the surgeon's ratings for overall scar appearance averaged 5.76 on the half treated with BTX-A versus 4.97 on the placebo-treated half.

The BTX-A-treated sides were also lower and narrower than then comparison sides. Other scar characteristics (color, pliability, and vascularity) were not significantly different.

Injection of BTX-A--best known by the brand name Botox--is widely used for treatment of facial lines and wrinkles. It is the most common cosmetic procedure in the United States, with about 7 million BTX-A injection procedures performed in 2016, according to ASPS statistics. In recent years, BTX-A has also been effectively used to treat a wide range of non-cosmetic problems as well.

How does BTX-A affect the process of scar formation? "Temporary muscular paralysis induced by BTX-A could decrease movement and stress around a healing wound," Dr. Lin and coauthors speculate. "This relief of tension may help prevent facial scar widening, hypertrophy and hyperpigmentation." They cite previous studies suggesting that BTX-A might also inhibit certain cells (fibroblasts) and mediators involved in scar.

The authors note some important limitations of their preliminary study, particularly the small number of patients included. They propose further studies comparing the effects of BTX-A on surgical scars with different injection techniques and in different locations on the face.

In a featured video on the Plastic and Reconstructive Surgery website, Editor-in-Chief Rod J. Rohrich, MD, notes that previous studies have reported the use of BTX-A to treat a variety of problems, "including chronic migraines, twitching eyelids, extreme sweating, crossed eyes, and more." He adds, "While more research is needed, this new [study] may demonstrate that early post-surgical injections of botulinum toxin can produce better, smaller, and flatter facial surgical scars."