February 24, 2015, Volume 61, No. 24
Biomarkers of Sleep Debt Found in Humans and Rats
In a study published earlier this month in the Proceedings of the National Academy of Sciences, Amita Sehgal, a professor of neuroscience at the Perelman School of Medicine at the University of Pennsylvania and a Howard Hughes Medical Institute investigator, along with co-first authors Aalim M. Weljie, a research assistant professor of systems pharmacology and translational therapeutics and Peter Meerlo, from the University of Groningen, The Netherlands, found common molecules signifying perturbed metabolism in response to sleep restriction in a comprehensive metabolic profiling of blood from both rats and humans. Their findings point to an overall shift in how lipids are metabolized and evidence of systemic oxidative stress due to decreased sleep in both species.
Oxidative stress and lipid metabolism are important factors in metabolic diseases, although further work needs to be done to establish a mechanistic link between the markers found and specific diseases, stress the researchers.
“One possibility is that sleep drives metabolite clearance and so acts as a reparative process at the metabolic level,” said Dr. Sehgal. “The impact of sleep restriction on circadian biology is particularly relevant given what we now know about how metabolites also oscillate in humans on a daily basis.” Metabolites are chemical intermediates or end products of metabolism, so while they are generated through the breakdown of fats, carbohydrates and proteins, their function is not restricted to these processes.
The team subjected rats and humans to chronic sleep restriction over five days. Sleep restriction, versus sleep deprivation, curtails sleep time, but does not eliminate sleep. “Sleep restriction more closely represents real-world situations in humans and is a condition experienced by millions of people every day,” noted Dr. Sehgal.
In both studies, metabolite levels were compared in blood that was collected following adequate sleep opportunity in rats and humans to establish a baseline and then following restricted sleep. The team then produced a comprehensive metabolite profile from the blood of sleep-restricted rats and humans. Overall, they found a significant shift in lipid metabolism, with sleep restriction, with higher levels of phospholipids in both rats and humans. The team found that some neurotransmitters and gut metabolites (possibly from intestinal microbes) are also altered due to sleep restriction.
When they compared the list of significantly altered metabolites in rats and humans compared to the baseline before sleep restriction, they found that two metabolites—oxalic acid and diacylglycerol 36:3—were depleted under sleep-restricted conditions and restored after recovery sleep in both species. Oxalic acid is a waste product derived from processing foods in the diet such as plants, primarily from the breakdown of vitamin C and some amino acids. Diacylglycerol is a precursor molecule in the production of triglycerides, a molecule in which most fat is stored in the body, and also has a function in signaling in cells. The researchers suggest that these two molecules could serve as potential biomarkers since they are present in both species.
“These cross-species markers are exciting for a couple reasons,” added Dr. Weljie. “First, there is a need for quantitative markers of sleep debt and sleep quality, and this approach suggests that metabolites may be useful in this regard. Second, because we found the same metabolites in the humans and rats, it opens the door for us investigate mechanistic questions regarding the metabolic effects of sleep in rats that may have clinical and therapeutic application.”
Haters Spend More Time… Hating?
A new study published in the journal Social Psychology found that a person’s “dispositional attitude”–whether the person is a “hater” or a “liker”–plays an important role in his or her activity level.
The article, “Liking more means doing more: Dispositional attitudes predict patterns of general action,” is written by Justin Hepler, department of psychology, University of Illinois at Urbana-Champaign; and Dolores Albarracín, Annenberg School for Communication and department of psychology, University of Pennsylvania. Assuming that our disposition motivates behavior, Dr. Hepler and Dr. Albarracín suggested that people who like many things (those with positive dispositional attitudes) also do many things during the course of a week, while people who dislike many things (those with low dispositional attitudes) do very few things with their time.
They were right. In two studies, participants reported all of their activities over a one-week period and also completed a measure of dispositional attitudes. Although haters (someone with a low dispositional attitude) and likers (someone with a high dispositional attitude) did not differ in the types of activities they pursued, haters tended to do fewer activities throughout the week than did likers. Nearly 15 percent of the differences in how many activities people conducted during a typical week was associated with being a hater versus a liker. Haters and likers also did not differ in how much time they spent doing activities throughout the week; they merely differed in the number of activities that they did. As a result, haters spent more time on any given activity than did likers. Thus, compared with likers, haters could be characterized as less active because they do fewer things, or they could be characterized as more focused because they spend more time on the small number of things they do.
“The present results demonstrate that patterns of general action may occur for reasons other than the desire to be active versus inactive,” the researchers wrote. “Indeed, some people may be more active than others not because they want to be active per se, but because they identify a large number of specific behaviors in which they want to engage.” Dr. Hepler and Dr. Albarracín suggest that their findings may have implications for understanding the development of skills and expertise. For example, likers may adopt a jack-of-all-trades approach to life, investing small amounts of time in a wide variety of activities. This would leave them somewhat skilled at many tasks. In contrast, when haters find an activity they actually like, they may invest a larger amount of time in that task, allowing them to develop a higher skill level compared to likers. They said future work should confirm this possibility.
This same pattern could also be relevant to attentional control. For example, likers may have more difficulty sustaining attention on a task because they perceive so many interesting and distracting opportunities in their environment. In contrast, because haters like so few things, they may be unlikely to be distracted when they are doing a task, and thus their generalized dislike may actually benefit their attentional control.
Abuses Suffered Abroad by Nepal’s Migrant Workers
A two-year study, “Migrant Workers’ Access to Justice at Home: Nepal,” was published by the Open Society Foundations and co-authored by Sarah Paoletti, director of the Transitional Legal Clinic at the University of Pennsylvania Law School, with colleagues Eleanor Taylor-Nicholson of University of New South Wales, Bandita Sijapati of the Centre for the Study of Labour and Mobility and Bassina Farbenblum of the University of New South Wales.
According to the study, each month approximately 16,000 Nepalis travel to the Gulf States for temporary work, with thousands more traveling to other Middle East countries for employment, the majority of whom suffer high levels of abuse and exploitation, including misrepresentation of the nature and terms of work available, non-payment of wages and over-charging of recruitment fees, among other illegal practices. More- over, the study finds Nepal’s government, despite efforts to protect migrant workers, is failing to hold private recruiting agencies and individuals accountable for a variety of illegal acts.
According to Ms. Paoletti, “Vulnerability to exploitation abroad is often heightened by routine violations committed in Nepal during the pre-departure phase by individual agents, recruitment agencies and other private actors.” These illegal abuses endured by migrant workers, the report finds, in some cases lead to labor trafficking, forced labor and debt bondage abroad. Nepal has established laws and mechanisms to regulate labor migration and provide redress to workers who are exploited or otherwise harmed during the recruitment process, throughout the migration process, or once employed. The government strengthened its labor migration framework with the introduction of its Foreign Employment Act in 2007, the Foreign Employment Rules in 2008 and the Foreign Employment Policy of 2012. But, the authors write, “it has not taken sufficient steps to prevent common harms, or to ensure adequate redress and accountability when they occur.” The problem, according to the study, is that existing laws “set forth clear obligations on the part of recruitment agencies, agents, intending migrant workers and the entities established to oversee implementation.”
owever, the law routinely “fails to include explicit corresponding and enforceable rights for workers when those parties fail to meet their obligations.”
Because of this, the study concludes, “access to justice for large numbers of Nepali migrant workers remains elusive.” For example, of the 54 migrant workers the authors interviewed for the study—all of whom had suffered some harm as part of their employment arrangements—none had obtained full redress through Nepal’s legal or regulatory frameworks. The report details how Nepal’s Foreign Employment Act and Foreign Employment Rules set forth relatively robust regulations for the recruitment of workers for foreign employment, but “much more needs to be done to improve government oversight and transparency in the process, particularly during the pre-departure phase of labor migration.”
“Improving access to justice for migrant workers requires reforming the specific redress mechanisms available to migrant workers, and considering new mechanisms,” the authors contend. “It also requires broader changes to the labor migration system overall, including increased transparency and more effective oversight and regulation to hold all public and private actors within the system to greater account.”
Launch of PTSD Toolkit
PTSD Toolkits have been developed by the University of Pennsylvania School of Nursing, in response to President Obama’s call to deliver quality health care to veterans. The American Nurses Foundation (ANF), the philanthropic arm of the American Nurses Association (ANA), announced the launch of the interactive, web-based post-traumatic stress disorder (PTSD) Toolkit that was developed in partnership with Penn Nursing to help civilian registered nurses (RNs) better assess and treat PTSD in the nation’s veterans and military service members. The PTSD Toolkit was highlighted in a White House fact sheet as an innovative way to address veterans’ mental health.
PTSD is a cluster of symptoms that occur when a person experiences or witnesses a threat of injury or death. It is estimated that half a million veterans and military service members suffer the disabling agitation, nightmares and emotional withdrawal that characterize this disorder.
To improve nurse competency in screening and intervening with PTSD in military members, in June of 2013, ANF made an $85,000 grant, made possible by funding from the Jessie Ball DuPont Fund, to Penn Nursing to develop the toolkit. Penn Nursing’s Nancy Hanrahan led the team that worked on the project, which also included doctoral students, Matthew Lee, Grace Olamijulo and Pamela Herbig Wall; Lisa Seng, second degree nursing student; Warren Longmire, software developer; and Lucas Blair, co-founder of Little Bird Games.
“Nurses often represent the first point of contact for veterans and military personnel seeking care. We want them to have tools to help veterans find the help they need to transition back to civilian life,” Dr. Hanrahan said. “The PTSD Toolkit’s care interventions maximize the potential for self-care management and help move veterans to providers and programs that can help them. PTSD can be treated and cured. Failed transitions from military life to civilian life are unacceptable outcomes.” The interactive, PTSD-focused website and an e-learning module are based on advanced gaming techniques that will provide immediate access to materials for RNs to assess, treat and refer military members and veterans for help with their symptoms. These e-learning tools will certify that an RN is grounded in assessment, treatment, referral and non-stigmatizing educational approaches to self-care and mutual help.
Joining Forces is a national initiative led by First Lady Michelle Obama and Jill Biden to engage all sectors of society to give our service members and their families the opportunities and support they have earned. In 2012, ANA, in coordination with the Departments of Veterans Affairs (VA) and Defense, convened a coordinated effort of more than 160 state and national nursing organizations and more than 500 nursing schools to ensure the nation’s 3.1 million nurses can better meet the unique health needs of service members, veterans and their families. The First Lady and Dr. Biden announced this initiative at Penn Nursing in April 2012 (Almanac April 17, 2012).
ANF has prioritized support of the ANA Joining Forces initiative as a key component to its mission of “transforming the nation’s health through the power of nursing.” ANF will distribute the Toolkit nationally via nursing publications, websites, emails and newsletters of nursing associations and schools. The Toolkit is available at www.nurseptsdtoolkit.org
Brain Activity after Smokers Quit Predicts Relapsing
Reporting in a study published last month in the journal Neuropsychopharmacology, James Loughead, associate professor of psychiatry, and Caryn Lerman, a professor of psychiatry and director of Penn’s Center for Interdisciplinary Research on Nicotine Addiction, found that smokers who relapsed within seven days from their target quit date had specific disruptions in the brain’s working memory system during abstinence that separated them from the group who successfully quit. Such neural activity could help distinguish successful quitters from those who fail at an earlier stage and serve as a potentially therapeutic target for novel treatments.
“This is the first time abstinence-induced changes in the working memory have been shown to accurately predict relapse in smokers,” said senior author Dr. Lerman, who also serves as deputy director of Penn’s Abramson Cancer Center. The study’s lead author, Dr. Loughead, said, “The neural response to quitting even after one day can give us valuable information that could inform new and existing personalized intervention strategies for smokers, which is greatly needed.”
In the study, researchers used functional magnetic resonance imaging (fMRI) to explore the effects of brief abstinence from smoking on working memory and its associated neural activation in 80 smokers seeking treatment. Participants were between 18 and 65 and reported smoking more than 10 cigarettes a day for more than six months. Two fMRI sessions occurred: one immediately after a person smoked and one 24 hours after abstinence began. Following smoking cessation counseling, participants set a future target quit date. Seven days after the target quit date, participants completed a monitoring visit, during which smoking behavior was accessed, including a urine test. Sixty one smokers relapsed and 19 quit successfully for this period, the researchers reported.
Those who relapsed had decreased activity in the left dorsolateral prefrontal cortex, which controls executive functions, like working memory, compared to those who quit. Working memory is an essential cognitive function necessary for staying focused, blocking distractions and completing tasks. They also had reduced suppression of activation in the posterior cingulate cortex, a central part of the default mode network of the brain, which is more active when people are in a so-called “introspective” or “self-referential” state.
A past study in JAMA Psychiatry from Dr. Lerman and colleagues published earlier this year showed how smokers suffering from nicotine withdrawal have more trouble shifting from the default mode network into the executive control network, where people can exert more conscious, self-control over cravings and to focus on quitting for good. However, this new study is the first to use that brain activity to help predict relapse in smokers.
Researchers determined predictive values of a relapse model that includes the working memory data. Using resampling methods that generate 1,000 replicates of the data from the 80 smokers, they found that incorporating the working memory-related brain activity resulted in an 81 percent correct prediction rate, a significant improvement over the 73 percent for the model of withdrawal symptoms and demographic/smoking history predictors and the 67 percent for demographic/smoking history predictors only.
Fear of Crime Related to Prime-Time Television Violence
Has watching television made people afraid of crime? A new study finds that Americans’ answer to one of the long-running questions in a Gallup poll—are you afraid to walk alone in your neighborhood at night?—may be influenced by the amount of violence shown on television dramas. The study by researchers at the Annenberg Public Policy Center (APPC) of the University of Pennsylvania found that the American public’s fear of crime is statistically related to the amount of violence portrayed on prime-time TV.
Published in the online journal Media and Communication, the study compared annual changes in the amount of violence portrayed on popular prime-time broadcast dramas from 1972 through 2010 with changes in national rates of response to the Gallup poll question over that period.
Even though the actual crime rate has fallen, according to FBI statistics, the study found that TV violence has increased since the late 1990s. The public’s fear of crime, as assessed by the Gallup annual crime survey, has also begun to rise again since that time.
“We now have stronger evidence that the fictional treatment of crime on TV may influence the public’s fears of crime,” said Dan Romer, co-author of the study and an associate director of the APPC.
APPC researchers studied violent sequences in 475 hours of commercial-free nighttime broadcast dramas, which included a heavy representation of police, legal and medical shows. The researchers found—even after factoring out changes in FBI crime rates and people’s perceptions of change in crime rates—that the poll results fell and rose along with TV violence.
The number of violent sequences per TV hour fell from a high of 6.5 in 1972 to 1.4 in 1996, and then increased to 3.7 in 2010. Each additional violent sequence per hour predicted an increase of 1 percentage point in the people who told Gallup they were afraid of walking alone at night in their neighborhood.
“The findings are consistent with media scholarship in the 1960s and ’70s that predicted effects of fictional TV violence on audiences,” said Patrick E. Jamieson, the lead author of the study and director of APPC’s Adolescent Risk Communication Institute. “That prediction has been controversial, but with the present results, we have the best evidence to date that TV shows can affect how safe the public feels.”