University of Pennsylvania’s Mesothelioma Program Receives $8 Million Grant from NCI

The National Cancer Institute awarded an $8 million grant to the University of Pennsylvania’s Perelman School of Medicine to study the effects of photodynamic light therapy (PDT) in patients with malignant pleural mesothelioma. The grant will fund a clinical trial and additional studies looking at the effects of PDT on the patient’s immune response, the mesothelioma tumor cell , and the blood vessels surrounding the tumor.Dr. Eli Glatstein is the principal investigator of the program. He is also the professor and vice chair of Radiation Oncology, and member of Penn’s Mesothelioma and Pleural Program. According to Dr. Glatstein, “This trial represents a major step in understanding the combination of treatment modalities that will offer patients the best hope for survival and extended remission.”The study expects to …

Read more

Neurotics don’t just avoid action: They dislike it, study finds

That person we all seem to know who we say is neurotic and unable to take action? Turns out he or she isn’t unable to act but simply doesn’t want to.A study of nearly 4,000 college students in 19 countries has uncovered new details about why neurotic people may avoid making decisions and moving forward with life. Turns out that when they are asked if action is positive, favorable, good, they just don’t like it as much as non-neurotics. Therefore persuasive communications and other interventions may be useful if they simply alter neurotics’ attitudes toward inaction.These findings come the study “Neuroticism and Attitudes Toward Action in 19 Countries.” It is published in the Journal of Personality and was written by Molly E. Ireland, Texas Tech University; Justin Hepler, University of Illinois at Urbana-Champaign; Hong Li, Battelle Center for Analytics and Public Health; and Dolores Albarracn -the principal investigator of the study– from the Annenberg School for Communication, University of Pennsylvania.”You’re so neurotic!” It’s a phrase that’s tossed about casually, but what exactly is neuroticism? It is a personality trait defined by the experience of chronic negative affect — including sadness, anxiety, irritability, and self-consciousness — that is easily triggered and difficult to control. Neurotic people tend to avoid acting when confronted with major and minor life stressors, leading to negative life consequences.The researchers sought to determine whether and under what conditions neuroticism is associated with favorable or unfavorable representations of action and inaction. They investigated whether depression and anxiety would decrease proactive behavior among neurotic individuals, and whether a person’s collectivistic tendencies — considering the social consequences of one’s behavior before acting — would moderate the negative associations between neuroticism and action/inaction. The study found neurotics look at action less favorably and inaction more favorably than emotionally stable people do.”People who are less emotionally stable have less positive attitudes towards action and more positive attitudes toward inaction,” the authors wrote. “Furthermore, anxiety was primarily responsible for neurotic individuals’ less positive attitudes toward action. …

Read more

Mortality risks of being overweight or obese are underestimated

New research by Andrew Stokes, a doctoral student in demography and sociology in the School of Arts and Sciences at the University of Pennsylvania, suggests that many obesity studies substantially underestimate the mortality risks associated with excess weight in the United States. His study, “Using Maximum Weight to Redefine Body Mass Index Categories in Studies of The Mortality Risks of Obesity,” was published in the March issue of the open-access journal Population Health Metrics.”The scholarly community is divided over a large meta-analysis that found that overweight is the optimal BMI category and that there are no increased risks associated with obese class 1,” Stokes said.Normal weight is indicated by a BMI of 18.5-24.9 kg/m2, overweight is indicated by a BMI of 25.0-29.9 kg/m2, obese class 1 is a BMI of 30.0-34.9 kg/m2 and obese class 2 is a BMI of 35.0 kg/m2 and above.Skeptics of the meta-analysis argue that the findings are likely driven by biases, especially by illness-induced weight loss.”Using BMI at the time of the survey to assess the mortality risks of overweight and obesity is problematic, especially in older populations, because slimness can be a marker of illness,” Stokes said.Researchers have attempted to address this bias by eliminating ill people from their samples; however, according to Stokes, such measures are inadequate because information on illness is ascertained by self-reporting and not everyone with an illness has been diagnosed.Stokes used individuals’ highest BMI in life to predict mortality rates. He said that in the previous literature, the normal weight category combines data from low-risk, stable-weight individuals with high-risk individuals who have experienced weight loss. Use of weight histories makes it possible to separate the two groups and redefine the reference category as people who were a consistently normal weight throughout their lives.Stokes conducted the analyses using data from the National Health and Nutrition Examination Surveys of 1988-1994 and 1999-2004 linked to the National Death Index through 2006 on U.S. adults ages 50-84 who never smoked.He found that the percentage of mortality attributable to overweight and obesity in this group was 33 percent when assessed using maximum BMI. The comparable figure obtained using BMI at the time of survey was substantially smaller at 5 percent.”The source of the discrepancy became clear when I started looking more closely at peoples’ weight histories,” Stokes said.Stokes said that a considerable fraction of individuals classified as normal weight using BMI at time of survey were formerly overweight or obese. This group had substantially elevated mortality rates compared to individuals that were consistently normal weight throughout their lives, suggesting that for many of them the weight loss was related to an illness.He concluded that the findings provide simple and compelling evidence that the prior literature underestimates the impact of obesity on levels of mortality in the U.S. But Stokes said that his results need corroboration in future studies because maximum BMI was calculated from peoples’ recollection of their maximum weight, which may be subject to recall error. He said that his analysis should be replicated using longitudinal data with contemporaneous measures of height and weight across the lifecycle.Story Source:The above story is based on materials provided by University of Pennsylvania. Note: Materials may be edited for content and length.

Read more

Nicotine withdrawal weakens brain connections tied to self-control over cigarette cravings

People who try to quit smoking often say that kicking the habit makes the voice inside telling them to light up even louder, but why people succumb to those cravings so often has never been fully understood. Now, a new brain imaging study in this week’s JAMA Psychiatry from scientists in Penn Medicine and the National Institute on Drug Abuse (NIDA) Intramural Research Program shows how smokers suffering from nicotine withdrawal may have more trouble shifting from a key brain network — known as default mode, when people are in a so-called “introspective” or “self-referential” state — and into a control network, the so-called executive control network, that could help exert more conscious, self-control over cravings and to focus on quitting for good.The findings help validate a neurobiological basis behind why so many people trying to quit end up relapsing — up to 80 percent, depending on the type of treatment — and may lead to new ways to identify smokers at high risk for relapse who need more intensive smoking cessation therapy.The brain imaging study was led by researchers at University of Pennsylvania’s new Brain and Behavior Change Program, led by Caryn Lerman, PhD, who is also the deputy director of Penn’s Abramson Cancer Center, and Elliot Stein, PhD, and collaborators at NIDA. They found that smokers who abstained from cigarettes showed weakened interconnectivity between certain large-scale networks in their brains: the default mode network, the executive control network, and the salience network. They posit that this weakened connectivity reduces smokers’ ability to shift into or maintain greater influence from the executive control network, which may ultimately help maintain their quitting attempt.”What we believe this means is that smokers who just quit have a more difficult time shifting gears from inward thoughts about how they feel to an outward focus on the tasks at hand,” said Lerman, who also serves as the Mary W. Calkins professor in the Department of Psychiatry. “It’s very important for people who are trying to quit to be able to maintain activity within the control network — to be able to shift from thinking about yourself and your inner state to focus on your more immediate goals and plan.”Prior studies have looked at the effects of nicotine on brain interconnectivity in the resting state, that is, in the absence of any specific goal directed activity. This is the first study, however, to compare resting brain connectivity in an abstinent state and when people are smoking as usual, and then relate those changes to symptoms of craving and mental performance.For the study, researchers conducted brain scans on 37 healthy smokers (those who smoke more than 10 cigarettes a day) ages 19 to 61 using functional magnetic resonance imaging (fMRI) in two different sessions: 24 hours after biochemically confirmed abstinence and after smoking as usual.Imaging showed a significantly weaker connectivity between the salience network and default mode network during abstinence, compared with their sated state. Also, weakened connectivity during abstinence was linked with increases in smoking urges, negative mood, and withdrawal symptoms, suggesting that this weaker internetwork connectivity may make it more difficult for people to quit.Establishing the strength of the connectivity between these large-scale brain networks will be important in predicting people’s ability to quit and stay quit, the authors write. Also, such connectivity could serve as a clinical biomarker to identify smokers who are most likely to respond to a particular treatment.”Symptoms of withdrawal are related to changes in smokers’ brains, as they adjust to being off of nicotine, and this study validates those experiences as having a biological basis,” said Lerman. “The next step will be to identify in advance those smokers who will have more difficultly quitting and target more intensive treatments, based on brain activity and network connectivity.”Story Source:The above story is based on materials provided by Perelman School of Medicine at the University of Pennsylvania. …

Read more

Characterization of stink bug saliva proteins opens door to controlling pests

Brown marmorated stink bugs cause millions of dollars in crop losses across the United States because of the damage their saliva does to plant tissues. Researchers at Penn State have developed methods to extract the insect saliva and identify the major protein components, which could lead to new pest control approaches.”Until now, essentially nothing was known about the composition of stink bug saliva, which is surprising given the importance of these insects as pests and the fact that their saliva is the primary cause of feeding injury to plants and crop losses,” said Gary Felton, professor and head of the Department of Entomology. “Other than using synthetic pesticides, there have been few alternative approaches to controlling these pests. By identifying the major protein components of saliva, it now may be possible to target the specific factors in saliva that are essential for their feeding and, therefore, design new approaches for controlling stink bugs.”The team reported its results in PLOS ONE.According to Felton, stink bugs produce two types of saliva that are required for successful feeding. Watery saliva helps stink bugs to digest their food. Sheath saliva surrounds stink bugs’ mouthparts and hardens to prevent spillage of sap during feeding. The hardened “sheath” remains attached to the plant when the insect is finished feeding.”Unlike a chewing insect, which causes damage by removing plant tissue, stink bugs pierce plant tissue and suck nutrients from the plant,” said Michelle Peiffer, research support assistant. “During this process, stink bugs also deposit saliva onto the plant. The interaction between this saliva and the plant is what causes the cosmetic and physiological changes that make crops unmarketable.”To extract the two types of saliva from brown marmorated stink bugs, Felton and Peiffer first collected adult bugs from homes and fields in central Pennsylvania and maintained them in their laboratory.The researchers chilled the insects on ice. As the insects returned to room temperature, their watery saliva was secreted from the tips of their beaks. …

Read more

Cancer patients turning to mass media, non-experts for info

The increasing use of expensive medical imaging procedures in the U.S. like positron emission tomography (PET) scans is being driven, in part, by patient decisions made after obtaining information from lay media and non-experts, and not from health care providers.That is the result from a three-year-long analysis of survey data, and is published in the article , “Associations between Cancer-Related Information Seeking and Receiving PET Imaging for Routine Cancer Surveillance — An Analysis of Longitudinal Survey Data,” appearing in the journal Cancer Epidemiology, Biomarkers & Prevention. Andy S. Tan, Ph.D., a post-doctoral fellow with the University of Pennsylvania’s Annenberg School for Communication, is the lead author of the study. Co-authors are Laura Gibson, Ph.D.; Hanna M. Zafar, MD; Stacy W. Gray, MD; Robert C. Hornik, Ph.D.; and Katrina Armstrong, MD.Data for this analysis were obtained from a longitudinal cohort study comprising three annual mailed surveys between 2006 and 2008 and completed by patients diagnosed with breast, prostate, or colorectal cancers. Over 2,000 individuals participated in the study, funded by the National Cancer Institute.”Clinical guidelines do not recommend PET for post-treatment surveillance among asymptomatic cancer survivors,” explains Dr. Tan and the study’s other authors. …

Read more

The parasite that escaped out of Africa: Tracing origins of malaria parasite

An international team of scientists has traced the origin of Plasmodium vivax, the second-worst malaria parasite of humans, to Africa, according to a study published this week in Nature Communications. Until recently, the closest genetic relatives of human P. vivax were found only in Asian macaques, leading researchers to believe that P. vivax originated in Asia.The study, led by researchers from the Perelman School of Medicine at the University of Pennsylvania, found that wild-living apes in central Africa are widely infected with parasites that, genetically, are nearly identical to human P. vivax.This finding overturns the dogma that P. vivax originated in Asia, despite being most prevalent in humans there now, and also solves other vexing questions about P. vivax infection: how a mutation conferring resistance to P. vivax occurs at high frequency in the very region where this parasite seems absent and how travelers returning from regions where almost all humans lack the receptor for P. vivax can be infected with this parasite.Of Ape and Human ParasitesMembers of the labs of Beatrice Hahn, MD, and George Shaw, MD, PhD, both professors of Medicine and Microbiology at Penn, in collaboration with Paul Sharp, PhD, an evolutionary biologist from the University of Edinburgh, and Martine Peeters, PhD, a microbiologist from the Institut de Recherche pour le Dveloppement and the University of Montpellier, tested over 5,000 ape fecal samples from dozens of field stations and sanctuaries in Africa for P. vivax DNA. …

Read more

Cell therapy shows remarkable ability to eradicate cancer in clinical study

Investigators from Memorial Sloan Kettering Cancer Center have reported more encouraging news about one of the most exciting methods of cancer treatment today. The largest clinical study ever conducted to date of patients with advanced leukemia found that 88 percent achieved complete remissions after being treated with genetically modified versions of their own immune cells. The results were published today in Science Translational Medicine.”These extraordinary results demonstrate that cell therapy is a powerful treatment for patients who have exhausted all conventional therapies,” said Michel Sadelain, MD, PhD, Director of the Center for Cell Engineering at Memorial Sloan Kettering and one of the study’s senior authors. “Our initial findings have held up in a larger cohort of patients, and we are already looking at new clinical studies to advance this novel therapeutic approach in fighting cancer.”Adult B cell acute lymphoblastic leukemia (B-ALL), a type of blood cancer that develops in B cells, is difficult to treat because the majority of patients relapse. Patients with relapsed B-ALL have few treatment options; only 30 percent respond to salvage chemotherapy. Without a successful bone marrow transplant, few have any hope of long-term survival.In the current study, 16 patients with relapsed B-ALL were given an infusion of their own genetically modified immune cells, called T cells. The cells were “reeducated” to recognize and destroy cancer cells that contain the protein CD19. While the overall complete response rate for all patients was 88 percent, even those with detectable disease prior to treatment had a complete response rate of 78 percent, far exceeding the complete response rate of salvage chemotherapy alone.Dennis J. Billy, C.Ss.R, of Wynnewood, Pennsylvania, was one of the first patients to receive this treatment more than two years ago. He was able to successfully undergo a bone marrow transplant and has been cancer-free and back at work teaching theology since 2011. …

Read more

Physician urges greater recognition of how ‘misfearing’ influences women’s perceptions of heart health risks

While more women die from heart disease each year than all forms of cancer combined, many are more fearful of other diseases, particularly breast cancer. This phenomenon, referred to as “misfearing,” describes the human tendency to fear instinctively and according to societal influences rather than based on facts. This trend may be a contributor to the reasons why many women fail to take enough steps — such as changing diet and fitness habits or risk-taking behaviors — to guard against heart disease.In a Perspective column today in the New England Journal of Medicine, Penn Medicine cardiologist and Robert Wood Johnson Foundation Clinical Scholar Lisa Rosenbaum, MD, notes that although the first decade of educational campaigns to inform women about heart disease “led to a near doubling of women’s knowledge about heart disease, in the past few years, such efforts have failed to reap further gains.” Moreover, “persistent gaps in perceptions remain among minority women, who are often at greatest risk.”Simply reinforcing the facts about the prevalence and potential prevention of heart disease among women is likely not enough to improve on these results, says Rosenbaum. Instead, physicians and others in health care need to develop an understanding of the misfearing paradigm and how “social values” and “group identities” affect patients’ perceptions of disease.”The big, the dramatic, and the memorable occupy far more of our worry budget than the things that kill with far greater frequency: strokes, diabetes, heart disease,” she writes. “But interacting with many of these fear factors is another force we rarely associate with our individual health perceptions: our commitment to our cultural groups.”Women’s focus on breast cancer may be tied, according to Rosenbaum, to “intuitions about female identity” that shape their interpretation of health-related information and relevant behavior. Because breast cancer “attacks a body part that is so fundamental to female identity,” she asks if “to be a woman, one must join the war on this disease,” and consequently focus less on heart disease (which is often linked to such perceived anti-feminine contributing factors as cigarettes and obesity). Additionally, Rosenbaum asks, “Are we held up by our ideal of beauty? We can each summon the images of beautiful young women with breast cancer. Where are all the beautiful women with heart disease?”While acknowledging the very real threat of women’s cancers, Dr. Rosenbaum advocates physicians taking a different approach to conversations with female patients about cardiovascular health. …

Read more

New fruitfly sleep gene promotes the need to sleep

All creatures great and small, including fruitflies, need sleep. Researchers have surmised that sleep — in any species — is necessary for repairing proteins, consolidating memories, and removing wastes from cells. But, really, sleep is still a great mystery.The timing of when we sleep versus are awake is controlled by cells in tune with circadian rhythms of light and dark. Most of the molecular components of that internal clock have been worked out. On the other hand, how much we sleep is regulated by another process called sleep homeostasis, however little is known about its molecular basis.In a study published in eLIFE, Amita Sehgal, PhD, professor of Neuroscience at the Perelman School of Medicine, University of Pennsylvania, and colleagues, report a new protein involved in the homeostatic regulation of sleep in the fruitfly, Drosophila. Sehgal is also an investigator with the Howard Hughes Medical Institute (HHMI).The researchers conducted a screen of mutant flies to identify short-sleeping individuals and found one, which they dubbed redeye. These mutants show a severe reduction in the amount of time they slumber, sleeping only half as long as normal flies. While the redeye mutants were able to fall asleep, they would wake again in only a few minutes.The team found that the redeye gene encodes a subunit of the nicotinic acetylcholine receptor. This type of acetylcholine receptor consists of multiple protein subunits, which form an ion channel in the cell membrane, and, as the name implies, also binds to nicotine. Although acetylcholine signaling — and cigarette smoking — typically promote wakefulness, the particular subunit studied in the eLIFE paper is required for sleep in Drosophila.Levels of the redeye protein in the fly oscillate with the cycles of light and dark and peak at times of daily sleep. …

Read more

Mesothelioma Blood Test-Mesomark Test

The reason for high death rates among mesothelioma patients is the aggressive nature of the disease and the inability to diagnose it until it is well advanced. Because mesothelioma symptoms do not show up until about 40-50 years after exposure to asbestos, most cases at the time of diagnosis have already reached Stage III or IV. As a result, mesothelioma treatment options are often more palliative than curative.However, the ability to diagnose the disease at an earlier time would certainly result in a better prognosis for mesothelioma patients. That ability is now present in the form of a mesothelioma blood test known as Mesomark. Developed by Fujirebio Diagnostics Inc. of Malvern, Pennsylvania, a leader in the field of oncology testing, the test measures the amount of a …

Read more

Children benefit from positive peer influence in afterschool programs

Sep. 4, 2013 — Children in afterschool programs who have a sense of connectedness with their peers are less likely to report emotional problems, according to Penn State researchers. Children exhibited fewer behavior problems if they perceived their peers were willing to encourage them to behave well.”Encouraging your friends to do something positive or to not misbehave may start from selfishness because you want your group to earn a certain activity or privilege, but it turns into working together as a team,” said Emilie Phillips Smith, professor of human development and family studies.She and colleagues observed the relationships children in after school programs had with each other and with staff. The researchers also conducted surveys to determine the frequency of problem behavior in the children. Problem behavior included smoking cigarettes, damaging property, drinking alcohol, shoplifting and smoking marijuana.Thirteen percent of the children in this study reported purposely breaking and damaging property that belongs to someone else. This was the most frequently reported problem behavior.Girls were more likely to feel connected to their peers and to intervene if something was wrong. They also reported fewer incidents of problem behavior.The younger elementary-age children in the study were more likely to act out than the older children, and were less likely to report feeling connected to their peers.”Yet, it is exciting to note the differences we didn’t see — particularly that we found no racial or ethnic differences,” said Smith.Researchers refer to the social cohesion of a particular group combined with willingness to intervene for the common good of the group as collective efficacy, and among adults it has been linked to reduced violence as well as less deviant and delinquent behavior in neighborhoods. Smith noted that much more attention has been given to these concepts among adults, and that collective efficacy in youth has rarely been studied.”Too often, we don’t create a place where youth can grow, develop and have a hand in shaping their own environments,” said Smith.The researchers measured collective efficacy by focusing on children participating in after school programs in three different areas of south central Pennsylvania. Children in grades two through five answered survey questions about how connected they felt to the other children in the program, their willingness to get involved if another child was misbehaving and the types of problem behaviors they had participated in and how often.Strong collective efficacy in children had a similar effect on the group as it did for adults in previous studies, the researchers found. In particular, the same two dimensions were significant in fostering collective efficacy, the researchers reported in a recent issue of the American Journal of Community Psychology.”We worked with three very different school districtsand we didn’t find significant differences in these relationships across these three locales, though they differed substantially in racial-ethnic composition and socio-economic status,” said Smith. …

Read more

Biologists show that generosity leads to evolutionary success

Sep. 2, 2013 — With new insights into the classical game theory match-up known as the “Prisoner’s Dilemma,” University of Pennsylvania biologists offer a mathematically based explanation for why cooperation and generosity have evolved in nature.Their work builds upon the seminal findings of economist John Nash, who advanced the field of game theory in the 1950s, as well as those of computational biologist William Press and physicist-mathematician Freeman Dyson, who last year identified a new class of strategies for succeeding in the Prisoner’s Dilemma.Postdoctoral researcher Alexander J. Stewart and associate professor Joshua B. Plotkin, both of Penn’s Department of Biology in the School of Arts and Sciences, examined the outcome of the Prisoner’s Dilemma as played repeatedly by a large, evolving population of players. While other researchers have previously suggested that cooperative strategies can be successful in such a scenario, Stewart and Plotkin offer mathematical proof that the only strategies that succeed in the long term are generous ones. They report their findings in PNAS the week of Sept. 2.”Ever since Darwin,” Plotkin said, “biologists have been puzzled about why there is so much apparent cooperation, and even flat-out generosity and altruism, in nature. The literature on game theory has worked to explain why generosity arises. Our paper provides such an explanation for why we see so much generosity in front of us.”The Prisoner’s Dilemma is a way of studying how individuals choose whether or not to cooperate. In the game, if both players cooperate, they both receive a payoff. …

Read more

Prehistoric climate shift linked to cosmic impact

Sep. 2, 2013 — For the first time, a dramatic climate shift that has long fascinated scientists has been linked to the impact in Quebec of an asteroid or comet, Dartmouth researchers and their colleagues report in a new study funded by the National Science Foundation.The event took place about 12,900 years ago, at the beginning of the Younger Dryas period, and marks an abrupt global change to a colder, dryer climate, with far-reaching effects on both animals and humans, the scientists say. In North America the big animals, including mastodons, camels, giant ground sloths, and saber-toothed cats, all vanished. Their human hunters, known to archaeologists as the Clovis people, set aside their heavy-duty spears and turned to a hunter-gatherer subsistence diet of roots, berries, and smaller game.”The Younger Dryas cooling is a very intriguing event that impacted human history in a profound manner,” says Mukul Sharma, a professor in the Department of Earth Sciences and one of the authors of a new paper published in the Proceedings of the National Academy of Sciences (PNAS). “Environmental stresses may also have caused Natufians in the Near East to settle down for the first time and pursue agriculture.”That these powerful environmental changes occurred is not in dispute, but there has been controversy over why they happened. The new PNAS paper focuses on one cause: a comet or meteor striking Earth.The classical view of the Younger Dryas cooling interlude has been that a surge of meltwater from the North American ice sheet was behind it all. According to this theory, a large quantity of fresh water accumulated behind an ice dam. The dam suddenly ruptured and dumped all this water into the Atlantic Ocean. The sudden influx is thought to have shut down the ocean currents that move tropical water northward, resulting in the cold, dry climate of the Younger Dryas.However, Sharma and his colleagues from Dartmouth and other institutions have discovered conclusive evidence linking an extraterrestrial impact with this environmental transformation. The PNAS paper presents a scenario in which a meteor or a comet collided with Earth.The report focuses on spherules, droplets of solidified molten rock expelled by the impact. …

Read more

Great Recession onset spurs harsh parenting

Aug. 5, 2013 — The onset of the Great Recession and, more generally, deteriorating economic conditions lead mothers to engage in harsh parenting, such as hitting or shouting at children, a team of researchers has found. But the effect is only found in mothers who carry a gene variation that makes them more likely to react to their environment.The study, conducted by scholars at New York University, Columbia University, Princeton University, and Pennsylvania State University’s College of Medicine, appears in the journal Proceedings of the National Academy of Sciences (PNAS).”It’s commonly thought that economic hardship within families leads to stress, which, in turn, leads to deterioration of parenting quality,” said Dohoon Lee, an assistant professor of sociology at NYU and lead author of the paper. “But these findings show that an economic downturn in the larger community can adversely affect parenting — regardless of the conditions individual families face.”The researchers found that harsh parenting increased as economic conditions worsened only for those with what has been called the “sensitive” allele, or variation, of the DRD2 Taq1A genotype, which controls the synthesis of dopamine, a behavior-regulating chemical in the brain. Deteriorating economic conditions had no effect on the level of harsh parenting of mothers without the sensitive allele. Just more than half of the mothers in the study had the sensitive, or T, allele.Likewise, the researchers found that mothers with the sensitive allele had lower levels of harsh parenting when economic conditions were improving compared with those without the sensitive allele.”This finding provides further evidence in favor of the orchid-dandelion hypothesis that humans with sensitive genes, like orchids, wilt or die in poor environments, but flourish in rich environments, whereas dandelions survive in poor and rich environments,” said Irwin Garfinkel, a co-author of the paper and the Mitchell I. Ginsberg Professor of Contemporary Urban Problems at the Columbia University School of Social Work.The findings were based on data from the Fragile Families and Child Wellbeing Study (FFS), a population-based, birth cohort study conducted by researchers at Princeton and Columbia of nearly 5,000 children born in 20 large American cities between 1998 and 2000. Mothers were interviewed shortly after giving birth and when the child was approximately 1, 3, 5, and 9 years old. Data on harsh parenting were collected when the child was 3, 5, and 9 years old. In Year 9, saliva DNA samples were collected from 2,600 mothers and children.Harsh parenting was measured using 10 items from the commonly used Conflict Tactics Scale — five items measured psychological harsh parenting (e.g., shouting, threatening, etc.) and five gauged corporal punishment (e.g., spanking, slapping).The researchers supplemented these data with measurements of economic conditions in each of the 20 cities where the FFS mothers lived. …

Read more

Locating the brain’s GPS: Human neurons link to navigation in open environments

Aug. 4, 2013 — Using direct human brain recordings, a research team from Drexel University, the University of Pennsylvania, UCLA and Thomas Jefferson University has identified a new type of cell in the brain that helps people to keep track of their relative location while navigating an unfamiliar environment.The “grid cell,” which derives its name from the triangular grid pattern in which the cell activates during navigation, is distinct among brain cells because its activation represents multiple spatial locations. This behavior is how grid cells allow the brain to keep track of navigational cues such as how far you are from a starting point or your last turn. This type of navigation is called path integration.”It is critical that this grid pattern is so consistent because it shows how people can keep track of their location even in new environments with inconsistent layouts,” said Dr. Joshua Jacobs, an assistant professor in Drexel’s School of Biomedical Engineering, Science and Health Systems, who is the team’s primary investigator.The researchers, Jacobs, Dr. Michael Kahana, from Penn, and UCLA’s Dr. Itzhak Fried were able to discern these cells because they had the rare opportunity to study brain recordings of epilepsy patients with electrodes implanted deep inside their brains as part of their treatment. Their work is being published in the latest edition of Nature Neuroscience.During brain recording, the 14 study participants played a video game that challenged them to navigate from one point to another to retrieve objects and then recall how to get back to the places where each object was located. The participants used a joystick to ride a virtual bicycle across a wide-open terrain displayed on a laptop by their hospital beds. After participants made trial runs where each of the objects was visible in the distance, they were put back at the center of the map and the objects were made invisible until the bicycle was right in front of them. …

Read more

New variants at gene linked to kidney disease, sleeping sickness resistance

July 31, 2013 — A new study led by University of Pennsylvania researchers involves a classic case of evolution’s fickle nature: a genetic mutation that protects against a potentially fatal infectious disease also appears to increase the risk of developing a chronic, debilitating condition.Such a relationship exists between malaria and sickle cell anemia. Individuals who carry a gene to resist the former are carriers for the latter. And recently scientific evidence has suggested that individuals who are resistant to human African trypanosomiasis, or sleeping sickness, are predisposed to developing chronic kidney disease. That could explain why African-Americans, who derive much of their ancestry from regions where sleeping sickness is endemic, suffer from kidney disease at high rates.In a study published in the American Journal of Human Genetics, Penn researchers and colleagues offer further insights into the unfinished story of the sleeping sickness-kidney disease connection by looking at a variety of African populations which had not been included in prior studies. Sequencing a portion of a gene believed to play a role in both diseases, the scientists discovered new candidate variants that are targeted by recent natural selection. Their findings lend support to the idea that the advantages of resistance to sleeping sickness, a disease which continues to affect tens of thousands of sub-Saharan Africans each year, may have played a role in the evolution of populations across Africa.The research was led by Wen-Ya Ko and Sarah Tishkoff of the Department of Genetics in Penn’s Perelman School of Medicine. Tishkoff, a Penn Integrates Knowledge professor, also has an appointment in the School of Arts and Sciences’ Department of Biology. Ko now holds a research position at the Universidade do Porto in Portugal.Earlier research had shown that African-Americans with kidney disease frequently had one of two mutations in the gene that codes for the ApoL1 protein, endowing it with the ability to kill the parasite species that causes the form of sleeping sickness found in eastern Africa. But, puzzlingly, these variants were found at high frequencies in the Yoruba, who live in western Africa’s Nigeria.”That was an interesting finding, but nobody had ever done a sequencing analysis of this gene across other African populations,” Tishkoff said. “We wanted to know if we would find the same variants and would they be as common.”Using the earlier findings as a starting point, the Penn-led study expanded the sequencing effort to look at a region of the ApoL1 gene in 10 different African populations, encompassing groups from both eastern and western Africa.They found the G1 and G2 haplotypes in some of the other populations but only at low frequencies, suggesting there may be other variants playing a similar role. …

Read more

Evolution on the inside track: How viruses in gut bacteria change over time

July 26, 2013 — Humans are far more than merely the sum total of all the cells that form the organs and tissues. The digestive tract is also home to a vast colony of bacteria of all varieties, as well as the myriad viruses that prey upon them. Because the types of bacteria carried inside the body vary from person to person, so does this viral population, known as the virome.By closely following and analyzing the virome of one individual over two-and-a-half years, researchers from the Perelman School of Medicine at the University of Pennsylvania, led by professor of Microbiology Frederic D. Bushman, Ph.D., have uncovered some important new insights on how a viral population can change and evolve — and why the virome of one person can vary so greatly from that of another. The evolution and variety of the virome can affect susceptibility and resistance to disease among individuals, along with variable effectiveness of drugs.Their work was published in the Proceedings of the National Academy of Sciences.Most of the virome consists of bacteriophages, viruses that infect bacteria rather than directly attacking their human hosts. However, the changes that bacteriophages wreak upon bacteria can also ultimately affect humans.”Bacterial viruses are predators on bacteria, so they mold their populations,” says Bushman. “Bacterial viruses also transport genes for toxins, virulence factors that modify the phenotype of their bacterial host.” In this way, an innocent, benign bacterium living inside the body can be transformed by an invading virus into a dangerous threat.At 16 time points over 884 days, Bushman and his team collected stool samples from a healthy male subject and extracted viral particles using several methods. They then isolated and analyzed DNA contigs (contiguous sequences) using ultra-deep genome sequencing .”We assembled raw sequence data to yield complete and partial genomes and analyzed how they changed over two and a half years,” Bushman explains. The result was the longest, most extensive picture of the workings of the human virome yet obtained.The researchers found that while approximately 80 percent of the viral types identified remained mostly unchanged over the course of the study, certain viral species changed so substantially over time that, as Bushman notes, “You could say we observed speciation events.”This was particularly true in the Microviridae group, which are bacteriophages with single-stranded circular DNA genomes. Several genetic mechanisms drove the changes, including substitution of base chemicals; diversity-generating retroelements, in which reverse transcriptase enzymes introduce mutations into the genome; and CRISPRs (Clustered Regularly Interspaced Short Palindromic Repeats), in which pieces of the DNA sequences of bacteriophages are incorporated as spacers in the genomes of bacteria.Such rapid evolution of the virome was perhaps the most surprising finding for the research team. …

Read more

Major cities often safest places in the US

July 23, 2013 — Overturning a commonly-held belief that cities are inherently more dangerous than suburban and rural communities, researchers from the Perelman School of Medicine at the University of Pennsylvania and the Children’s Hospital of Philadelphia (CHOP) have found that risk of death from injuries is lowest on average in urban counties compared to suburban and rural counties across the U.S.The new study, which appears online ahead of print in the Annals of Emergency Medicine, found that for the entire population, as well as for most age subgroups, the top three causes of death were motor vehicle collisions, firearms, and poisoning. When all types of fatal injuries are considered together, risk of injury-related death was approximately 20 percent lower in urban areas than in the most rural areas of the country.”Perceptions have long existed that cities were innately more dangerous than areas outside of cities, but our study shows this is not the case” said lead study author, Sage R. Myers, MD, MSCE, assistant professor of Pediatrics, Perelman School of Medicine and attending physician, Department of Emergency Medicine at CHOP. “These findings may lead people who are considering leaving cities for non-urban areas due to safety concerns to re-examine their motivations for moving. And we hope the findings could also lead us to re-evaluate our rural health care system and more appropriately equip it to both prevent and treat the health threats that actually exist.”The study examined county-level data on all injury deaths across the U.S. from 1999-2006 (because of their unusual nature, deaths from the 9-11 terrorist attacks were excluded).Findings from the study support prior work showing that overall homicide rates are lower in rural areas than urban areas. This was found to be true in all age groups, except the oldest adults (over 65 years old). Suicide rates, on the other hand, showed an increase with rurality, but the increased rate of suicide death in rural areas only reached statistical significance for the two youngest age groups: 0-14 years and 15-19 years.However, the magnitude of homicide- and suicide-related deaths, even in urban areas, is far outweighed by the magnitude of unintentional-injury deaths — such as those from car crashes and falls — in nonurban areas, especially in rural areas. Specifically, the rate of unintentional-injury death is over 15 times that of homicide for the entire population and the risk of unintentional-injury death is 40 percent higher in the nation’s most rural counties compared to the most urban.The research team found that the bulk of unintentional injury deaths result from motor vehicle crashes, with motor vehicle injury-related deaths occurring at a rate that is more than 1.4 times higher than the next leading mechanism of injury death. In rural areas, this difference is even more pronounced, where motor vehicle injury-related death rates are twice that of the next leading injury mechanism. …

Read more

Rare immune cells promote food-induced allergic inflammation in the esophagus

July 22, 2013 — Food is an integral part of life; but, for some, it can be harmful. Allergic inflammation caused by inappropriate immune responses to some types of food has become a major public health issue. Over the past ten years, the prevalence of food allergies has increased by nearly 20 percent, affecting an estimated six million people in the U.S.Eosinophilic esophagitis (EoE) is a food allergy-associated disease that affects children and adults and is caused by inflammation in response to such trigger foods as eggs, nuts, milk, wheat, and soy. Inflammation of the esophagus, as seen in EoE patients, can eventually lead to debilitating esophageal dysfunction, causing difficulty in swallowing, esophageal fibrosis, and food impaction. However, current treatment options for EoE, including adherence to strict diets, are non-specific and disruptive to patients’ lifestyle.Until recently, the mechanisms underlying the development of EoE were unclear, but a new study from the Perelman School of Medicine at the University of Pennsylvania and The Children’s Hospital of Philadelphia (CHOP) shows that a type of rare immune cell and specific reactions to allergenic foods team up — in a bad way — to cause EoE. However, this association does point to new ways to possibly treat inflammation associated with EoE.The presence of large populations of immune cells in the esophagus of human patients with EoE suggests that the immune system might contribute to the pathogenesis of this disease. In earlier work, researchers from CHOP, along with collaborators at Cincinnati Children’s Hospital, found that genetic mutations in the gene that encodes for thymic stromal lymphopoietin (TSLP), a protein that is produced by epithelial cells that line the esophagus and directs the activities of various types of immune cells, are highly associated with EoE in children. These results suggested that TSLP played an important role in the development of this disease, but how this factor contributed to esophageal inflammation in response to food was unknown.Now, David Artis, PhD, associate professor of Microbiology at Penn, two postdoctoral researchers in the Artis lab, Mario Noti, PhD and Elia Tait Wojno, PhD, and colleagues, have identified one mechanism by which TSLP might contribute to the development of EoE. They describe their work this week online ahead of print in Nature Medicine.Using a mouse model of EoE, Artis’s group found that sensitization to egg and peanut protein, in association with increased levels of TSLP, led to the mobilization of a rare type of immune cell called basophils. In healthy people, these cells comprise less than 1 percent of the total immune cells in the body. …

Read more

Utilizzando il sito, accetti l'utilizzo dei cookie da parte nostra. maggiori informazioni

The cookie settings on this website are set to "allow cookies" to give you the best browsing experience possible. If you continue to use this website without changing your cookie settings or you click "Accept" below then you are consenting to this.

Close