For preteen overweight girls, “pediatrically correct” literature may help normalize BMI.

DukeHealth.org - It’s no secret that reading is beneficial. But can it help kids lose weight? In the first study to look at the impact of literature on obese adolescents, researchers at Duke Children’s Hospital discovered that reading the right type of novel may make a difference.

The Duke researchers asked obese females ages 9 to 13 who were already in a comprehensive weight loss program to read an age-appropriate novel called Lake Rescue (Beacon Street Press). It was carefully crafted with the help of pediatric experts to include specific healthy lifestyle and weight management guidance, as well as positive messages and strong role models.

Six months later, the Duke researchers found the 31 girls who read Lake Rescue experienced a significant decrease in their BMI scores (-.71 percent) when compared to a control group of 14 girls who hadn’t (+.05 percent), explained Alexandra C. Russell, MD, a fourth-year medical student at Duke who led the study and presented the findings at the Obesity Society’s annual scientific meeting.

“As a pediatrician, I can’t count the number of times I tell parents to buy a book that might provide useful advice, yet I’ve never been able to point to research to back up my recommendations,” says Sarah Armstrong, MD, director of Duke’s Healthy Lifestyles Program where the research took place. “This is the first prospective interventional study that found literature can have a positive impact on healthy lifestyle changes in young girls.”

Obesity is becoming more prevalent in children, according to the CDC, which reports that 16 percent of children ages 6 to 19 are overweight or obese, a number that has tripled since 1980. Researchers are looking at a variety of ways to help kids stay healthy, lose weight and be more active, but Armstrong says, “most don’t work very well. The weight loss options that are effective typically involve taking powerful medications with side effects, or require permanent surgical procedures.”

While the BMI decrease attributed to the book is small, Armstrong says any decrease in BMI is encouraging because BMI typically increases in children as they grow and develop. That’s okay as long as it follows a normal, progressing curve. In overweight kids, however, BMI usually increases more rapidly. “If their BMI percentile goes down, it means they are they are either losing weight or getting tall and not gaining weight. Both are seen as positive indicators in kids who are trying to lose weight,” she explains.

The idea that a book can positively influence weight loss and decrease BMI is “encouraging because it’s fairly easy to implement,” she added. “And it’s a welcome addition to a world where there aren’t a lot of alternatives.”

When dining at Chinese Buffets, overweight Americans serve themselves and eat differently than normal weight individuals. This may lead them to overeat, according to a recent study by Cornell University’s Food and Brand Lab, and make it harder to lose weight. Compared to normal weight diners, overweight individuals sat 16 feet closer to the buffet, faced the food, used larger plates, ate with forks instead of chopsticks, and served themselves immediately instead of browsing the buffet.

“What’s crazy is that these people are generally unaware of what they’re doing – they’re unaware of sitting closer, facing the food, chewing less, and so on,” say Brian Wanink, lead author of this study and of the book “Mindless Eating: Why We Eat More Than We Think.”

The study was published in the journal Obesity and includes observations of 213 diners at 11 all-you-can-eat Chinese restaurant buffets across the country. Study participants included a range of normal weight to obese diners, none of whom were Asian. Major study findings include:

* 27 percent of normal-weight patrons faced the buffet compared to 42 percent of obese diners.
* Overweight diners sat an average of 16 feet closer than normal-weight diners.
* 16 percent of obese diners sat at a booth rather than a table compared to 38 percent of normal weight diners
* 71 percent of normal-weight diners browsed the buffet before serving themselves compared to 33 percent of obese diners
* 24 percent of normal-weight people used chopsticks compared with 9 percent of overweight people

“When food is more convenient people tend to eat more,” say coauthor Collin R. Payne, New Mexico State University.

“These seemingly subtle differences in behavior and environment may cause people to overeat without even realizing it” (Courtesy of EurekAlert!, a service of AAAS).

Harvard.edu - Many of us would like to firm up our waistlines, a goal that seems more frustrating and elusive the older we get. Working on strengthening a variety of trunk muscles, collectively known as “the core,” can help tone up abdominal muscles and much more, according to the October 2008 issue of Harvard Women’s Health Watch.

The core muscles - the muscles in the abdomen, lower back, and pelvis - lie roughly between the rib cage and the hips. The strength and coordination of these muscles is important not only for sports and fitness routines but also for daily life - for example, reaching up to a shelf, lifting a child, or sponging a spot off the floor.

Experts conclude from studies that well-coordinated core muscle use stabilizes the spine and helps create a firm base of support for virtually all movement. Exercises that strengthen abdominal and other core muscles should be part of an overall fitness plan that includes regular, moderate-intensity aerobic exercise. Guidelines also encourage us to get 20 to 30 minutes of strength training two to three times a week, and that might be a good time to fit in a few exercises designed to work the core.

Harvard Women’s Health Watch notes that in order to be safe and effective, core-strengthening exercises require proper alignment and progression from one type of exercise to another, adjusted to your body and fitness level. Anyone wishing to try core-strengthening exercises should work at a comfortable pace and avoid doing anything that causes pain.

WISC.edu - For the first time researchers have found a messaging system in the brain - NF-κB, or nuclear factor-kappa B - that directly affects food intake and body weight.

Reported in the October 3, 2008 issue of Cell, the findings (from a study in mice) point to a completely new approach to treating and preventing obesity in humans. The discovery also offers hope for new ways to treat related disorders, such as type 2 diabetes and cardiovascular diseases - the most prevalent health problems in the United States and the rest of the developed world.

Led by Dongsheng Cai, an assistant professor of physiology at the UW School of Medicine and Public Health, the researchers looked specifically at the hypothalamus - the brain structure responsible for maintaining a steady state in the body - and for the first time found that a cell-signaling pathway primarily associated with inflammation also influences the regulation of food intake. Stimulating the pathway led the animals to increase their energy consumption, while suppressing it helped them maintain normal food intake and body weight.

The research stems from recent explorations into the problem called metabolic inflammation, a by-product of too much food or energy consumption. Unlike the classical inflammation typically observed in infections, injuries and diseases such as cancer, the metabolic inflammation seen in obesity-related diseases is much milder, doesn’t lead to overt symptoms or cause tissues damage.

Metabolic inflammation is a chronic, low-grade condition consisting of inflammatory-like responses at the molecular level. It has many downstream consequences, says Cai. It causes cellular dysfunction, which can decrease the regulation of several physiological processes, including metabolism.

Scientists believe that metabolic inflammation may be at the core of many chronic, obesity-related metabolic disorders that are so common today, he adds.

Cai and his team zeroed in on NF-kappaB, a protein complex that can be activated specifically by IKKbeta to induce inflammatory reactions in many cell systems.

In earlier studies at Harvard, Cai and colleagues found that the pathway interrupted sugar, fat or protein metabolism in tissues where metabolism typically takes place - liver, fat and skeletal muscle. Feeding mice high-sugar and high-fat diets activated the pathway in these tissues.

Once he arrived at the SMPH three years ago, Cai began to consider whether metabolic inflammation might affect higher-up players in the central nervous system, particularly the hypothalamus. This brain structure is a critical master regulator of appetite and energy balance, and also controls metabolism in the peripheral tissues he had studied before. But nobody knew how the hypothalamus might contribute to the development of metabolic diseases such as obesity and diabetes.

We wanted to learn whether the pathway or pathways underlying metabolic inflammation could affect metabolism regulators in the central nervous system, he says.

In the current study, Cai and his team found first that IKKbeta/NF-kappaB does indeed exist in specific neurons in the hypothalamus. The pathway is much more abundant in the hypothalamus than in peripheral tissue, and it normally remains inactive in the brain.

The researchers next showed that over-nutrition through high-fat diet feeding activates IKKbeta/NF-kappaB, specifically in neurons in the hypothalamus.

When we knocked out the IKKbeta gene to suppress NF-kappaB activity in these neurons, the animals were significantly protected from energy over-consumption and obesity development, Cai says.

The researchers also examined a cell component called the endoplasmic reticulum (ER), shown recently to be involved in metabolic diseases involving over-nutrition, to see if it might play a role in linking over-nutrition to activate IKKbeta/NF-kappaB in the hypothalamus.

At the intracellular level, when the ER is challenged with over-nutrition, this leads to ER stress, which can push the IKKbeta/NF-kappaB pathway to an active state, although the involved reactions could be quite complicated, Cai says.

In several experiments, the researchers found that ER stress caused by over-nutrition activated IKKbeta/NF-kappaB in the hypothalamus. Suppressing ER stress in the central nervous system significantly preserved normal regulation of food intake and prevented obesity.

Cai says there is still a lot of work to be done. His group has begun studying IKKbeta/NF-kappaB connections to other pathways and regulations in the hypothalamus.

The ultimate goal will certainly be to identify a selective and effective suppressor of the pathway to target related neurons, he says, and hopefully find medications to help control appetite and obesity.

Jefferson.edu - A research team, led by investigators at the Department of Surgery at Jefferson Medical College of Thomas Jefferson University and the Kimmel Cancer Center at Jefferson, has achieved a substantial “kill” of pancreatic cancer cells by using nanoparticles to successfully deliver a deadly diphtheria toxin gene. The findings – set to be published in the October 2008 issue of Cancer Biology & Therapy – reflect the first time this unique strategy has been tested in pancreatic cancer cells, and the success seen offers promise for future pre-clinical animal studies, and possibly, a new clinical approach.

The researchers found that delivery of a diphtheria toxin gene inhibited a basic function of pancreatic tumor cells by over 95 percent, resulting in significant cell death of pancreatic cancer cells six days after a single treatment. They also demonstrated that the treatment targets only pancreatic cancer cells and leaves normal cells alone, thus providing a potential ‘therapeutic window.’ Further, they are targeting a molecule that is found in over three-quarters of pancreatic cancer patients.

“For the pancreatic cancer world, this is very exciting,” says the study’s lead author, molecular biologist Jonathan Brody, Ph.D. “There are no effective targeted treatments for pancreatic cancer, aside from surgery for which only a minority of patients qualify. We are in great need of translating the plethora of molecular information we know about this disease to novel therapeutic ideas.”

Pancreatic cancer is the fourth leading cause of cancer-related mortality in the U.S., reflecting the generally short survival time of patients - often less than a year from diagnosis.

This approach was originally developed in ovarian cancer cells by study co-author Janet Sawicki, Ph.D., a member of the Kimmel Cancer Center. She and her group had recent success in reducing the size of ovarian tumors following treatment with diphtheria toxin nanoparticles.

The strategy is based on the fact that both ovarian and pancreatic cancer cells significantly over-express a protein found on the cell membrane, called mesothelin. The function of that molecule is unknown, but it is found in the majority of pancreatic tumors and ovarian cancer tumors. Other solid tumors also express mesothelin, but not at such a high rate.

“We don’t know completely why cancer cells repeatedly turn on mesothelin genes to produce these membrane proteins, but it gives us a way to fool the cell and hijack its machinery, to trick it into making other more potent genes that will be detrimental to the cancer cells,” Brody says.

To do that, the researchers devised an agent that consists of a bit of mesothelin DNA connected to the gene that produces the toxin from diphtheria, a highly contagious and potentially deadly bacteria, which is now controlled through childhood DPT vaccination. “Naked” DNA is then coated in a polymer to form nanoparticles that are taken up by the cancer cells.

Inside the cells, the agent performs its trickery. The nanoparticles biodegrade and the cell machinery senses genetic material from mesothelin. It activates the diphtheria toxin gene, which then turns on production of the toxin which allows the toxin to then do its work on the cancer cells, Brody says. Within 24 hours of delivery, the toxin disrupted production of protein machinery by over 95 percent, and within six days, a number of cancer cells die or are arrested.

“The cancer thinks it is turning on mesothelin and once it gets started reading that genetic code, it can’t stop,” he says. “So it will read the bacteria’s DNA and produce the toxin which shuts down protein production in the cancer cells.”

“It worked well in our cell culture models and now we are moving into pre-clinical experiments,” Brody says.

The agent will not attack normal cells because the molecular machinery needed to turn on mesothelin is not found in normal cells, Brody says. Additionally, Sawicki has modified the diphtheria DNA to ensure that toxin that might be released from dying cancer cells is not taken up by healthy, normal cells.

But the researchers are now perfecting even more stringent measures to ensure safety, he says. “We can’t help being hopeful,” he says. “Our findings suggest that such a strategy will work in the clinical setting against the majority of pancreatic tumors.”

JAMA - Psychodynamic psychotherapy lasting for at least a year is effective and superior to shorter-term therapy for patients with complex mental disorders such as personality and chronic mental disorders, according to a meta-analysis published in the October 1, 2008 issue of JAMA.

Evidence indicates that short-term psychodynamic psychotherapy is insufficient for a considerable proportion of patients with complex mental disorders, i.e., patients with multiple or chronic mental disorders or personality disorders. Some studies suggest that long-term psychodynamic psychotherapy (LTPP) may be helpful for these patients. LTPP is therapy in which emphasis is placed on more interpretive or supportive interventions, depending on the patient’s needs, and that involves careful attention to the therapist-patient interaction.

Falk Leichsenring, D.Sc., of the University of Giessen, Germany, and Sven Rabung, Ph.D., of the University Medical Center Hamburg-Eppendorf, Hamburg, Germany, conducted a meta-analysis to examine the effectiveness of LTPP (lasting for at least a year, or 50 sessions) and whether it is superior to shorter psychotherapeutic treatments for complex mental disorders, including personality disorders, chronic mental disorders (defined as lasting at least a year) and multiple mental disorders. The researchers identified and included 23 studies for the meta-analysis (11 randomized controlled trials and 12 observational studies), involving a total of 1,053 patients receiving LTPP.

The authors found: “In this meta-analysis, LTPP was significantly superior to shorter-term methods of psychotherapy with regard to overall outcome, target problems, and personality functioning. Long-term psychodynamic psychotherapy yielded large and stable effect sizes in the treatment of patients with personality disorders, multiple mental disorders, and chronic mental disorders. The effect sizes for overall outcome increased significantly between end of therapy and follow-up.”

With regard to overall effectiveness, analysis indicated that after treatment with LTPP patients with complex mental disorders on average were better off than 96 percent of the patients in the comparison groups.

The authors add that further research should evaluate the cost-effectiveness of LTPP (JAMA 2008;300[13]:1551-1565).

In an accompanying editorial, Richard M. Glass, M.D., Deputy Editor, JAMA, and with the University of Chicago, commented on the findings regarding long-term psychodynamic psychotherapy.

“… the meta-analysis by Leichsenring and Rabung in this issue of JAMA provides evidence about the effectiveness of long-term dynamic psychotherapy for patients with complex mental disorders who often do not respond adequately to short-term interventions. It is ironic and disturbing that this occurs at a time when provision of psychotherapy by psychiatrists in the United States is declining significantly. The reasons for this merit careful evaluation. To some extent this may reflect the cost-efficacy of treatments for some mental disorders with medications and brief supportive visits. However, this trend appears to be strongly related to financial incentives and other pressures to minimize costs. Is that what is really wanted for patients with disabling disorders that could respond to more intensive treatment?” (JAMA 2008;300[13]:1587-1589).