Monthly Archives: July 2013

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During a walk in a past autumn, Mikala Egeblad noticed a red leaf on the ground, surrounded by green leaves.

“It was very striking,” she said. “My first thought when I saw that was, ‘if only you could see the first cancer cells, to have them stand out.’”

Egeblad’s observation stems from her research, where the assistant professor at the picturesque not-for-profit Cold Spring Harbor Laboratory dedicates her working hours to studying the tumor microenvironment (the cells and material around a tumor) for pancreatic and breast cancers.

“The cancer cell is not alone,” said Egeblad. “It needs a support network. That comes from the body’s normal cells. The tumor is hijacking [those other cells] to fit its needs. Our idea is to try to take away the support line.”

Originally from Denmark, Egeblad likened her approach to the way the Danish Resistance fought the occupying army from Germany in World War II. Recognizing that they were unlikely to defeat the Germans head on, they disrupted trains and sabotaged factories.

Similarly, Egeblad is exploring ways to prevent tumors from corrupting nearby supporting cells. She wants to block the signals the tumors send out and prevent the microenvironment from receiving those malevolent cellular instructions.

Last year, she helped discover that inhibition of a receiver for chemokines (a chemokine receptor) in the tumor microenvironment makes breast cancer more responsive to chemotherapy.

She has also looked specifically for molecules that are different between normal and hijacked cells in fibroblasts or secreted by fibroblasts. Fibroblasts are cells that help provide a structural framework for tissues by secreting fibers and other substances.

She is collaborating on this research with Scott Powers, another scientist at CSHL. Using fluorescent proteins modified from those expressed by jellyfish, she can also see how fibroblasts and immune cells move around and interact. Seeing how these cells move, or whether they stop, she said, provides insights into what they do.

In cell cultures (i.e., not in live subjects), factors she adds from bacteria can enhance the immune cell’s ability to kill tumor cells. The activated immune cells can kill 90% of the breast or pancreatic cells from advanced tumors. She is focusing on understanding why the last 10% are not killed, because she thinks this is the key to get the method to work in tumors, where it currently is ineffective.

A researcher who wants to see how cancers work, Egeblad co-developed a spinning disk confocal microscopy system in which she can observe live cancers in action in mice.

Egeblad’s collaborators praised her work and her dedication.

Calling Egeblad a “rising star in cancer research with an international reputation,” Andrew Ewald, an assistant professor at Johns Hopkins, has worked with the CSHL scientist for over five years.

Egeblad came to scientific research through medicine. She was originally planning to become a doctor. As part of her medical training, she worked in a lab where she explored how things worked in relation to disease.

She decided she wanted to “understand how these diseases are developing” and wanted to try to “find new approaches to stop diseases.”

The fight against cancer is personal for Egeblad, whose grandmothers died from breast cancer and glioblastoma.

Egeblad has “chosen hard problems and understood they’d be difficult to solve,” Ewald said. “She has worked tirelessly and relentlessly to solve them anyway, with a great deal of success.”

Ewald said his collaborator has approached her work with a passion to “improve patient outcomes. The faster we can go, the more people we can help.”

A resident of Cold Spring Harbor, Egeblad lives with her long-term partner and their young daughter. Growing up in northern Copenhagen, she found some similarities to her home landscape. From the coastline of Copenhagen, residents can see Sweden. Standing on the shores of Long Island, she can view Connecticut.

As for her lab, her longer term interest is to understand the communication that goes on between cancer and normal cells.

“I want to know if communications between cancer cells and cells in the microenvironment changes the fate of the cancer cells in the long term,” she suggested. She is particularly interested in whether a tumor relapses years after an apparent cure.

 

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Nature has become a master builder, creating shells that blend an ability to resist wearing away by salt water and predators, with a beauty that the world’s best painters regularly try to emulate.

Scientists like Elaine DiMasi at Brookhaven National Laboratory are working to understand these natural manufacturing processes that may one day play a role in future innovations.

Using the National Synchrotron Light Source at BNL, DiMasi has studied the molecular steps in the so-called biomineralization process. Biomineralization usually hardens or stiffens tissues, although it can have other applications, including some that are detrimental to health, such as kidney stones.

“The question is how much can be mimicked without being an organism,” she said, of understanding and copying the steps that produce some of nature’s most durable material. “There are a lot of people who are well-motivated and funded who are trying to figure out the trick on the chemistry end.”

DiMasi, who earned her Ph.D. in physics from the University of Michigan in Ann Arbor, has put her own research on the back burner as she works on enhancing scientists’ ability to see these steps through the planning and refinement of the NSLS-II. The new light source, which is expected to be completed in 2015, will produce X-rays that are 10,000 times brighter than its predecessor, which was built in 1982.

DiMasi said she has gone through numerous meetings where she participates in discussions about the design optics. She said she’s learning some of the details on the fly and that it’s been “a pleasure to study and learn something new.”

While working on the NSLS-II, DiMasi recently finished co-editing a handbook called “Biomineralization Sourcebook: Characterization of Biominerals and Biomimetic Materials,” which is due out next March.

“That’s a big weight off my shoulders,” she said.

DiMasi said the book’s audience could include nontechnical readers because some of the chapters in the 600-page book include history.

In one chapter, the book examines naturalist drawings that are 100 to 200 years old and compares them to photographs.

Laurie Gower, an associate professor at the University of Florida in the Materials Science and Engineering department, said she originally recruited DiMasi to co-edit the book. DiMasi, however, wound up doing more than half the work, Gower said, because of when the contributors submitted their chapters.

DiMasi is looking forward to future collaborations at the NSLS-II. One of her roles is to understand how the molecules connect in long range order to make a thread or sheath. She said her work can also explore the different chemical compositions in different places in biological materials.

“Our measurements could show what molecular material it was,” she said. “It could show that one place was harder or one place was more or less dense. We could see the chemical composition or crystal structure.”

“There are some inspirations from biomineralization already,” she said. “Bone is constantly broken up and dissolved by cells.” When people exercise, pieces of mineral break down, which “sends a signal to regurgitate new materials.”

A resident of Miller Place, DiMasi said she grew up with “National Geographic” magazines, encyclopedias and a healthy dose of curiosity.

“One time,” she said, “I got into an argument with my dad. He was speculating how the system of the eyeball worked. I went off to check a book and I overheard my dad say, ‘She’s trying to prove me wrong.’ I particularly enjoyed overhearing Mom reply, ‘and she will because you are wrong.’”

A keyboard player, songwriter and arranger, DiMasi is a member of a band called Indulgent Lucie, which mixes pop and reggae combinations. DiMasi, who plays the oboe and English horn, celebrated completing the book by taking an online music class.

Gower said DiMasi, who has a strong reputation in the world of biomineralization, has impressed her with her adventurous spirit.

“She drove across the country” with her dog, Gower said. “She’s very independent.”

As for her work, DiMasi said she’s excited by the constant struggle to understand natural processes.

“It’s one thing to mimic the shell layers of an organic material,” she said. “It’s another to know what is deposited, step by step, when an organism is growing.”

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Preventing and controlling COPD symptoms

By David Dunaief, M.D.

COPD, or chronic obstructive pulmonary disease, is the third leading cause of mortality in the United States (Natl Vital Stat Rep. 2011 Dec.;59(10):1-126), although it’s not highlighted much in the layman’s press.

COPD is an umbrella term that includes emphysema, chronic bronchitis of more than three months for two consecutive years and/or chronic obstructive asthma. It is an obstructive lung disease that limits airflow. The three most common symptoms of the disease involve shortness of breath, especially on exertion, production of sputum and cough. This disease affects greater than 5% of the U.S. population (MMWR Morb Mortal Wkly Rep. 2012;61:938).

It tends to be progressive, meaning more frequent and severe exacerbations over time. Since it is a devastating and debilitating chronic disease with no cure, anything that can identify and prevent COPD exacerbations, as well as comorbidities (associated diseases), is critically important.

What are the traditional ways to reduce risk of and treat COPD exacerbations? The most important step is to stop smoking, since 80% of COPD is related to smoking. Supplemental oxygen therapy and medications, such as corticosteroids, bronchodilators (beta-adrenergic agonists and anticholinergics) and antibiotics help to alleviate symptoms (N Engl J Med. 2002;346:988-994).

One of the underlying components of COPD may be chronic inflammation (www.goldcopd.org). Therefore, reducing inflammation may help to stem COPD exacerbations. There are several inflammatory biomarkers that could potentially help predict exacerbations and mortality associated with this disease, such as interleukin-6 (IL-6), C-reactive protein (CRP), leukocyte (white blood cell) count and fibrinogen (a clotting factor of the blood).

Some drugs, such as statins, work partially by reducing inflammation. They may have a role in COPD. Lifestyle changes that include a high-nutrient, anti-inflammatory diet and exercise may also be beneficial.

 

Biomarkers for inflammation

In a recent population-based study with over 60,000 participants, results show that as three biomarkers (CRP, leukocyte count and fibrinogen) were elevated, the risk of COPD exacerbation increased in a linear manner (JAMA. 2013;309:2353-2361). In other words, the risk of frequent exacerbation increased 20%, 70% and 270% within the first year as the number of elevated biomarkers increased from one to three, compared to patients who did not have biomarker elevations.

As time progressed beyond the first year of follow-up, risk exacerbation continued to stay high. Patients with all three biomarkers elevated for longer periods had a 150% increased risk of frequent exacerbations. These predictions were applicable to patients with stable and with mild COPD.

In an observational study, results showed that when the biomarker interleukin-6 (IL-6) was elevated at the start of the trial in stable COPD patients, the risk of mortality increased by almost 2.7-fold (Respiratory Research. 2013;14:24). Also, after three years, IL-6 increased significantly. Elevated IL-6 was associated with a worsening of six-minute walking distance, a parameter tied to poor physical performance in COPD patients. However, unlike the previous study, CRP did not show correlation with increased COPD exacerbation risk. This was a small trial, only involving 53 patients. Therefore, the results are preliminary.

These biomarker trials are exciting for their potential to shape treatments based on level of exacerbation risk and mortality, creating more individualized therapies. Their results need to be confirmed in a randomized controlled trial (RCT). Many of these biomarkers mentioned in the two trials are identifiable with simple blood tests at major labs.

 

Statin Effect

Statins have been maligned for their side effects, but their efficacy has been their strong suit. An observational trial showed that statins led to at least a 30% reduction in the risk of COPD exacerbations, with the effect based on a dose-dependent curve (Am J Med. 2013 Jul;126:598-606). In other words, as the dose increased, so did the benefit.

Interestingly, even those who had taken the statin previously saw a significant reduction in COPD exacerbation risk. The duration of statin use was not important; a short use of statins, whether presently or previously, had substantial benefit. However, the greatest benefit was seen in those who had been on a medium to high dose or were on the drug currently. The researchers believe that the mechanism of action for statins in this setting has to do with their anti-inflammatory and immune-modulating effects. This was a retrospective (backward-looking) study with over 14,000 participants. We will need a prospective (forward-looking) study and RCT to confirm the results.

 

Exercise

Exercise is beneficial for almost every circumstance, and COPD is no exception. But did you know that a pedometer might improve results? In a three-month study, those with mild COPD were much more successful at achieving exercise goals and reducing exacerbations and symptoms, when they used pedometers, compared to the group given advice alone (ATS 2013 International Conference: Abstract A1360). Pedometers gave patients objective feedback on their level of physical activity, which helped motivate them to achieve the goal of walking 9,000 steps daily.

When exercising, we are told to vary our exercise routines on regular basis. One study demonstrates that this may be especially important for COPD patients (Am J Respir Crit Care Med. 2013; online Feb. 28). Results show that nonlinear periodization exercise training is better than traditional routines of endurance and resistance training in severe COPD patients. The goal of NLPE is to regularly alter the time spent working out, the number of sets, the number of repetitions and the intensity of the workout.

This study was randomized, involved 110 patients, and was three months in duration. Significantly more severe COPD patients achieved their exercise goals using NLPE than the traditional approach. The group that used NLPE also had an improved quality of life response. The researchers believe that compliance with an NLPE-type program is mostly likely going to be greater because patients seem to enjoy it more.

Nonspecific inflammatory biomarkers are potentially valuable for providing more personalized approach to therapy. Drugs that can control inflammation, such as statins, show promise. But don’t forget the importance of lifestyle changes, such as quitting smoking and committing to an exercise regimen that is varied and/or involves the use of a pedometer. And potentially a high-nutrient, anti-inflammatory diet will also contribute positively to reducing the frequency and severity of COPD exacerbations.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

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Study shows no benefit with fish oil

Age-related macular degeneration (AMD) remains the leading cause of central vision loss or severe visual impairment in patients over the age of 65 (Ophthalmology. 2008;115:116–126). In fact, advanced AMD is the cause of greater than half of severe vision impairment in the U.S. (Arch Ophthalmol. 2004;122:477-485). There are several stages of the disease: early-stage, or dry; intermediate; and advanced (either geographic atrophy or wet) AMD.

Fortunately, there are drugs that help treat the vision loss, and options are expanding. These involve vascular endothelial growth factors, including ranibizumab, off-label bevacizumab and the newest, aflibercept. There is also a combination drug therapy in development that may improve vision further; it involves the current medications, plus a potential new class, a platelet-derived growth factor (PDGF) inhibitor.

However, there is no cure for AMD. In fact, there is no treatment for the early, or dry, form of AMD. Therefore, identifying factors that may help decrease the risk of progression to advanced disease should be front and center. The goal of the Age-Related Eye Disease Study 2 (AREDS2) was just this – to reduce progression by identifying the optimal supplement formulation.

Just as important is identifying factors that may increase overall risk of developing AMD. We know that smoking, family history and age are contributing factors, and potentially iron (Am J Epidemiol. 2009;169:867-876). In addition, sunlight may play a role. Also, there have been three recent studies with conflicting results regarding aspirin’s potential to raise AMD risk.

Let’s look at the evidence.

 

Age-Related Eye Disease Study 2

The purpose of AREDS2 was to improve a multivitamin identified in the original AREDS study that illustrated a 25 percent reduction in progression from early-stage to advanced AMD. The multivitamin was composed of zinc, copper, beta-carotene and vitamins C and E, all considered to enhance antioxidant defenses.

AREDS2 researchers compared multiple formulations of the original AREDS multivitamin, adding omega-3 fatty acids — fish oil including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) — and/or lutein/zeaxanthin. They also compared variations with and without beta-carotene. In this randomized controlled trial (RCT), the gold standard of studies, the results with fish oil were disappointing (JAMA. 2013;309:2005-2015). There was no risk reduction — a stark contrast to an observational study I mentioned in my May 3, 2011 article. RCTs always trump observational trials.

AREDS2 showed a modest decrease in risk with lutein/zeaxanthin in a certain population. Beta-carotene deletion decreased the risk of lung cancer, mostly in previous smokers, but it did not affect progression to late AMD. It may also have had a role in preventing the absorption of lutein/zeaxanthin.

The lutein/zeaxanthin group saw an additional 5 percent reduction in risk in the group that had the lowest levels of these compounds from their diet at the trial’s start. Those patients who ate more foods with lutein and zeaxanthin, such as green, leafy vegetables and red, orange and yellow fruits and vegetables, did not see this small but significant beneficial effect. The reason may be that the patients eating a higher nutrient-dense diet already have sufficient levels of lutein and zeaxanthin. The duration of AREDS2 was five years and involved 4203 AMD patients between 50 to 85 years of age with the possibility of progression to advanced disease.

 

Aspirin effect conflicting

It is essential to discuss the role of aspirin, since approximately 20 percent of patients take this drug on a chronic basis (ahrq.gov). There are three recent studies: two were observational and one meta-analysis included observational studies. As I mentioned, observational studies are not the best types of studies.

In the Beaver Dam Eye Study, results showed there was a significant, yet small, increased risk of developing advanced, but not early-stage, AMD when taking aspirin (JAMA. 2012;308:2469-2478). The data can be subdivided even further: those with advanced AMD – neovascular (wet) and geographic atrophy groups – saw vastly different results, with increased risk for the former and decreased risk for the latter. Negative effects only occurred if patients had been taking aspirin for at least 10 years. Those at the five-year mark did not see a difference compared to nonusers. Chronic use was defined as at least two times weekly. Aspirin dosage did not have any impact.

In a second study, aspirin was associated with an increased risk of early AMD (Br J Ophthalmol. 2013 June;97:785-788). However, it became nonsignificant when patients with cardiovascular disease were factored into the mix. The authors concluded that there was no association, though caution and further study may be needed of patients who have cardiovascular disease and take aspirin, which make up a substantial number of aspirin users.

In the third and most recent study, a meta-analysis (group of 10 studies), there was no association between aspirin use and AMD. Risk levels were the same in early and advanced disease. The moral of the story is to speak with your doctor when considering taking aspirin if you have AMD.

 

Rosemary extract

On a more upbeat note, it seems that rosemary extract or oil plus zinc decreases the risk of developing retinal damage in rats that is similar to advanced AMD (Molecular Vision. 2013;19:1433-1445).Rats were exposed to damaging lights to try to induce detrimental effects. Zinc alone and rosemary alone were not nearly as effective as the combination. These two substances together decreased the damaging effects of the green light to the retina (back of the eye). Interestingly, the current AREDS multivitamin was not found to be as beneficial as the combination of zinc and rosemary. These are encouraging possibilities for a multivitamin of the future that prevents AMD progression.

We know that aspirin’s benefit outweighs its risk in cardiovascular disease; therefore, do not consider stopping aspirin until talking to your physician. Until well-designed RCTs are done, it is not clear that aspirin elevates AMD risk.

Unfortunately, the ideal formulation for a multivitamin to prevent AMD progression has not been perfected. The AREDS2 formulation with the addition of lutein/zeaxanthin and the deletion of beta-carotene is not commercially available yet. If you don’t have a smoking history, then taking the original AREDS multivitamin formulation is beneficial, plus lutein/zeaxanthin or foods containing these substances. However, if you do smoke, you may want to talk to your doctor about using the AREDS formulation that contains lutein instead of beta-carotene.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to www.medicalcompassmd.com and/or consult your personal physician.

 

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While tourists cruised along the Alaska coastline in June to see whales, sled dogs and glaciers, Carl Safina journeyed by boat through some of the state’s less-traveled regions in search of garbage.

The acclaimed author, ecologist and Stony Brook research professor joined a crew for a project called Gyre. The trip enabled participants to witness the trash that litters the shoreline, threatening wildlife.

The Gyre project, named for the rotating ocean currents, also included artists who collected trash they will use as part of a traveling art exhibition.

“It’s mainly a visibility raising effort,” said Safina, a MacArthur “genius” fellowship recipient. “It’s a way of showing people that, not only is garbage a problem where people live, but it is also a problem where animals live and where people go for natural beauty.”

While the waste in Alaska included consumer items like plastics that he sees near his Amagansett home, it also had more industrial pieces, including commercial fishing and shipping gear.

“There appears to be little concerted effort to find and track down the origin of this stuff,” Safina said. “Is it an accident or is it being dumped? A larger portion of the effort should go towards eliminating the problem.”

The Gyre team removed about four tons of trash.

Still, as he tends to do in his books, which include “Song for the Blue Ocean” and “Eye of the Albatross,” Safina didn’t fixate on the negative during his Alaska trip.

There was less and different trash than he was expecting, he said. The trash also seemed to collect in protected, calmer areas, unable to cling to the faster moving water near more dynamic cliffs.

He reveled in the opportunity to observe a grizzly bear with her three cubs for over an hour. The bear came within 20 yards of the group.

“I have enough experience with wildlife to have a sense that she was completely relaxed,” he said. “I love the proximity of it.”

Safina said the trip didn’t come at a particularly good time for him, because he is researching and writing his latest book, which is about the cognitive experiences of animals.

“This project was important enough to be worth that interruption,” he said.

While Safina has lobbied to protect the environment, helping to pass a United Nations Global Fisheries Treaty, he has transitioned to being more of a writer and witness.

“I was a plaintiff” on lawsuits in the 1990s, he said. “I hope what I do [now] inspires other people to do the kinds of things I was doing.”

Hope is an important part of his passion.

“He points out all the things that are wrong with what we do, but his final take on everything, his final philosophy, is a positive one,” said Jean Naggar, Safina’s literary agent at her eponymous agency.

A co-chair for the steering committee for the Alan Alda Center for Communicating Science, Safina teaches a course for graduate students.

“He’s a great example of a person who can interweave factual material with an ability to tell memorable stories,” Elizabeth Bass, the director of the center. He is a “very inspirational figure” for his students.

Safina blends science with art, Bass said. A percussionist who worked his way through the State University of New York at Purchase playing drums, Safina mixes an appreciation for nature and the environment with disappointment, frustration and a call to action.

“Not many scientists are comfortable talking about beauty in the way that [he] is,” said Bass.

In a class they teach together, Safina and Bass challenge students to think about their audience, asking them to define gravity in a lecture or by telling a story.

Safina, who hosts a PBS series, “Saving the Ocean with Carl Safina,” lives with his partner Patricia Paladines, who works as a program officer at Centre ValBio, a Stony Brook research facility. An avid fisherman, Safina rarely orders anything from a restaurant if he has to worry about its origin.

“The last time I had clams,” he said, “I dug them myself.”

Naggar, who admires his “lyrical” writing and calls him a “scientist with a heart,” said she has become more careful about restaurant fish, too.

As for his work, Safina said most people look at a bird or a deer and think of those animals as not other than people. “I see them really quite a lot like I see other people.”

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People travel to escape from their routines and desk jobs to the world where Christopher Paparo works. He routinely ventures in and around waters on the East End of Long Island that are filled with seal, dolphins, sharks, humpback whales and even an occasional octopus. The naturalist, who was a senior aquarist for the Long Island Aquarium for 13 years, recently got a new job: he is the director of the new $8.5 million Marine Sciences Center in Southampton.

“As a former Long Island University student, it’s amazing to see what’s transpired here,” said Paparo, who was just getting his feet wet in his new post. “What’s being built is amazing.”

The new center provides research facilities for graduate students, undergraduates and scientists, and will open officially in September. Notable guests at the grand opening are expected to include Stony Brook President Samuel Stanley, Senator Ken LaValle (R-Port Jefferson) and Assemblyman Fred Thiele (I-Sag Harbor). The 15,000-square-foot building is the latest resource for the School of Marine and Atmospheric Sciences.

“I’ll be wearing many, many hats,” said Paparo, who is known on the East End as a naturalist and the “Fish Guy” for wide-ranging photos of seals, sea lions, starfish and butterflies, among others, that make Long Island look like a “National Geographic” destination.

One of his first jobs is making sure the seawater system is up and running and maintained properly. He has to prepare tanks for researchers.

“A facility like this will allow us to grow and will make it a more attractive facility for researchers studying from other universities,” he said. “They can come here and work in a field station. It’s a world class facility to do their research.”

At the same time, he will help Lecturer Kurt Bretsch build out the “Semester at Sea” program, which is a three-year-old undergraduate effort. That program offers courses on Long Island marine habitats, which allows students to immerse themselves in the Shinnecock Bay, Atlantic Ocean and Great Peconic Bay. Another course emphasizes the maritime traditions of New York and New England.

Paparo can also accompany any group that needs a naturalist to explain what Long Island waters have and, if they decide to go on a boat ride, to show them what they’re seeing.

He said he’s “pretty flexible” about the kinds of tours he gives. For an ecology course, for example, he might take a group out to Shinnecock Bay, where he would compare the fish they catch by trawling over an eelgrass bed with those that live in a sandbar.

Classes have to pay a fee to cover the cost of the trip. Interested teachers or educators can contact SoMAS to ask about such trips.

The wet room at the Marine Sciences Center has a hallway of glass windows, which will allow visitors to watch researchers conduct their experiments on sea grass, shellfish and fish. The center will house modern molecular, remote detection and bioinformatic technology.

“My goal” as the first director of the new center “is to bring awareness to the community. Let them know what’s in their backyard,” said Paparo.

During trips into the water, he’s been surprised that people are so fascinated with sea horses. “Some people think they are mystical,” Paparo said. “We have a lot of them in the local bays.” Octopi, while not common, also live in the waters off Long Island.

Paparo and his wife Candy, the assistant director of animal training at the Long Island Aquarium, live in Calverton.

Everyone assumes, Paparo said, that animal training and working with marine mammals are glamorous jobs.

“Glamour is a small part of it. People don’t see the hours of cleaning, prepping and scrubbing. There’s a lot of work that goes into it for the 15-minute show.”

Paparo cautioned that those captive well-trained animals also can have a “bad day” and that all animals, even the cute, cuddly ones, can be dangerous.

Years ago, he responded to a call about a grey seal pup stranded on a beach. The woman who asked for help from the rescue program was getting too close. When he arrived and brought the seal back to the water, it bit him, growled and reacted the way he would have expected from an animal that felt threatened.

Still, he said working with and appreciating these animals and their environment is well worth the Friday night pipe fixes that keep the animals in his charge alive and the scars from difficult rescues.

“It’s awesome and very rewarding,” he said. “That’s what keeps us doing it.”

As a part of a monthly lecture series, Paparo is giving a free talk titled “Underwater Journey of Long Island Through the Eyes of a Fishing Biologist” at Duke Lecture Hall at 239 Montauk Highway in Southampton at 7:30 pm on Oct. 4.

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Refined carbs may cause food addiction

Hunger is only one reason we eat. There are many psychological and physiological factors that influence our eating behavior, including addictions, lack of sleep, stress, environment, hormones and others. This can make weight management or weight loss for the majority who are overweight or obese — approximately 70 percent of the U.S. population — very difficult to achieve (www.cdc.gov).

A June 29 New York Times article, entitled “Why Healthy Eaters Fall for Fries,” reported on the effect of posting food calories in New York City chain restaurants. Unfortunately, the results were mostly abysmal, with only a few exceptions; there was either no change or even an increase in calorie intake, when researchers examined customers receipts.

Does this mean we are doomed to acquiesce to temptation? Actually, no: It is not solely about willpower. Changing diet composition is more important.

What can be done to improve the situation? In my experience in my practice, increasing the quality of food has a tremendous impact. Foods that are the most micronutrient dense, such as plant-based foods, rather than those that are solely focused on macronutrient density, such as protein, carbohydrates and fats, tend to be the most satisfying. In a week to a few months, one of the first things patients notice is a significant reduction in their cravings. But don’t take my word for it. Let’s look at the evidence.

Effect of refined carbohydrates

By this point, many of us know that refined carbohydrates are not beneficial. Well, there is a new randomized controlled trial, the gold standard of studies, with results that show refined carbohydrates may cause food addiction (Am J Clin Nutr Online 2013;Jun 26). There are certain sections of the brain involved in cravings and reward that are affected by high glycemic (sugar) foods, as shown by MRI scans of participants.

The participants consumed a 500-calorie shake with either a high glycemic index or with a low glycemic index. The participants were blinded (unaware) to which type they were drinking. The ones who drank the high glycemic shake had higher levels of glucose in their blood initially, followed by a significant decline in glucose levels and increased hunger four hours later. In fact, the region of the brain that is related to addiction, the nucleus accumbens, showed a spike in activity with the high glycemic intake.

According to the authors, this effect may occur regardless of the number or quantity of calories consumed. Granted, this was a very small study, but it was well designed. High glycemic foods include carbohydrates, such as white flour, sugar and white potatoes. The conclusion: Everyone, but especially those trying to lose weight, should avoid refined carbohydrates. The composition of calories matters.

 

Comparing macronutrients

We tend to focus on macronutrients when looking at diets. These include protein, carbohydrates and fats, but are these the elements that have the most impact on weight loss? In a RCT, when comparing different macronutrient combinations, there was very little difference among groups, nor was there much success in helping obese patients reduce their weight (N Engl J Med 2009 Feb 26;360:859; N Engl J Med 2009 Feb 26; 360:923). In fact, only 15 percent of patients achieved a 10 percent reduction in weight after two years.

The four different macronutrient diet combinations involved an overall calorie restriction. In addition, each combination had either high protein, high fat; average protein, high fat; high protein, low fat; or low protein, low fat. Carbohydrates ranged from low to moderate (35 percent) in the first group to high (65 percent) in the last group. This was another relatively well-designed study, involving 811 participants with an average BMI of 33 kg/m2, which is defined as obesity (at least 30 kg/m2). Again, focusing primarily on macronutrient levels and calorie counts did very little to improve results.

Impact of obesity

In an epidemiological study looking at National Health and Nutrition Examination Survey data, results demonstrate that those who are overweight and obese tend to be lacking in micronutrients (Medscape General Medicine. 2006;8(4):59). The authors surmise that it may have to do with the change in metabolic activity associated with more fat tissue. These micronutrients include carotenoids, such as lutein, zeaxanthin, beta-carotene, alpha-carotene and beta-cryptoxanthin, as well as vitamin B12, folate and vitamins C, E and D.

However, it does not mean this population should take supplements to make up for the lack of micronutrients. Quite the contrary, micronutrients from supplements are not the same as those from foods. Overweight and obese patients may need some supplements, but first find out if your levels are low, and then see if changing your diet might raise these levels. With a few exceptions, such as vitamin D and potentially B12, most micronutrient levels can be raised without supplementation. Please ask your doctor.

Steroid levels

It may seem like there are numerous factors influencing weight loss, but the good news is that once people lose the weight, they may be able to continue to keep the weight off. In a recent prospective (forward-looking) study, results show that once obese patients lose the weight, the levels of cortisol metabolite excretion decreases significantly (Clin Endocrinol. 2013;78(5):700-705).

Why is this important? Cortisol is a glucocorticoid, which means it raises the level of glucose and is involved in mediating visceral or belly fat. This type of fat has been thought to coat internal organs, such as the liver, and result in nonalcoholic fatty liver disease. To learn more about this, please read my May 2 article. Decreasing the level of cortisol metabolite may also result in a lower propensity toward insulin resistance and may decrease the risk of cardiovascular mortality. This is an encouraging preliminary, yet small, study involving women.

Therefore, controlling or losing weight is not solely about willpower. Don’t use the calories on a menu as your sole criteria to determine what to eat; even if you choose lower calories, it may not get you to your goal. While calories may have an impact, the nutrient density of the food may be more important. Thus, those foods high in micronutrients may also play a significant role in reducing cravings, ultimately helping to manage weight.

 

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com and/or consult your personal physician.

Bailey brought comfort to personnel in Afghanistan

Bailey’s journey isn’t over yet, but she has found her home again after reuniting with Staff Sgt. Kevin Brady at the Save-A-Pet Animal Rescue and Adoption Center in Port Jefferson Station on July 4.

Fireworks popped in the distance as the Anatolian shepherd mix whined, wagged her tail and moved frantically around Brady, whom she had not seen in a couple of months.

The National Guardsman and his unit took in Bailey in the fall, when she was about eight weeks old. The dog had previously been tagging along with the Afghani army and the American unit quickly became attached to her. Brady, who recently finished his second tour, said she provided comfort to soldiers who were away from their kids, families and pets.

When the unit went back stateside, “Just leaving her there just didn’t seem right.”

That’s where the Guardians of Rescue came in. Dori Scofield, the group’s vice president as well as Save-A-Pet’s founder, said Brady contacted her three months ago about bringing Bailey to the United States. Guardians of Rescue, which rescues and finds homes for animals in need, raised $5,000 in nine days to help the soldier and “his battle buddy Bailey.”

Guardians of Rescue president Robert Misseri said Afghanistan can be a hostile environment for a dog, and when some people find a dog U.S. soldiers have left behind, they will kill it.

For all military personnel do for their country, “the least we can do is help them get their war buddy home,” Scofield said.

Staff Sgt. Kevin Brady is reunited with Bailey the dog, above, on Independence Day. Photo by Elana Glowatz
Staff Sgt. Kevin Brady is reunited with Bailey the dog, above, on Independence Day. Photo by Elana Glowatz

Nowzad, an organization that rescues dogs in Afghanistan, brought the dog to Kabul for her vaccinations and to get her spayed, she said. Bailey, who is now about 11 months old, made a stop at a kennel in Dubai before being shipped to John F. Kennedy International Airport. Scofield picked her up there on July 2.

“I walked into the cargo area and heard ‘Woof woof.’”

Scofield said Brady had been in constant contact with her and when she told him the dog was having a bath, he texted back, “She went from peasant to princess.”

Bailey waited at Save-A-Pet for a couple of days for her soldier to pick her up and take her with him on a road trip back to his home in Sacramento, Calif., where Brady has two sons.

The staff sergeant, who is still on active duty, is also a deputy sheriff in nearby Placer County.

Scofield said Bailey “loves everybody, but she’s looking for him.”

When Scofield brought Bailey outside to where Brady was waiting on the afternoon of July 4, she ran to her whistling friend and whined as he laughed and petted her.

“She got a lot bigger,” Brady said.

Bailey may have been unsure when she first went outside to be reunited with her buddy, Scofield said, but when Brady whistled to her, “you saw the light bulb go off in her head.”

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Dmitri Kharzeev’s work is hot. Indeed, the liquids he deals with are 100,000 times hotter than the interior of the sun.

Interested in the fundamental properties of matter, Kharzeev, a professor in the Department of Physics and Astronomy at Stony Brook and a senior scientist at Brookhaven National Laboratory, works at the Relativistic Heavy Ion Collider at BNL. There, he studies the so-called quark-gluon plasma. This primordial mixture is the most likely original soup from which life emerged in the moments after the Big Bang.

While Kharzeev looks closely at quarks, he has seen ways to apply his knowledge of chiral particles to an arena where heat can and is a problem: electronics.

When people put laptops on their laps, they can often feel the temperature of their microprocessors rising, making their laptops uncomfortably warm. The reason for this is that the transfer and processing of information in microprocessors generates heat, but the currents dissipate heat.

As it turns out, there are circumstances when the currents carried by chiral particles, like quarks, flow without any dissipation of heat. That is possible in the quark-gluon particles and in chiral materials, he explained.

Chirality is a state of handedness, in which a particle is not symmetrical. Kharzeev describes it as akin to a screw people can drive into a wall by turning its teeth either clockwise or counterclockwise to barrel through a substance.

“Chirality is the projection of angular momentum of a particle into its direction of motion,” he said.

When a quark approaches an impurity, it has to penetrate that barrier to conserve its chirality.

“When a chiral particle approaches a potential barrier, it penetrates it with 100% probability,” he said. “This is really a striking quantum phenomenon.”

Even further, the spin of a chiral particle is its nature, which means that it always moves and rotates. There is no rest state for it, the same way there is no rest state for light, he said.

“If, somehow, we were able to create chiral particles, not only in RHIC, but also in the materials around us, we could construct the next generation of electronic devices and we could solve a very big problem that mankind is facing,” Kharzeev said.

That problem is that the growth of the population of microprocessors, which consume energy, is faster than the growth in the human population.

That’s where graphene and substances like it enter the picture. Made of carbon atoms, the same way graphite and diamond are, graphene has electrons that behave as if they were chiral particles.

Kharzeev is a theoretical physicist. He is actively participating on the theory of chiral currents and that theory, he said, is being applied in chiral materials.

With the invention of graphene, “there is a gold rush,” he explained. “What is interesting for people like me is that the fundamental science and the applications are coming close together. People studying quarks could make research which could have an almost immediate practice application. This is very exciting and gratifying.”

Kharzeev said he got interested in graphene shortly after it was synthesized in the lab. Indeed, graphene has such potential that Andre Geim and Konstantin Novoselov at the University of Manchester received the Nobel Prize in Physics in 2010 for their groundbreaking work on it.

After reading one of their popular papers, Kharzeev realized “that, in many respects, graphene is similar to the quark-gluon plasma.”

Kharzeev recently received the Humboldt Research Award. The $80,000 award, which will allow him to work with German researchers at Goethe University in Frankfurt, among other places, is issued in Germany for scientific excellence.

“I am absolutely honored to receive this prize,” he said. “This is recognition of the work that we’ve been doing at Stony Brook and BNL for the past few years and I’m very excited for the new opportunities this prize offers.”

Jacobus Verbaarschot, a Stony Brook professor in the same department as Kharzeev who won the Humboldt Award in 2007, said he believes Kharzeev “deserves” the award, which is “good for the department.”

A resident of Port Jefferson, Kharzeev lives with his wife, Irina Sourikova, who is the database administrator of the PHENIX experiment at BNL.

Their older daughter, Maria, is an ICU nurse at the Memorial Hermann Hospital in Houston and plans to continue her education in an anesthesia school. Their younger daughter, Julia, is a student at Port Jefferson High School.

As for his research, Kharzeev is excited about the potential to contribute in a practical way to a significant challenge.

“The dissipation of heat now is the really major obstacle for electronics,” he said.

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While obesity has been thought of as a chronic disease by some, until recently, it was not officially recognized as such. Obesity impairs body function, with potentially negative impacts on physical activity and psychological well-being. It lines internal organs with fat, putting stress on the body; fat tissue may cause dysfunctional cell-signaling, potentially increasing inflammation in the body (Front Endocrinol (Lausanne). 2013 Jun 12;4:71).

The American Medical Association has taken an important step forward, declaring obesity a disease, unto itself. Obesity’s prevalence in the U.S. has increased by more than two-fold in the last two decades (JAMA 2010, 303(3):235-24). More than one-third of Americans are obese, defined as a body mass index of great than 30 kg/m2, according to the CDC.

The AMA’s move is a wake-up call that should be taken very seriously. They recognize that the first step to reversing this trend is increasing awareness among the medical community of its independent detrimental effects. This decision may impact government policy, medical reimbursement rates, and the social stigma patients have to withstand.

Unfortunately, obesity is also associated with many other chronic diseases. Integrative medicine physician Mark Hyman, M.D. entitled his book “Diabesity” to emphasize the association between diabetes and obesity. Other diseases associated with obesity include rheumatoid arthritis, cardiovascular disease, nonalcoholic fatty liver disease, osteoarthritis, and infection. I will discuss the RA association in more detail, since obesity was shown to potentially affect RA treatment.

Obesity treatment options include surgery, medications and lifestyle modifications. While it’s important for obese patients to lose weight, we have to be conscious about the way we do this. The drug Fen-phen, for instance, caused pulmonary hypertension and valvular heart disease. Surgery can potentially result in side effects, such as dumping syndrome and malabsorption. Even lifestyle modifications, including exercise and diet, need to be evaluated.

New launching of weight-loss drug

There are now two drugs approved by the FDA for weight-loss: Qsymia (phentermine hydrochloride/topiramate) and Belviq (lorcaserin). Both drugs have extensive side effects. Belviq was just recently launched in the United States (Medscape.com); however, it has not been approved by the European Union for fear of side effects, including tumors, disease of the heart valves and depression. It was also rejected by the FDA the first time because of its side-effect profile.

Effect on rheumatoid arthritis

On June 27 I wrote an article about RA, so I thought it appropriate to write about how RA is intertwined with obesity. A recent study found that greater than 50 percent of women who have RA are also obese (Arthritis Care Res (Hoboken). 2013;65(1):71-7). This was a cohort (those with disease compared to those without) study, involving over 1,400 participants. The reasons for this association may be underlying inflammation, greater amounts of estrogen or vitamin D deficiency. Obese men and women had a 24 percent increased risk of developing RA. The researchers are worried, since the prevalence of obesity in the general population continues to rise. This is not good news on the whole; women are more likely than men to develop RA, in general, according to a separate study (Ann Rheum Dis. 2007;66:1491-1496).

Obesity results in less robust outcomes when it comes to RA treatment. In an abstract presented at the European League Against Rheumatism Congress 2013, those who were obese had a two-fold greater risk of being on TNF (tumor necrosis factor) alpha inhibitors, compared to those who were of normal weight (BMI <25 kg/m2) (EULAR Congress 2013 Abstract OP0178). The researchers treated 346 RA patients with methotrexate plus or minus prednisone, but if they did not respond sufficiently, a TNF alpha inhibitor was added.

This occurred significantly more frequently with obese patients. Those who were obese had a less-than-ideal response to methotrexate plus or minus prednisone at a rate that was more than two times greater at 12 months than those of normal weight. Again, inflammation was postulated as the potential cause of poor response to the initial treatment in obese patients.

In yet another study, obese patients’ response to TNF alpha inhibitors was less robust compared to those who were not obese (Arthritis Care Res (Hoboken). 2013 Jan;65(1):94-100). At the end of the first year, remission rates of RA in obese patients were less than half those of normal patients. However, when the researchers analyzed the individual TNF alpha inhibitors, only Remicade’s (infliximab) poor response reached statistical significance, while the others were trending toward significance. This study involved 641 patients, but only 66 who were obese.

Let’s recap: patients with a history of obesity are twice as likely to develop RA and require TNF alpha inhibitors, but the effectiveness of these TNF inhibitors is reduced for them.

Lifestyle modifications

Lifestyle changes are critical to treating obesity; however, not all lifestyle modifications, including diet and exercise, are created equal. A recent study showed that those on a very low-calorie diet, or “crash diet,” were three times more likely to develop gallstones than those on a low-calorie diet (Int J Obes (Lond). Online 2013;May 22). The participants on the very low-calorie approach consumed liquid meals for 6 to 10 weeks, ingesting 500 calories per day, and then switched to a maintenance diet. The low-calorie group consumed liquid meals and solid foods totaling 1,200 to 1,500 calories per day for 12 weeks and then switched to a maintenance diet.

The reason for increased gallstones may be the impact of a very low-calorie diet on the bile’s composition and the gallbladder’s ability to discharge it. There were over 6,000 participants involved in the study. Thus, losing weight too rapidly is probably not the best approach.

In my experience, a high-nutrient, plant-based diet is one effective method for losing weight. I wrote about the quality of calories consumed, mindful eating and exercise in two articles published on Aug. 2, 2012 and April 30, 2013. I encourage you to read them, if you want to learn more about this topic.

Whether or not you agree with the AMA’s decision to elevate obesity to a chronic disease, it needs to be treated. Lifestyle modifications should be included in every paradigm, regardless of whether surgery or drugs are used as well. Some people may benefit from drug therapy, and some may benefit from surgery, but all will benefit from appropriate lifestyle modifications.

 

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, go to the website www.medicalcompassmd.com or consult your personal physician.

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