Monthly Archives: May 2014

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The scent of a skunk, the familiar face of a friend, or the sound of shattering glass become part of a code that makes each of these stimuli familiar and recognizable almost immediately with each subsequent experience.

Glenn Turner, an associate professor at Cold Spring Harbor Laboratory, explores how one of the research world’s favorite test subjects, the fruit fly, develops a memory for smells.

“We can use a bunch of different techniques to understand how neurons in a memory center respond to different smells,” he said. “One of the things we found is that those neurons have really specific responses.”

Neurons, or the wiring cells that carry signals and affect everything from telling muscles to move to processing thoughts or activities, have such a highly specific signature that Turner can “easily tell the difference between when a fly smells a grapefruit and when it smells a lime.”

There is not, however, a universal signal in the brain of every fly, rat, monkey, or dolphin for certain senses. Each creature has a unique response to a sensory cue.

Turner said this is akin to a human’s response to the odor of durian, a fruit that smells like sweat socks. To those people who eat the fruit, the smell is appealing because they like the taste. Many people, however, react to the scent in the same way they would if they walked into an airless locker room after an overtime basketball game.

Thomas Clandinin, an associate professor of neurobiology at Stanford School of Medicine, who has known Turner for over two decades, described Turner’s work as “highly innovative.” Turner is “widely credited with being one of the people who made it possible to monitor neural activity in the fly, an approach that has really revolutionized fly neuroscience.”

Clandinin credits Turner with being “very good at teaching people how to use his approaches, magnifying the community impact.”
Recently, Turner conducted experiments in which he looked at the patterns of activity in the memory center of the fly’s brain to see if he could tell the difference between the neural signature of bananas and of apples. The goal was to see if the patterns were stimulus-specific so that they could account for the accuracy with which flies form memories.

The perceptual whole is “greater than the sum of the parts,” Turner said.

Fluorescence microscopy makes a protein in a cell increase in brightness whenever it is active. He used that technique to express individual neurons in a region of the fly’s brain called the mushroom body, to see what components of a smell cause the fly to react and interpret that smell.

“We were able to show that different individual synaptic sites have different tuning properties,” Turner said. “The only time the mushroom body signaled to its downstream partners was when several inputs were active at the same time.”

Flies have several input sites that are waiting for a smell to come along that they can process and understand. If the majority of the parts of a smell are consistent, the fly will process the chemicals in the air as that scent. If not, however, the fly may not react.

Another step in his research, he said, could be to determine what neurological changes occur in response to some learned connection. If, for example, a fly often smells the noxious fumes of paint thinner when he eats, he might process that signal in a way that’s different from a fly that is looking for a more conventional smell in the search for food.

One of the reasons the fly is an appealing subject for these studies is that there are mutant versions that don’t form memories. By studying these mutants, researchers like Turner can compare the neurological circuit of a fly that recognizes the smell of a banana from one that can’t.

Turner and his wife Lorraine Lew, a nutritionist who works at a renal dialysis clinic, got married last November. Turner enjoys hiking behind the Cold Spring Harbor Laboratory library and biking.

As for his research, Turner hopes his basic understanding of the way a fly interprets the information around it will have applications to other creatures.

“I would hope that one day, we will get a more concrete understanding of learning and memory,” he said.

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He creates materials that build themselves. By attaching parts that will connect in a specific way, he can build something that could be useful in fields ranging from harvesting energy, to advancing medical technology to offering clearer views in basic research.

Oleg Gang, a group leader in soft and bio-nanomaterials at the Center for Functional Nanomaterials at Brookhaven National Laboratory, is at the forefront of a field where the materials he’s trying to construct are about 1/1000th the width of a human hair.
At incredibly small scales, matter behaves in ways that are different from the world of apples falling from trees, cars slowing down on snowy roads, or baseballs flying over fences. Going from atoms to molecules to nanoparticles to large objects causes matter to change its properties due to the collective effects between atoms and the relative surface contribution, Gang explained.

Gang has been using something from another area of science for these self-assembled materials: DNA. The genetic blueprint that determines whether a cell becomes a part of a snail, a snake or a salmon has matching base pairs that make it a good candidate for construction. By attaching these DNA shells to small objects, Gang can encourage the pieces to come together on their own, as combinations of base pairs seek each other out, the way puzzle pieces floating in a dish might if they had a sequence of attachments that lined up in a specific order.

Extending the puzzle analogy, Gang has been able to put together two-dimensional structures. One of the many challenges facing him and others at Brookhaven, Harvard, Northwestern and a handful of other groups with similar research goals is figuring out how to generate three-dimensional structures.

Gang’s colleagues describe him as an innovator.

“The concepts he and a small number of other groups are pursuing represent an entirely new approach to constructing materials,” said Charles Black, a group leader in materials synthesis and characterization at the CFN. Gang is considered “an excellent scientist, making breakthrough discoveries while remaining careful in his work and sure of his scientific claims.”

Gang, who has several patents awarded with others pending, studies the basics of these self-assembly processes, hoping to understand more about how to build structures with more complex architecture.
He also takes requests from other scientists, who are looking to improve on existing products or who want to tap into his expertise to refine a product they already use.

He started his work with gold, but has now expanded to other classes of nanoparticles, including magnetic, catalytic, fluorescent and metallic.

Gang said he has helped improve various properties through self assembly. A few years ago, he said, he raised the light-emitting ability of a nanoparticle by a factor of five. That, he said, might prove useful in biodetection.

He also published results where he improved the ability of a detector to find the chirality, or spin, of particles, by a factor of 100.
Gang is developing research that will enable the structures he creates to transform to something else.

“A structure is the result of a particular interaction,” he said. “As soon as we change how the particles interact — they are not happy and are trying to find another configuration — they will change into something different.”

Gang said he benefits from working at the 7-year-old Center for Functional Nanomaterials, where he can not only work with a team of faculty fluent in the world of nanoscience, but where he can also collect additional information at the National Synchrotron Light Source and from electron microscopes.

Science, Gang said, often benefits by imitating nature. A plane, for example, isn’t a bird, although both can fly.

Gang believes his work is not at the early Leonardo DaVinci stage of flight, but is rather closer to the Wright Brothers, where he and other scientists can lift the plane off the ground, but can’t fly it yet.

Gang, who grew up in the western part of the Ukraine and then moved to Israel, now lives in Setauket with his wife, Alina, who works for a biodetection company in Medford. The couple’s 19-year-old daughter, Danielle is studying creative writing at SUNY Potsdam. They also have a 15-year-old son, Gabriel.

As for his work, Gang is excited about the prospects for contributing to science and society.

“We’re in a situation where many types of things become possible,” he said.

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Are there differences between heart attack symptoms for men and women?

Heart disease is the most common chronic disease in America. When we refer to heart disease, it is an umbrella term of which heart attacks are one component. Fortunately, the number of heart attacks has decreased over the last several decades, as have deaths from heart attacks. However, there are still 720,000 heart attacks every year, and more than two-thirds are first heart attacks (1).

How can we further improve these statistics and save more lives? By increasing awareness and education about heart attacks. It is a multifaceted approach: recognizing the symptoms and knowing what to do if you think you’re having a heart attack.

If you think someone is having a heart attack, call 911 as quickly as possible and have the patient chew an adult aspirin (325 mg) or four baby aspirin. In my May 15 article, I wrote that the Food and Drug Administration does not recommend aspirin for primary prevention of a heart attack. Please note that the use of aspirin in this case is for treatment of a potential heart attack, not prevention. It is also very important to know the risk factors and how to potentially modify them.

What are the symptoms of a heart attack? The main symptom is chest pain, which most people don’t have trouble recognizing. However, there are a number of other, more subtle, symptoms such as discomfort or pain in the jaw, neck, back, arms and epigastric, or upper abdominal, area; as well as nausea, shortness of breath, sweating, lightheadedness and tachycardia (racing heart rate). One problem is that less than one-third of people know these other major symptoms (2). About 10 percent of patients present with atypical symptoms — without chest pain according to one study (3).

It is not only difficult for the patient, but also for the medical community, especially the emergency room, to determine who is having a heart attack. Fortunately, approximately 80 to 85 percent of chest pain sufferers are not having a heart attack, but more likely having indigestion, reflux or other nonlife-threatening ailments.

There has been a raging debate about whether men and women have different symptoms when it comes to heart attacks. Several studies speak to this topic.

Let’s look at the evidence.

There is data showing that, although men have heart attacks more commonly, women are more likely to die from a heart attack (4). In a Swedish prospective (forward-looking) study, after having a heart attack, a significantly greater number of women died in-hospital or near term compared to men. The women received reperfusion therapy, artery opening treatment that consisted of medications or invasive procedures, less often than the men.

However, recurrent heart attacks occurred at the same rate, regardless of sex. Both men and women had similar findings on an electrocardiogram; they both had what we call ST elevations. This was a study involving approximately 54,000 heart attack patients, with one-third of them being women.

One theory about why women are treated less aggressively when first presenting in the ER is that they have different and more subtle symptoms, even chest pain symptoms may be different. Women’s symptoms may include pain in the lower portion of the chest or upper portion of the abdomen and maybe significantly less severe pain that could radiate or spread to the arms. But, is this true? Not according to several recent studies.

In one observational study, results showed that, though there were some subtle differences in chest pain, on the whole, when men and women presented with this main symptom, it was of a similar nature (5). There were 34 chest pain characteristic questions used to determine if a difference existed. These included location, quality or type of pain and duration. Of these, there was some small amount of divergence: the duration was shorter for a man (2 to 30 minutes), and pain subsided more for men than for women. The study included approximately 2,500 patients, all of whom had chest pain. The authors concluded that determination of heart attacks with chest pain symptoms should not factor in the sex of patients.

This trial involved an older population; patients were a median age of 70 for women and 59 for men, with more men having had a prior heart attack. This was a conspicuous weakness of an otherwise mostly solid study, since age and previous heart attack history are important factors.

Therefore, I thought it apt to present another observational study with a younger population, where there was no significant difference in age; the median age of both men and women was 49. In this GENESIS-PRAXY study, results show that chest pain remained the most prevalent presenting symptom in both men and women (6). However, of the patients who presented without distinct chest pain and with less-specific EKG findings (non-ST elevations), significantly more were women than men. Those who did not have chest pain symptoms may have had some of the following symptoms: back discomfort, weakness, discomfort or pain in the throat, neck, right arm and/or shoulder, flushing, nausea, vomiting and headache.

If the patients did not have chest pain, regardless of sex, the symptoms were, unfortunately, diffuse and nonspecific. The researchers were looking at acute coronary syndrome, which encompasses heart attacks. In this case, independent risk factors for nonchest pain-related disease included both tachycardia (rapid heart rate) and being female. The authors concluded that there need to be better ways to calibrate nonchest pain symptoms.

Some studies imply that as much as 35 percent of patients do not present with chest pain as their primary complaint (7).

So what have we learned about heart attack symptoms? The simplest lessons are that most patients have chest pain, and that both men and women have similar types of chest pain. However, this is where the simplicity stops and the complexity begins. The percentage of patients who present without chest pain seems to vary significantly depending on the study — ranging from less than 10 percent to 35 percent. Therefore, it is even hard to quantify the number of non
chest pain heart attacks. This is why it is even more important to be aware of the symptoms. Nonchest pain heart attacks have a bevy of diffuse symptoms, including obscure pain, nausea, shortness of breath and lightheadedness. This is seen in both men and women, although it occurs more often in women. When it comes to heart attacks, suspicion should be based on the same symptoms for both sexes. Therefore, know the symptoms, for it may be your life or a loved one that depends on it.

In my next article on June 5, we will discuss the risk factors associated with heart attacks, prevention and potential lifestyle modifications for the treatment of heart attacks, and the traditional medical regimen.

References:

(1) Circulation. 2014;128. (2) MMWR. 2008;57:175–179. (3) Chest. 2004;126:461-469. (4) Int J Cardiol. 2013;168:1041-1047. (5) JAMA Intern Med. 2014 Feb. 1;174:241-249. (6) JAMA Intern Med. 2013;173:1863-1871. (7) JAMA. 2012;307:813-822.

• If you would like to see a specific topic covered in Medical Compass, please email info@medicalcompassmd.com.

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 medicalcompassmd.com and/or consult your personal physician.

Harbormaster Peter Koutrakos observes the water from his patrol boat. File photo by Elana Glowatz

The Port Jefferson Harbor Complex is just that — a complex cluster of waterways that needs diligent eyes watching over it.

Those eyes belong to Brookhaven Town Harbormaster Peter Koutrakos and the others in his department, who are all working to keep the water safe this boating season.

The harbor complex includes Port Jefferson Harbor at its center, where Koutrakos is based, as well as Setauket Harbor and the adjacent Little Bay; Pirate’s Cove; Conscience Bay and the Narrows that lead into it; and a small section of water immediately outside Port Jefferson Harbor on the Long Island Sound that is bookended by Old Field Point to the west and Belle Terre’s Mount Misery to the east. Between these sections, the complex has more than 2,000 acres of surface water, and that area sees thousands of boats every season.

Peter O’Leary, the town’s commissioner of public safety, said between moorings and slips in the area, there are more than 1,200 spaces for boats, and that doesn’t include the ones just passing through.

On any given summer weekend, “the place is bedlam,” O’Leary said. “It creates quite a bit of traffic.”

With heavy traffic comes risk.

For Koutrakos, who has been harbormaster for 14 years and has jurisdiction in all town waters, it was the attack on the USS Cole in 2000 — an al-Qaida suicide attack in Yemen in which a small vessel next to the U.S. Navy ship was blown up, killing 17 Americans — that made him realize boats could be used as weapons.

Things also changed after the 9/11 terrorist attack. Officials became aware of the harbor’s vulnerability, as possible targets for terrorists include power plants, oil terminals and ferries — and Port Jefferson Harbor has all of them. Long Island has also been a concern in national security discussions because it is close to New York City and at the same time is remote: Ferries would be the only way off the island if an emergency event were to shut down transportation into the city.

The view of Port Jefferson Harbor from the harbormaster's patrol boat. File photo by Elana Glowatz
The view of Port Jefferson Harbor from the harbormaster’s patrol boat. File photo by Elana Glowatz

To keep the complex safe, the harbormaster works on a number of security exercises. One program, Operation Shield, involves coordinating with other agencies to randomly check foreign vessels for travel documents.

Though Operation Shield only runs on certain days, Koutrakos said he regularly does checks on his own. If the vessels do not have the proper documentation, he calls in customs officers to board and search them.

Another exercise he occasionally works on is search and rescue training with the U.S. Coast Guard, which helps prepare for an emergency situation, for instance if the ferry were to sink due to a mechanical problem or a bomb.

Koutrakos explained that the exercise group determines how to respond to an incident and who would take command of the scene. In the case of the ferry, officers also talk to the captain to learn how he would respond under certain circumstances and discuss a strategy for saving as many lives as possible, “before something really happens.”

The harbormaster also meets every few months with a Long Island security committee whose members range from the local to the federal level.

To boost security all over, O’Leary said, the town is working to install security cameras on its properties, and Port Jefferson is slated to receive some of that surveillance.

However, one of O’Leary’s concerns in protecting town waters is linked to the economy. He said budget cuts have meant cutbacks on seasonal employees, so there are fewer bay constables on both shores and they are working a shorter season. There are also fewer workers to pump out waste from the boats so it is not discharged into the water.

On Koutrakos’ end, he has an assistant harbormaster year-round and two seasonal harbormasters during the summer.

Most summer days, Koutrakos spends his time patrolling the waters and helping people who call him for assistance.

‘The place is bedlam. … It creates quite a bit of traffic.’
— Peter O’Leary

Born and raised in Port Jefferson, Koutrakos has a name people might recognize — his family owned the Elk Hotel and Restaurant on Main Street before it went out of business. He wife, Carol, works for the Port Jefferson ferry.

He has been around long enough to see security at the harbor change over the years. Before 9/11, if someone were to leave a bag at the ferry terminal, an employee would grab it and ask if anyone had left it behind. Now there are security protocols in place to handle such a situation. Before, there weren’t any restrictions on taking photos or video of the harbor. Now officials keep an eye out for people capturing the ferry terminal or other sensitive areas.

One thing that hasn’t changed is Koutrakos’ “only gripe with the job” — he isn’t permitted to carry a sidearm while he is on duty, though he is licensed to carry.

Other marine law enforcement agents carry a sidearm, including those from the Coast Guard, the Suffolk County Police Department’s Marine Bureau and the state Department of Environmental Conservation.

The harbormaster said he never knows what situation he will find himself in and “should we get put into a lethal force situation, the fact of the matter is we have no way of defending ourselves or the public.”

Despite this sticking point, another thing that hasn’t changed is Koutrakos’ playful personality and his passion for all things marine.

He has said he enjoys his job because he gets to be on the water and he gets to help people: “At the end of the day, tired or not, it makes you feel better.”

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It starts with a question and a possible explanation. From there, the leader tests to see whether he or she was right. If the initial information suggests the original possibility was accurate, the leader runs several other tests to confirm the result.

Scientists and researchers follow that formula to crack nature’s code. They tend to get excited when, for example, they find a certain gene appears to be involved in a particular disease. Researchers can be as disappointed as little league ballplayers after losing a close game if they find no such connection.

Jesse Gillis, an assistant professor of computational genomics at Cold Spring Harbor Laboratory, however, thinks many of those so-called negative results can be as constructive as finding positive ones. “Negative results are so valuable,” he said. Negative results help scientists understand all the available information and not just the usual suspects, especially in genetic disorders.

Often, tests for the role of key genes in diseases come up with some candidates almost every time, like P53, he said. P53 is a tumor suppressor gene, which means that, when it functions correctly, it prevents cells from developing into potentially deadly tumors. When other genes have some connection to a disease, they are often related to a gene like P53.

The interpretation of results is dominated by genes for which scientists already have considerable amounts of information. The interpretation of what is going on with numerous genes tends to be dominated by several important genes.

Gillis works in a field of computational biology in which researchers are looking for combinations of genes, RNA, and proteins that all could play a role in a disease. He studies a scientific field called “guilt by association,” in which combinations of mutations, signals, or defects might increase the likelihood of developing a complicated disorder, in which people with similar symptoms have a range of genetic differences.

He uses guilt by association to understand the combination of mutations which might increase the likelihood of developing a disorder like schizophrenia or autism.

Gillis hopes to be able to look closely into what these genes have in common to “be able to say when we have false positives.” In his opinion, attempts to give comprehensive lists of the genes causing complex disorders could produce false positives that could be as high as 50 percent. He says there is something of a specificity problem, where the overlaps among genes that might have a connection to schizophrenia are not specific enough.

Before he came to CSHL, Gillis conducted post-doctoral research in the laboratory of Paul Pavlidis, an associate professor at the University of British Columbia. Gillis impressed his former lab director. Gillis is “super-smart, serious and [a] skeptical scientist who is not afraid to question deep assumptions in our field,” Pavlidis offered.

Gillis said the notion of guilt by association is an older idea. Scaling that up to apply it to expressing a disease goes back to around the turn of the millennium, when scientists started applying computational principals to these data ranges.

Where Gillis hopes to make a difference is finding something meaningful to say based on the data, instead of echoing other findings.

Gillis, who grew up in Toronto, said he “always liked messy data.” He was not as excited by the typical experiment where scientists tested one hypothesis and the results either worked or they didn’t. He enjoyed studying data-driven discovery, where he could look at a combination of data that was diverse and potentially challenging to understand and interpret.

Gillis’s scientific curiosity is, in part, a product of his childhood environment. His father is a math professor, while his mother started her doctorate in developmental psychology by watching him play as a child.

Most of his American experiences have been on Long Island. He has been so busy setting up his lab — he arrived a year and a half ago — that he hasn’t had many opportunities to pursue his penchant for sailing.

Gillis hopes to have more data to work with in the coming years. “If I say genes are likely to have a property x or this set of genes is likely to have a property x, it matters how prevalent that property is,” he said. “If a gene is always important” then finding it has a role in a disease doesn’t “validate the reason it’s important in this context.”

The negative result might tell scientists more because “the gene not showing up is the more unusual finding.”

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Primary prevention of cardiovascular disease called into question

Aspirin has been around for thousands of years — known as a salicylate — but the form we are most accustomed to was discovered by a scientist named Felix Hoffmann, who worked for Bayer, in 1897 (1). Presently, there are over 100 billion tablets of aspirin consumed worldwide on annual basis (2). It is one of the most broadly accepted prophylactic medications. It has been used for a long time in primary prevention — those who are taking the medication to prevent the disease but don’t have it. Thus, you would think that we know all about aspirin, including its effectiveness as a prophylactic in different diseases and its side effects. However, this is far from reality.

In modern day, aspirin is used mainly for its antiplatelet effects, preventing clots and as an anti-inflammatory rather than for its antipyretic (fever) and analgesic (pain) benefits.

Is it beneficial, or is it oversold and dangerous? Every time we think we know the answer, another new study says the opposite. In other words, for every positive study, there are also negative studies about its side effects and complications.

Aspirin may play a role in a number of diseases, including cardiovascular disease (stroke and heart disease); multiple cancers, such as colorectal cancer and liver cancer; and age-related macular degeneration.

However, there are several risks with aspirin. The two most widely known side effects are gastrointestinal bleed and intracranial hemorrhage, or bleeding in the brain. Let’s look at the evidence.

Cardiovascular disease

Aspirin’s prophylactic role may be in question. We’re certain that aspirin works in primary prevention of cardiovascular disease, right? Why else would we put so many people, who were otherwise healthy, on aspirin? Not so fast. The Food and Drug Administration and recent studies indicate that aspirin may not be effective, or the evidence is inconclusive when comes to benefit outweighing risk.

Bayer AG, the pharmaceutical company, requested a change in the low-dose (baby aspirin or 81 mg.) aspirin label to include prevention of heart attacks. The company wanted to market the drug for those who were otherwise healthy but wanted to prevent a heart attack. The FDA, spurred by this requested change, stated on May 5 that the evidence for using aspirin in primary prevention of cardiovascular disease, including both heart attack and stroke, was not convincing or supportive enough to recommend the drug for this use (3). The FDA also said that the patients who wanted to use it for this indication should talk to their doctor about the risk-benefit ratio.

This response came as a surprise to many in the medical community considering that the American Heart Association, contrary to the FDA, supports aspirin use in in those who are at high risk for cardiovascular disease development. However, the agency did say that those who already have cardiovascular disease should be taking aspirin. But this is secondary prevention that the FDA supports, not primary. If you are already on aspirin for primary prevention, you should discuss it with your doctor before stopping the medication.

This is still a highly controversial issue, but it does not help that the FDA, one of the most respected institutions in medicine, weighed in on the topic to suggest that the risks may outweigh the benefits.

According to a study published in Lancet, the side effects may outweigh the benefits, as the FDA implied (4). Aspirin may also detract from the effectiveness of some cardiovascular risk-reducing classes of blood pressure lowering medications, such as angiotensin-converting enzymes inhibitors, like Lisinopril (5). Another study shows that aspirin is also associated with hearing loss (6).

There is also a suggestion that aspirin may increase the risk of macular degeneration. Let’s investigate this further.

Age-related macular degeneration

A recent observational study suggests that aspirin increases the risk of one type of advanced-stage macular degeneration by almost 2.5-fold in those who used aspirin on a chronic (weekly or more) basis (7). This type of macular degeneration is referred to as wet, or neovascular, AMD. However, there was not an increased risk in a second form of advanced AMD, geographic atrophy. This study followed 2,389 patients for 15 years.

Therefore, we should not use aspirin if patients have a high risk for AMD or have early stage AMD, right? Not necessarily. This study was flawed and difficult to apply to this country; it was done in Australia, and the dose most commonly used was assumed to be 150 mg., but the doses were not quantified. Aspirin does not come in this dose in this country. Also, patients were asked only at the start of the trial how frequently they used aspirin over the last year. Therefore, there was also recall bias.

In another study, aspirin did not show an association with an increased risk of AMD (8). I said it was complicated.

Colorectal cancer

We have thought that aspirin may prevent the occurrence of colorectal cancer. There are some studies suggesting this is the case and others suggesting no effect. But there is a new wrinkle in this discussion. A recent study implies that your DNA may be an important factor to determining whether you will see a benefit from aspirin as a preventive of this cancer (9).

If your genes produce a large amount of an enzyme, 15-PGDH, then there is a significant 50 percent reduction in the risk of developing colorectal cancer in those whose use low-dose aspirin regularly, while those who produce low levels of the enzyme only see a 10 percent reduction in colorectal cancer with aspirin.

The reason is that aspirin and the enzyme both help control prostaglandins, which can be inflammatory. Together, the combination seems to have a profound effect on risk reduction. About half of the population produces significant amounts of the enzyme. You can test for this enzyme through colon biopsy during a routine colonoscopy. Therefore, targeted aspirin use may be the answer in colorectal cancer prevention.

Aspirin is obviously a tricky topic. At best, it prevents one in five cardiovascular events — stroke and heart attacks. This number comes from those who already have cardiovascular disease, and this may not be the case for primary prevention. Because aspirin has significant side effects, it is best not to depend on it for prevention in “healthy” individuals until there is solid data that it is an effective agent. However, it may make sense to prevent colorectal cancer in those who have complementary DNA, but we need larger, well-controlled trials confirm these results. As always, consult with your doctor before starting or stopping an aspirin regimen.

References:

(1) Tex Heart Inst J. 2007;34:179-186. (2) Proc Natl Acad Sci USA. 2002;99:13371-13373. (3) fda.gov. (4) Lancet. 2009;374:878. (5) J Am Coll Cardiol. 2001;38:1950-1956. (6) Am J Med. 2010;123:231-237. (7) JAMA Intern Med. 2013;173:258-264. (8) PLoS ONE. 2013;8:e58821. (9) Sci Transl Med. 2014;6:233re2.

• If you would like to see a specific topic covered in Medical Compass, please email info@medicalcompassmd.com.

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 medicalcompassmd.com and/or consult your personal physician.

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By Linda M. Toga, Esq.

The Facts: I bought my boyhood home from my parents when they moved into a 55 and over community. The house was built by my parents in the 1980’s. Despite the fact that the driveway is in the same location now as it was when the house was first built, my neighbor brought over a new survey that suggests that my driveway crosses over his property. He is demanding that I sign a document that states that I do not claim to own the land over which my driveway passes.

The Question: What should I do?

The Answer: What you should do will depend on a number of factors but, the one thing you should not do without consulting an attorney is to sign the document he presented to you. Who actually owns the disputed strip of land and who has the right to use that land will depend on the circumstances surrounding the construction of the driveway in its current location and how the disputed property has been used since the driveway was constructed.

If the driveway was initially positioned on the disputed strip of land based upon your parents’ belief that the land was actually part of their property, and if your family’s use of the land has been continuous since the driveway was constructed, you may have a valid ownership interest in the disputed strip of land. You can commence an adverse possession action in state court and ask a judge to make a determination as to whether the facts support your claim that the land over which your driveway passes is, in fact, yours. If you the judge rules in your favor in the action, you will be declared the rightful owner of the property.

However, even if you do not prevail in the adverse possession action, a court may decide that the long time use by your family of the disputed land justifies the creation of an easement in your favor. In that case, you would not be deemed the owner of the disputed land but, you would have the right to use the driveway in its current location and your neighbor would not be allowed to interfere with that use. Since the easement would run with both your property and your neighbor’s property, the rights and obligations inherent in an easement would apply to all future owners.

Linda M. Toga, Esq. provides legal services in the areas of litigation, estate planning and real estate from her East Setauket office.

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Their world stretches from the treetops of Madagascar to the rain forests of Brazil to the salmon feeding grounds of bears in Alaska.

They study a wide range of animals, at the same time that they dedicate their work to the survival of species with uncertain futures.

Russell Mittermeier, Carl Safina, and Patricia Wright not only share a connection to Stony Brook University and to conservation, but they are also three of six finalists for the biennial Indianapolis Prize, considered the top award for the world’s conservationists. The award, which is administered by the Indianapolis Zoo, considers conservation candidates from all over the world. The winner, who will receive the Eli Lilly Medal and a $250,000 prize, will be announced on May 13.

“I am very proud of these outstanding members of our faculty,” SBU President Stanley said through an emailed statement to the Times Beacon Record Newspapers.

The three finalists recently attended an Earth Day tweet-up at the Student Activity Center at Stony Brook, where they shared their views on the prize, on conservation, and on the Long Island ecosystem. It was the first-ever Tweet-Up for the University. Members of the school, including Stanley and representatives from the Indianapolis Zoo, attended the discussion.

“Having three of the six finalists from Stony Brook speaks to the institution’s tradition of academic excellence and commitment to field work that positively impacts genuine conservation,” Rob Shumaker, the vice president of Conservation & Life Sciences at the Indianapolis Zoo, said after the meeting.

On the positive side, the tweeting trio talked of a comeback for a bird of national symbolic importance that hasn’t nested on Long Island since Dwight Eisenhower was president.

“Here on Long Island, for the first time in 60 years, we have a nesting pair of bald eagles,” said Safina. The head of the Blue Ocean Institute, Safina has written six books on threats facing the world’s habitats.

One of the strongest pieces of advice each of the Stony Brook finalists offered is to see animals in their natural habitat.

“Once you get out there, you’re connected for life,” Mittermeier, a leading field biologist who is also the president of Conservation International, told a combination of about 200 people in attendance at the SAC and those gathered in a virtual crowd through Twitter.

“Visiting places is not a trivial part of the fight for wildlife conservation,” Safina echoed.

Indeed, in 2012, Stony Brook inaugurated a new research, education and conservation building on the boundary of Ranomafana National Park in Madagascar called NamanaBe Hall. Stanley attended the inauguration, along with dignitaries from Madagascar.

The university president agreed that the experience of seeing these animals in the wild brings a new perspective.

“Observing [creatures] in their natural habitat brings a completely new level of awareness and appreciation for them and it is an extraordinary experience,” Stanley said.

Wright, who has studied lemurs for over a quarter of a century, was recently featured in an Imax movie narrated by Morgan Freeman called “Island of Lemurs: Madagascar.” The film, which Wright has seen 16 times and includes footage of lemurs on that island, shows the interactions of lemur social groups. Back in her office after the tweet up, Wright shared a chart that tracks how one female lemur leader lost her role in a “hostile takeover,” only to assume the same position with another group.

Wright, who helped establish Ranomafana National Park in 1991, calls the lemurs “her family,” along with her daughter and her well-traveled graduate students who have been to Madagascar and Peru.

Mittermeier, meanwhile, discussed how conservation groups are looking to turn the 2016 Olympic spotlight for host city Rio de Janeiro on some of Brazil’s conservation efforts.

Conservation International is joining other groups to suggest that the mascot could either be the muriqui or the golden lion tamarin. The muriqui, which weighs between 10 and 20 pounds, is an endangered monkey that is found only in the Atlantic coast forests of Brazil. Mittermeier also is urging the Olympics to use the tamarin, a monkey with reddish brown hair around its head and face that is considered a conservation success story, as an image on gold medals.

While he won’t likely be making an appearance in Brazil, Stony Brook’s own mascot Wolfie prowled around the ballroom during the Earth Day Tweet-Up.

Stony Brook officials said they were pleased with their first-ever tweet up and are interested in hosting this type of event again. The talented trio said it would be an honor to win the prize and that it underscores the appreciation for the value of their work.

As for why conservation is important, Safina explained, “it’s about trying to be human without ruining the world.”

Wright said she felt she “couldn’t be a person if she let all these animals go extinct.”

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Women may not see the same benefit as men

High cholesterol affects a great deal of Americans – millions upon millions (a modified homage to the late, great scientist Carl Sagan), and cuts across many demographics, affecting young and old and those in between.  When we think of hyperlipidemia (high cholesterol), what do you think is the mainstay of medical treatment?  If you said, “statins,” you would be correct. 

Do statins deserve this central role in treatment?  They have been convincingly shown in studies to significantly lower cholesterol, and they play an important role for those who have cardiovascular disease.  However, should we be using statins as liberally as we have?  Well, the new guidelines for the treatment of high cholesterol, which came out in Nov. 2013, suggest that we should.  In fact, these guidelines would most likely increase the use of this medication, especially in those over the age of 60.  Some in the medical community have even joked that statins might as well be put in the drinking water.  To read more about the guidelines, please see my November 20, 2013 article, entitled “New cholesterol guidelines released,” online at northshoreoflongisland.com.

This is a medication that patients may be on for life.  I don’t know about you, but that thought sends chills down my spine.  We know all medications have pros and cons.  Statins are no exception; they have been mired in controversy.

For one thing, they have side effects.  These include possibly increasing the risk of diabetes, myalgias (muscle pain), hepatic (liver) toxicity, kidney disorders and negatively affecting memory.

They also may reduce the benefits of exercise, and they may not be as effective in women as they are in men.

Because statins are such effective cholesterol-lowering medications, does this mean that patients on these drugs may become complacent with their diets?   A new study indicates that this is exactly what might be happening.

Let’s look at the evidence.

Diet complacency

The “S” in statins does not stand for “super immune to eating anything.”  In a newly published study in JAMA Internal Medicine, results show that those who are taking statins tend to eat more calories and fats and, ultimately, increase their (body mass index) by gaining weight, compared to those who were not taking statins. (1)  In fact, in this study that used 11 years of NHANES data, results showed that there were a 14 percent increase in fat intake and an almost 10 percen increase in overall calorie intake among statin users.  This resulted in a BMI that rose by 1.3 percent in those on statins, while in non-users over the same period, BMI only rose by 0.4 percent.

In other words, if you took an average male who was 5 feet 9 inches and weighed 200 lbs., the difference between statin users and non-users would be the difference between obesity and being just below obesity.  Those on statins were consuming about 200 extra calories a day.  This increase in calorie consumption occurred after they were placed on statins.   Their weight also increased by 6.6 to 11 lbs.  This is especially concerning to the researchers, since the guidelines for statin use call for a prudent diet to help reduce fat and calorie intake with the ultimate goal of reducing weight. 

However, the opposite was found to have happened – consuming more calories and gaining more weight. This is an observational study with over 27,000 participants, therefore no firm conclusions can be made.  However, statins are not a license to gorge at the all-you-can-eat buffet line.  We already know that statins may increase the risk of diabetes.  Why worsen this risk with dietary indiscretions that are harmful to your BMI?  As an aside, the authors note that this increased calorie and fat consumption may be a contributing reason for the increased risk of diabetes with statins, but it’s too early to tell.

Impact on women

We tend to clump data together from trials that focus predominantly on one demographic, in this case men, and apply the results broadly to both men and women.  However, in a May 5 article in the New York Times, some in the medical community, including the editor of JAMA, note that this may be a mistake. (2)  According to the dissenters, the thought process is that women have been underrepresented in statin trials, and cholesterol may not play the same role in women as it does in men.  Yet almost half of the patients treated with statins are women.  These physicians referring to the use of statins in primary prevention, or in those who have high cholesterol, but who do not have documented heart disease.

Lest you think their views are based solely on opinion or anecdotal data from clinical experience, this data on women was from the JUPITER trial, which looked at almost 7,000 initially healthy female participants. (3)  Statins did benefit women by reducing the occurrence of chest pain and reducing the number of stent placements and bypass surgeries, but they did not reach the primary endpoints of showing statistical significance in reducing the occurrence of a first heart attack, stroke or death.

The caveat is that there were not a large number of cardiovascular events – heart attacks, strokes or death – that occurred in either the treatment group or the control group. These results were in women over the age of 60.  This may give slight pause when giving statins.  By no means do I think these physicians are advocating to not give women statins, just that we may want to weigh the benefits and risks on a case-by-case basis.

Tamping down exercise benefits

Since exercise is beneficial for lowering cardiovascular disease risk and statins are as well, the logical presumption might be that the two together might create a synergistic effect that is greater than the two alone – or at least an added benefit from combining the two.  Unfortunately, what seems straightforward is not always the case.  In a small, yet randomized controlled trial, participants who were put on statins and monitored for cardiopulmonary exercise saw a blunted aerobic effect compared to the control group, which exercised without the medication. (4) In the treatment group, there was a marginal 1.5 percent improvement with aerobic exercise, while the control group experienced a much more robust 10 percent gain. The reason for this disappointing discrepancy is that statins seem to interrupt the enzymes that are responsible for making the mitochondria (the powerhouse or energy source for the cell) more efficient.  The most troubling aspect of this trial is that the participants chosen were out of shape, overweight individuals in need of aerobic exercise.

Whether or not a patient, male or female, is placed on cholesterol-lowering medication, one thing is clear: there is a strong need to make sure that lifestyle modifications are always emphasized to help reduce the risk of cardiovascular disease to its lowest levels.  But the quandary becomes what to do with statins and exercise.  And statins, as powerful and effective as they may be, still do have side effects, may reduce exercise benefits, and may not have the same effects for women.  Thus, they may not be appropriate for everyone.  A healthy diet and exercise, however, are appropriate for all.

References:

1 JAMA Intern Med. online April 24, 2014.  2 nytimes.com.   3 N Engl J Med. 2008 Nov 20;359(21):2195-207.  4 J Am Coll Cardiol. 2013;62(8):709-14.

* If you would like to see a specific topic covered in Medical Compass, please email info@medicalcompassmd.com.

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 medicalcompassmd.com and/or consult your personal physician.

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Ivan Iossifov is using computer programs to try to understand the genetic piece of the autism puzzle. An assistant professor at Cold Spring Harbor Laboratory, Iossifov is comparing the genome of people with autism with the sequences from their unaffected siblings.

Iossifov explores areas of the genome where mutations might increase the risk of autism. He is searching for a “list of genes that, when you take it, can lead to autism directly or can increase the risk of a child being autistic,” he said. “Some genes are frequently mutated in autism.”

He can approach this mission by looking at “every nucleotide in each parent and each sibling,” he said. “We can zoom in on very particular genes.”

Historically, he said, genetic technology first allowed scientists to look for large-scale copy-number events, where a sequence of DNA might be repeated more frequently for one group of people than for another. As genetic sequencing has matured, however, he has been able to focus on nucleotide-level genetic variants, such as single base-pair substitutions.

“The new-generation sequencing technology becomes cheaper and faster amazingly quickly,” he said. “That does allow us to perform research that was unfeasible even five years ago.”

Iossifov said the research he’s conducting may help doctors and scientists understand some of the genetic components of autism. So far, his research shows that early genetic-based diagnosis is difficult. He estimates that he needs about ten times more genetic data in families before genetic-based diagnoses can become useful. While he said he is not an expert in autism, he said he strongly believes “that the earlier a child can be reliably diagnosed, the better.”

More broadly, Iossifov is interested in a large scope of neurodevelopment disorders as well as cancer. In the last few years, however, he’s focused considerable effort and attention on autism.
Autism, he explained, seems to require the kind of approach he has to research, looking at the big picture and narrowing that down to individual genes or even base pairs. So far, he has looked at the 1 percent of the nucleotides in the human genome that encode genes.

“We have been carefully examining each variant for its potential effect on the gene it belongs to,” he said. “We analyze thousands of families, focusing in on de novo variants,” variants present in a child and not in her parents.

Iossifov is now planning to extend his analysis over the complete genome. He is hoping to hire new staff before long, to help with data collection and analysis.

Iossifov is grateful for the backing of the Simons Foundation, which provided funding and supported the collection of many of the genetic samples he is studying. He hopes the foundation will continue to endorse efforts to scrutinize additional areas of the genome, even those that other scientists hadn’t previously considered, to find other regions where he might discover “interesting variants.”

Iossifov splits his time between Philadelphia, where his wife Ani Nenkova works in the Department of Computer and Information Science at the University of Pennsylvania, and Long Island. The couple have a four-year old son Pascal, whom they call “Paco.”
When he’s on Long Island, he enjoys visiting beaches. Iossifov said he speaks “one and a half” languages, although, at this point, he’s not sure which is the half. He grew up speaking Bulgarian, but his friends at home suggest he’s developed an American accent in his native tongue. “I apparently sound funny” speaking Bulgarian, he said.

Iossifov said his parents didn’t push him to do anything in particular, although he is following somewhat in the footsteps of his father, who is a retired chemist.

In terms of teaching their son about the world, Iossifov and Nenkova encourage him to understand that “he can go deeper,” in whatever he learns.

Iossifov is excited to continue working with autism. “Autism is a complex disorder and is highly prevalent. Any progress on autism would be great on many aspects.”

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