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Monthly Archives: October 2014

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Fruits and vegetables significantly decrease risk

Last week, I wrote about factors that increase the risk of gallstones, an all-too-common GI problem. Many of these are modifiable. A logical extension of this discussion is complications and prevention techniques. Let’s look at the evidence.

What are the complications?

Complications include cardiovascular disease, psoriasis and pancreatitis. I wrote about how gallstones are the major risk factor for acute pancreatitis in my Oct. 16, 2014 article, entitled “How much do you know about pancreatitis?” Here, we will touch on some of these additional complications.

Cardiovascular complications

Cardiovascular disease, comprised of heart disease and stroke, is responsible for about 45 percent of deaths in the United States. In a recent observational, prospective (forward-looking) study, the results show an overall 32 percent increased risk of cardiovascular disease in patients with gallstones (1). When these results are further broken out, there was a 42 percent increased risk of heart disease, 15 percent increased risk of stroke, and a 31 percent increased risk of heart failure. These results are scary, and it is not even Halloween yet.

Interestingly, those who were younger, 18 to 40 years old, were at the highest risk of developing cardiovascular disease. And those who had mild gallstone disease were at higher risk, as well. This study was six years in duration and involved more than 34,000 patients. The authors hypothesized that the possible reason for this association, between gallstones and cardiovascular disease, may have to do with an abundance of cholesterol, inflammation and oxidative stress.

Psoriasis & Psoriatic Arthritis

In the Nurses’ Health Study II, a prospective observational trial, results show that there is a 70 percent increased risk of developing psoriasis and an 196 percent increased risk of developing psoriatic arthritis in women who have a personal history of gallstone disease (2). These results were segregated from obesity. In fact, this association between gallstones and psoriasis was greatest in those who were <30 BMI — a threefold increased risk.

This is not an excuse to be obese, however, because there was still a significantly increased risk, 1.71-fold, in this group. There were 89,234 women involved in this study over a 14-year follow-up period. As with cardiovascular disease’s association with gallstones, inflammation also may play a role with gallstones and psoriasis and psoriatic arthritis. Therefore, it may be important to reduce inflammation in the body to prevent gallstones and their complications.

prevention 

Fortunately, there are several ways to reduce the occurrence of gallstones, including lifestyle changes with exercise and diet, such as coffee, more fiber, statins and unsaturated non-trans fats (3).

physical activity

In last week’s article on risk factors for gallstones, low physical activity increased the risk of this disease. It turns out that the opposite is also true. In the Physicians’ Health Study, results showed a significant reduction in the risk of gallstones in those in the highest quintile of activity compared to those in the lowest quintile (4). In fact, men who were in the highest quintile and under 64 years old saw the greatest reduction — 42 percent — in the risk of gallstones. However, those over the age of 65 and in the highest quintile of activity also had substantial reductions in risk — 25 percent. There were 45,813 men involved in this study over an eight-year duration. The authors concluded that, overall, 34 percent of symptomatic gallstones could be avoided if men did aerobic training for an average of 30 minutes per day, five days a week.

Fruits and vegetables

If you ever needed another reason to consume more fruits and vegetables, reducing the risk of gallstones may motivate you.

In the Nurses’ Health Study, the results showed that those in the highest quintile of fruit and vegetable intake had a 21 percent reduction in the need for a cholecystectomy (surgery to remove the gallbladder, usually due to symptomatic gallstones) compared to those in the lowest quintile (5). Interestingly, fruits and vegetables looked at separately had the same significant reduction as fruits and vegetables taken together. There were 77,090 women involved in the study with a duration of 16 years.

The fruits and vegetables consumed in the study were common; they included citrus fruits, green leafy vegetables, cruciferous vegetables, and other vitamin C-rich fruits and vegetables. The authors surmise that the effect may be due to antioxidants, vitamin C, dietary fiber, and minerals like magnesium – and to the interactions among these different components.

This was not just a reduction in gallstones, but a reduction in the actual number of surgical procedures. This makes it a very powerful study. To give perspective, there are around 800,000 cholecystectomies done each year in the U.S. (6).

rapid weight-loss diets

I mentioned in last week’s article that rapid weight loss increases the risk of gallstone formation. However, if you were going to attempt a rapid weight-loss diet, which is better: high-fiber or high-animal-protein? Well, in a small, randomized controlled study, the gold standard of studies, results show that a high-fiber, very low-calorie diet had one-third the number of patients with gallstone formation compared to a high-protein, very low-calorie diet (7).

Although it is better not to lose weight rapidly, as far as gallstones are concerned, there may be lower risk with a high-fiber diet rather than with an animal-protein-dominant diet. It is important to note that this study considered rapid weight loss to be more than 20 pounds. in a month. Both groups lost about the same amount of weight. However, the high-fiber diet resulted in less biliary sludge. The study included 68 patients with a mean BMI of 35 kg/m2, severely obese, at the start of the trial.

Coffee effect

Coffee must be one of the more controversial beverages. Using the Swedish Mammography Cohort and the Cohort of Swedish Men studies, a meta-analysis of two studies, the results show that only women, not men, had a significantly reduced risk of undergoing cholecystectomies in those who drank at least six cups of coffee a day, versus those who drank fewer than two cups (8). And this effect was not seen in all women, but only in those women who were premenopausal or on hormone replacement therapy. A cup was considered eight ounces. Does this mean these specific women should drink more coffee? Not necessarily, for it seems as if every good result is balanced out with a bad result when it comes to coffee and gallstones.

In conclusion, it is important to prevent gallstones, since this disorder can lead to significant complications, including cardiovascular disease and death. Lifestyle modifications and even some medications may reduce the risk of gallstones, which in turn could have a beneficial impact on reducing heart disease and strokes, as well as autoimmune diseases, such as psoriasis and psoriatic arthritis. Inflammation seems to be the common denominator when it comes to gallstones, their complications and the ways to prevent them.

References

(1) PLoS One. 2013 Oct 3;8(10):e76448. (2) Br J Dermatol. online Oct 11, 2014. (3) uptodate.com. (4) Ann Intern Med. 1998;128(6):417. (5) Am J Med. 2006;119(9):760. (6) AdvData. 2002;(329):1-19. (7) Georgian Med News. 2014;(231):95-9. (8) Clin Gastroenterol Hepatol. online Sep 19, 2014.

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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Seeing isn’t just believing — it can also lead to understanding. David Jackson of Cold Spring Harbor Laboratory has developed a way to see just what’s happening with important signals inside the cells of maize, a crop plant that is used in everything from cattle feed to corn syrup to oil, and even glue.

“We want to figure out what’s going on inside the cell: how they respond to treatment or processes,” said Jackson, a professor at Cold Spring Harbor.

Jackson and his collaborators use fluorescence to see proteins and hormones in action. They are not the first to use this technique in living cells, but they are the first to apply it to maize.

Labeling molecules can allow scientists to see where they go “during growth and development,” said Anne Sylvester, a professor in the Molecular Biology department at the University of Wyoming, who worked with Jackson to develop this technique. This allows researchers to see how a protein is regulated, what it’s doing and even suggest ideas on how to control it.

Jackson and Sylvester have made a large collection of these reporter lines and have sent them out to “hundreds of labs,” so other researchers can “use the tools we’ve generated,” Jackson added.

In his lab, Jackson is focused on how the plant establishes and maintains stem cells — which are like blank pieces of biological clay that genes and other molecules can mold into anything in a plant.

At the same time, Jackson and the six post doctoral students in his lab are working on several other projects. In collaboration with Doreen Ware’s lab at Cold Spring Harbor, Jackson has been taking huge amounts of data to explore how genes work together.

“We found connections between different genes we’ve been studying for a long time,” he said. “We didn’t suspect” that link before, but, “in hindsight, it makes perfect sense.”

In a paper published in March in Genome Research, Jackson, Ware, and Andrea Eveland, an assistant member of the Donald Danforth Plant Science Center, among others, showed that the transcription factor Ramosa1 and Knotted1, a regulator of stem cell maintenance, were teaming up to control branching. This, the authors explained in their paper, is an important factor in crop yield, affecting seed number and harvesting ability.

Jackson has “been making great strides in discovery of novel components of stem cell signaling, and translating these findings directly to crop improvement, which really is the ultimate goal of our research as plant scientists,” said Eveland, who worked as a post doctoral student in Jackson’s lab for more than five years.

In addition to analyzing data on genes, Jackson and his lab use Crispr, a tool that is the DNA equivalent of the game Jenga, which can knock out individual pieces, allowing them to see the effect on the plant.

“Many genes are redundant,” he said, so knocking one out doesn’t necessarily change anything because, like a car navigating along a detour, the plant can take an alternate genetic route to arrive at the same destination.

Jackson has won fans among his collaborators. Sarah Hake, the center director of the USDA Plant Gene Expression Center at the University of California at Berkeley, and Jackson’s post doctoral mentor, called him “a superstar.” He has “brilliant ideas” and is “well known in maize genetics and developmental biology.”

He also requires precision and accuracy among his fellow scientists.“When someone showed data at a lab meeting that was poorly done, he would politely call it rubbish,” Hake recalled. “He set a high standard that kept our lab at the top.”

At the same time, Jackson has been an “incredible teacher” and role model to scientists in training. He has contributed to Sylvester’s outreach programs in Montana to help teach genetics and cell biology at a tribal college for Native Americans.

While Jackson doesn’t do any lab bench-work anymore, he conducts field work at a Cold Spring Harbor Laboratory farm during the summer and in Puerto Vallarta in the winter.

Jackson and his wife Kiyomi Tanigawa, an interior designer, live in Brooklyn with their six year-old son, Toma.

Originally from the north of England, Jackson has been at Cold Spring Harbor for 17 years.

In his work, Jackson said he is thrilled with the advances in technology.

“There is a revolution in biology,” he said, adding that Crispr, and other tools, will “open up so many different areas we can address.”

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By Linda M. Toga, Esq,

At least once a week a new client who owns real property with someone else comes to my office with a question about his rights and obligations with respect to his joint ownership of the property. Oftentimes the questions arise because the owners do not see eye to eye as to who is responsible for paying the carrying costs on the property (real estate taxes, insurance, maintenance and repairs) or how the proceeds will be divided in the event the property is sold. Since joint ownership of property can take a number of forms, each conferring different rights and obligations upon the owners, the answers to these questions require an understanding of the different ways in which people can jointly own property.

Individuals who are not married to each other can own real property as tenants-in-common or as joint tenants with right of survivorship. In addition, spouses can own real property as tenants-in-the-entirety.

Owners who are tenants-in-common each own a share of the real property. They have the right to sell or transfer their own share to whoever they want without the consent of the other owners, either during their lifetime or by Will. Tenants-in-common need not own equal interests in the property. For example, if three people own a piece of property as tenants-in-common, each may have a one-third interest in the property but, one may have a one-half interest while the others each have a one-quarter interest. Since the ownership interests may not be the same for each tenant-in-common, it is important that the percentage of the property owned by each tenant-in-common is set forth on the deed. It is also important that tenants-in-common set forth in writing what their obligations are with respect to the carrying costs associated with the property. Generally each owner’s share of the carrying costs is the same as his ownership interest in the property. For example, if four people each own 25% of a property, they are each responsible for paying 25% of the carrying costs. However, the owners may agree to a different arrangements, especially if not all of the owners reside or make use of the property. To avoid confusion and disputes, a detailed agreement setting forth the rights and obligations for each tenant-in-common should be signed by all of the owners. In addition, detailed records should be kept of contributions made by each owner toward the cost of owning the property.

Unlike tenants-in-common, when more than one person owns property as joint tenants with right of survivorship, it is assumed that each owner has an equal ownership interest in the property. Joint tenants are not free to sell or otherwise transfer their interest in the property to a third party without consent of the other joint tenant owners. In addition, a joint tenant with right of survivorship cannot leave her share of the property to someone in a Will. That is because the right of survivorship essentially guarantees that the “last person standing” is the sole owner of the entire property. For example, if there are three joint tenants and one dies, the two remaining joint tenants automatically become the sole owners of the entire property. Upon the death of one of the remaining joint tenants, the survivor becomes the sole owner of the entire property. This is true even if the other joint tenants died with Wills explicitly leaving their interests in the property to a third party. Like tenants-in-common, joint tenants should set forth in writing what their obligations are with respect to the carrying costs of the property and how the proceeds from the sale of the property will be divided if not equally.

Although anyone can own property as tenants-in-common or joint tenants, only spouses, both traditional and same sex, can own property as tenants-by-the-entirety. In fact, in New York, even if the deed does not specifically indicate that ownership is by tenants-in-the-entirety, real property is assumed to be held by spouses as tenants-in-the-entirety absent language in the deed to the contrary. Even if a deed simply provides that the owners are “John Doe and Jane Doe, his wife,” it is presumed that John and Jane are tenants-in-the-entirety. If they wish to hold the property as tenants-in-common, the deed must specify that they are tenants-in-common and must indicate the size of each owner’s interest in the property. The rights and responsibilities associated with tenants-in-the-entirety are identical to those associated the joint tenancy with the right of survivorship. Like joint tenants with right of survivorship, tenants-by-the-entirety cannot dispose of their share as they please. Rather, upon the death of the first spouse, the surviving spouse automatically owns the entire property. A divorce will sever a tenancy by the entirety, resulting in the owners being tenants-in-common.

Because of complexities associated with jointly held property and the potential for unintended consequences, it is good idea to consult an attorney when purchasing property with others to insure that you understand your rights and obligations and have taken the steps necessary to protect your interests.

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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School building has lasted through ups and downs in Port Jefferson Village

Port Jefferson’s old high school on Spring Street, above, was made of wood and burned down on July 4, 1913. Photo from the Port Jefferson Village Digital Archive

A lot has changed in the last century, but Port Jefferson’s Spring Street school building still stands.

BOCES social worker Christian Scott, special education teacher Patricia Dolan and Principal Chris Williams wear period clothing to celebrate the Spring Street school building's 100th birthday. Photo from BOCES
BOCES social worker Christian Scott, special education teacher Patricia Dolan and Principal Chris Williams wear period clothing to celebrate the Spring Street school building’s 100th birthday. Photo from BOCES

Eastern Suffolk BOCES, which leases the school building from the Port Jefferson school district, recently celebrated the building’s 100th birthday, with festivities that included period costumes and popular music from the era — the 1914 hit “By the Beautiful Sea” and a World War I marching song from 1915, “Pack Up Your Troubles in Your Old Kit Bag.” There was also a ribbon-cutting ceremony and lots of cake at the school at Spring and High streets, which is now officially called the Jefferson Academic Center.

Though the mood was light that day, the road leading up to the 100th birthday bash was a rocky one.

Another building, the original Port Jefferson High School, once stood in that same place, but it burned down on Independence Day in 1913.

According to the village’s historical archive, it is still a mystery what caused the fire, which started the night before. At the time, many believed that some young people broke into the building so they could ring the bell at midnight to celebrate July 4. They believed the kids started the fire by accident while using matches to light their way in the dark building.

The Spring Street school building went up in 1914. Photo by Barbara Donlon
The Spring Street school building went up in 1914. Photo by Barbara Donlon

There was also a theory that an arsonist lit up the wooden building, according to the archive. A suspect was presented to a Suffolk County grand jury, but he was not indicted.

The current Spring Street building was erected the following year, with the community laying its cornerstone on May 2.

According to Eastern Suffolk BOCES, $75,000 went toward the new brick and stone structure, which had separate entrances for boys and girls on opposite sides of the building.

“The genders may have been separated by doorways, but their education fell under the doctrine that knowledge is power, a phrase carved into the front of the building for all to see,” a press release from BOCES said.

Though the building was once home to all the grades in the school district, the district expanded and it eventually housed only middle school students. When those kids were moved into the Earl L. Vandermeulen High School building on Old Post Road, where they remain today, the historical building was left behind.

Port Jefferson’s old high school on Spring Street was made of wood and burned down on July 4, 1913. Photo from the Port Jefferson Village Digital Archive
Port Jefferson’s old high school on Spring Street was made of wood and burned down on July 4, 1913. Photo from the Port Jefferson Village Digital Archive

Eastern Suffolk BOCES stepped in during the late 1990s. Sean Leister, Port Jefferson’s assistant superintendent for business, said the school district began leasing the building to BOCES in March 1997. And according to BOCES, it has been providing special education services at the Jefferson Academic Center since 1998.

In 2007, the deteriorating Spring Street building got a little lift — district voters overwhelmingly approved a $5.2 million bond to renovate the building, which came with a renewed 10-year lease, the yearly rent of which covered the cost of the improvements. Those included replacing the gym floor, piping and the boilers; improving site drainage; doing work on the electrical system and the foundation; and making the building more handicapped-accessible with additional toilets, a wheelchair lift and an elevator.

The renovations have kept the Spring Street school going strong — it is the oldest school in Suffolk County that still operates as such.

To 100 years more.

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Sedentary lifestyle contributes

A good follow-up to last week’s acute pancreatitis article is one on gallstones. As I wrote, gallstones are the most significant contributing factor to the development of acute pancreatitis. Like pancreatitis, gallstones are a very common gastrointestinal disease; they affect up to 20 million Americans between the ages 20 of and 74, with a more than two-times increased occurrence in women than in men, according to the NHANES III survey (1). There are two types of gallstones, the majority of which are cholesterol stones — 80 percent occurrence — with pigment stones — 20 percent occurrence — making up the remainder.

Common symptoms

Gallstones may be asymptomatic; however, when gallstones block either the cystic or common bile ducts, symptoms occur. Symptoms include abdominal pain, exacerbated by meals, that is dull or crampy and lasts one to five hours; jaundice, which includes yellowing of skin and eyes; nausea and vomiting; rapid heart rate; hypotension — low blood pressure — and fever (2).

Tests used for diagnosis

Blood tests include complete blood count where there may be a rise in white blood cells; liver enzymes; and pancreatic enzymes — lipase and amylase. In general, diagnostic tests that have more accuracy are the endoscopic ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP). However, these are invasive tests. Less accurate but non-invasive tests include abdominal x-ray, ultrasound and CAT Scan (CT). The tests used also depend on where the stone may be located. Hepatobiliary (HIDA) scans are accurate if the stone is located in the cystic duct. And magnetic resonance retrograde cholangiopancreatography (MRCP) is used if the stone is thought to be located in the common bile duct (2).

What are the risk factors?

There are a multitude of risk factors. Some of these are modifiable, whereas others are not. The modifiable ones include obesity, measured by body mass index (BMI); rapid weight loss; fat consumption; hormone replacement therapy (HRT); oral contraceptives; decreased physical activity; Crohn’s disease and certain drugs. One non-modifiable risk factor is age; the older we get, the higher the risk, with 40 years of age being the demarcation line (3). Other risk factors are gender — females are more predisposed — pregnancy; and family history (4).

Let’s look at the evidence.

Obesity

Again, as with acute pancreatitis, obesity may play an important role. Obesity is not age-discriminant; it can impact both adults and children. The reason obesity is implicated is potentially due to bile becoming supersaturated (5). Bile is a substance produced in the liver and stored in the gallbladder. Bile aids in the digestion or breakdown of fats in the small intestines. Crystals may form, creating cholesterol gallstones from the bile.

Body Mass Index

A body mass index of greater than 30 kg/m2 is considered obese. In a meta-analysis of two prospective, forward-looking observational trials — Copenhagen General Population Study and the Copenhagen City Heart Study — those in the highest quintile of BMI were almost three times as likely to experience symptomatic gallstones compared to those who were in the lowest quintile (6). The highest quintile was those who had a mean BMI of 32.5 kg/m2 and thus were obese, whereas those in the lowest quintile had a mean BMI of 20.9 kg/m2. This is a comparison of ideal to obese BMI. Not surprisingly, since women in general have a higher risk of gallstones, they also have a higher risk when their BMI is in the obese range compared to men, a 3.36-fold increase and 1.51-fold increase, respectively.

Also, the research showed that for every 1 kg/m2 increase in BMI, there was a 7 percent increase in the risk of gallstones. Those who had genetic variants that increased their likelihood of an elevated BMI had an even greater increase in gallstone risk —17 percent —  per 1 kg/m2. In the study population of approximately 77,000, more than 4,000 participants became symptomatic for gallstones.

Gallstones in children

Sadly, obese children are not immune to gallstones, even though they are young. In a prospective observational study based on Kaiser Permanente data from Southern California, children who were overweight had a twofold increased risk of gallstones (7). But if that is not enough, girls who were extremely obese had a higher propensity for gallstones, similar to women in the previous study, with a  greater than sevenfold increase compared to a still very substantial greater-than-threefold increase for obese boys. Hispanic children were affected the most. The age range in this study was between 10 and 19 years old. Obesity is a disease that is blind to age.

Physical activity

We know physical activity is very important to stave off many diseases, but in this case, the lack of physical activity can be detrimental. In the Physicians’ Health Study, a prospective observational trial, those in the lowest quintile of activity between the ages of 40 and 64 had a 72 percent increased risk of gallstone formation, and those 65 and older had a 33 percent increased risk. (8). Also, men who were 65 and older and watched television more than six hours a week were at least three times as likely to have gallstones as those who watched fewer hours. There was a substantial increased risk for those under 65, as well, though to a slightly lesser degree.

Diabetes rears its ugly head

Just like with obesity, diabetes is almost always a culprit for complications. In a prospective observational study, those with diabetes were at a significant 2.55-times greater risk of developing gallstones than those without (9). Again, women had a higher propensity than men, but both had significant increases in the risk of gallstone formation, 3.85-times and 2.03-times, respectively. There were almost 700 participants in this study. The researchers believe that an alteration in glucose — sugar — metabolism may create this disease risk.

Hormone Replacement Therapy

If you needed another reason to be leery of hormone replacement therapy (HRT), then gallstones might be it. In a prospective observational trial, women who used HRT, compared to those who did not, had a 10 percent increased risk in cholecystectomy — removal of the gallbladder — to treat gallstones (10). Though this may not sound like a large increase, oral HRT increased the risk 16 percent, and oral estrogen-only therapy without progestogens increased the risk the most — 38 percent. Transdermal HRT did not have a significantly increased risk.

It is never too early or too late to treat obesity before it causes, in this case, gallstones. With a lack of exercise, obesity is exacerbated and, not surprisingly, so is symptomatic gallstone formation. Diabetes needs to be controlled to prevent complications. HRT, unless menopausal symptoms are unbearable, continues to show why it may not be a good choice. Next week, we will look at the complications of gallstones and how to prevent them.

References:

(1) Gastroenterology. 1999;117:632. (2) emedicine.medscape.com. (3) J Hepatol. 1993;18 Suppl 1:S43. (4) uptodate.com. (5) Best Pract Res Clin Gastroenterol. 2014 Aug;28:623-635. (6) Hepatology. 2013 Dec;58:2133-41. (7) J Pediatr Gastroenterol Nutr. 2012;55:328-333. (8) Ann Intern Med. 1998;128:417. (9) Hepatology. 1997;2:787. (10) CMAJ. 2013;16;185:549-50.

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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For Annie Heroux, it was love at first sight, at least as far as her career was concerned. During her days of studying at the Universite de Montreal, she took a course in crystallography — the study of the structure of small objects by looking at a crystallized arrangement of their atoms.

Even before the class began, she read the entire book. When she saw the professor, Francois Brisse, she said, “This is what I want to do” in graduate school. And so she did.

“I never planned for it,” she said. “It just happened.”

For her graduate work, Heroux performed crystallography work on polymers like kevlar. Eventually, her interest took her to Brookhaven National Laboratory, where she’s been for the last 13 years.

A beamline scientist, Heroux provides a supporting role to many of the users from around the world who come to BNL to see if they can make a link between the structure of something small that often happens inside a cell and its function.

“It is like knowing the shape of the tiny gears in a watch — OK, an antique watch with gears — and then desiring to know how the gears move each other to count down time, or move a muscle or have a thought,” explained BNL colleague and fellow Beamline Scientist Howard Robinson.

Recently, Heroux worked with Scott Bailey, an associate professor in the Johns Hopkins Bloomberg School of Public Health’s Department of Biochemistry and Molecular Biology. Bailey explored how bacteria were able to recognize and destroy viruses.

Heroux helped provide the first picture of the RNA and DNA of a molecular tool called Cascade, which protects the bacteria.

Cascade, an 11-protein genetic security system that can only function if each part is working correctly, uses short strands of bacterial RNA to scan its DNA to see if the genetic blueprints come from something else that might be trying to corrupt its system. If the RNA recognizes something other than its own code, it breaks down the DNA.

Heroux helped explore more conditions to get better crystals with better diffraction qualities — or ways that light bends.

In this research, which was published in August in the journal Science, Bailey and his collaborators found that the RNA scans the DNA in a way similar to how we look through text for a single word. The Cascade has a template to find its compatible counterpart.

In general, Heroux said her role is to make sure that everything works the way it should at the beamline. She “goes through the steps to figure out all the things that can go wrong during an experiment.”

After she helps with experiments, she returns to “crunch the numbers on the computer.”

While she doesn’t have her own lab or pursue her own research agenda, she does have an opportunity to try to figure out new ways to solve the structure of a molecule in a different way.

Heroux is looking forward to the opportunities presented by the NSLS II, the second generation of synchrotron that will open officially in 2015. The beam, which is 10,000 times brighter than the original, will create new opportunities and new challenges.

“The beamline will be so bright that we will modify the way we do experiments,” she said. The X-rays have the potential to destroy the crystals. The experiments will have to occur at a faster speed and may require more crystals to get a full data set.

Heroux enjoys the process of collaborating with scientists on their projects.

“Most scientists are pretty centered over what they want to do,” she said. “What I find interesting is that, by collaborating with all kinds of different groups, I get to see all kinds of different problems. It’s never the same thing.”

A resident of Shirley, which is only seven minutes from the lab, Heroux lives with her partner, Matt Cowan, a computer expert. Heroux, who is originally from Montreal, met Cowan through her work.

The couple have three children: Viviane Trudel, 21, Florence Trudel, 18 and Ethan Cowan, 10.

Heroux enjoys walking through parks with a mycology club, which searches for and identifies mushrooms. She calls cooking her “big relaxation,” and has tried her hand at Indian and Mexican food. She has also made her own sushi.

As for her work, she still is excited about seeing the structure of objects.“You collect data, which are spots on your detector and, if you’re lucky, a couple of hours later, you see the structure popping up,” she said. “That is always exciting, no matter what the structure is.”

 

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Everyone has heard of pancreatic cancer, but pancreatitis is a significantly more common disease in gastroenterology and seems to be on an upward projection. Ironically, this disease gets almost no coverage in the general press. In the United States, it is among the top reasons for patients to be admitted to the hospital (1).

Now that I have your attention, let’s define pancreatitis. A rudimentary definition is an inflammation of the pancreas. There are both acute and chronic forms. We are going to address the acute – abrupt and of short duration – form. There are three acute types: mild, moderate and severe. Those with the mild type don’t have organ failure, whereas those with moderate acute pancreatitis experience short-term or transient (less than 48 hours) organ failure. Those with the severe type have persistent organ failure. One in five patients present with moderate or severe levels (2).

What are the symptoms?

In order to diagnosis this disease, the American College of Gastroenterology guidelines suggests that two of three symptoms be present. The three symptoms include severe abdominal pain; increased enzymes, amylase or lipase, that are at least three times greater than normal; and radiologic imaging (ultrasound, CT, MRI, abdominal and chest X-rays) that shows characteristic findings for this disease (3). Most of the time, the abdominal pain is epigastric, and it may also present with pain in the right upper quadrant of the abdomen (4). Approximately 90 percent of patients may also experience nausea and vomiting (5). In half of patients, there may also be pain that radiates to the back.

What are the risk factors?

There is a multitude of risk factors for acute pancreatitis. These include gallstones, alcohol, obesity and, to much lesser degree, drugs. Gallstones and alcohol may cause up to 75 percent of the cases (2). Many of the other cases of acute pancreatitis are considered idiopathic (of unknown causes). Although medications are potentially responsible for between 1.4 percent and 5.3 percent of cases, making it rare, the number of medications implicated is diverse (6) (7). These include certain classes of diabetes therapies, some antibiotics – Flagyl (metronidazole) and tetracycline – and immunosuppressive drugs used to treat ailments like autoimmune diseases. Even calcium may potentially increase the risk.

Obesity effects

When given a multiple-choice question for risk factors that includes obesity as one of the answers, it’s a safe bet to choose that answer. Pancreatitis is no exception. However, in a recent study, using the Swedish Mammography Cohort and the Cohort of Swedish Men, results showed that central obesity is an important risk factor, not body mass index or obesity overall (8). In other words, it is fat in the belly that is very important, since this may increase risk more than twofold for the occurrence of a first-time acute pancreatitis episode.

Those who had a waist circumference of greater than 105 cm (41 inches) experienced this significantly increased risk compared to those who had a waist circumference of 75 to 85 cm (29.5 to 33.5 inches). The association between central obesity and acute pancreatitis occurred in both gallbladder-induced and nongallbladder-induced disease. There were 68,158 patients involved in the study with a median duration of 12 years. Remember that waistline is measured not from the hips, but rather from the navel. This may be surprising wake-up call for some.

Mortality risks

What makes acute pancreatitis so noteworthy and potentially dangerous is that the rate of organ failure and mortality is surprisingly high. One study found that the risk of mortality was 5 percent overall. This statistic broke out into a smaller percentage for mild acute pancreatitis and a greater percentage for severe acute pancreatitis, 1.5 percent and 17 percent respectively (9). This was a prospective (forward-looking) observational trial involving 1,005 patients.

However, in another study, when patients were hospitalized for this disease, the mortality rate was even higher at 10 percent overall (10).

Diabetes risks

The pancreas is a critical organ for balancing glucose (sugar) in the body. In a recent meta-analysis (involving 24 observational trials), the results showed that more than one-third of patients diagnosed with acute pancreatitis went on to develop pre-diabetes or diabetes (11). Within the first year, 15 percent of patients were newly diagnosed with diabetes. After five years, it was even worse; the risk of diabetes increased by 2.7-fold. This is scary, considering that diabetes has become a pandemic. If we can reduce the risk of pancreatitis, we may also help to reduce the risk of diabetes.

Surgical treatments

Gallstones and gallbladder sludge are major risk factors, accounting for 35 to 40 percent of acute pancreatitis incidence (12). Gallstones are thought to cause pancreatitis by temporarily blocking the duct shared by the pancreas and gallbladder that leads into the small intestine. When the liver enzyme ALT is elevated threefold (measured through a simple blood test), it has a positive predictive value of 95 percent that it is indeed gallstone-induced pancreatitis (13).

If it is gallstone-induced, surgery plays an important role in helping to resolve pancreatitis and prevent recurrence of acute pancreatitis. In a recent study, results showed that surgery to remove the gallbladder was better than medical treatment when comparing hospitalized patients with this disease (14). Surgery trumped medical treatment in terms of outcomes, complication rates, length of stay in the hospital and overall cost for patients with mild acute pancreatitis. This was a retrospective (backward-looking) study with 102 patients.

Can diet have an impact?

The short answer is: yes. What foods specifically? In a large, prospective observational study, results showed that there was a direct linear relationship between those who consumed vegetables and a decreased risk of nongallstone acute pancreatitis (15). For every two serving of vegetables, there was 17 percent drop in the risk of pancreatitis. Those who consumed the most vegetables – the highest quintile (4.6 servings per day) – had a 44 percent reduction in disease risk, compared to those who were in the lowest quintile (0.8 servings per day). There were 80,000 participants involved in the study with an 11-year follow-up. The authors surmise that the reason for this effect with vegetables may have to do with their antioxidant properties, since acute pancreatitis increases oxidative stress on the pancreas.

References:

(1) Gastroenterology. 2012;143:1179-1187. (2) www.uptodate.com. (3) Am J Gastroenterol. 2013;108:1400-1415. (4) JAMA. 2004;291:2865-2868. (5) Am J Gastroenterol. 2006;101:2379-2400. (6) Gut. 1995;37:565-567. (7) Dig Dis Sci. 2010;55:2977-2981. (8) Am J Gastroenterol. 2013;108:133-139. (9) Dig Liver Dis. 2004;36:205-211. (10) Dig Dis Sci. 1985;30:573-574. (11) Gut. 2014;63:818-831. (12) Gastroenterology. 2007;132:2022-2044. (13) Am J Gastroenterol. 1994;89:1863-1866. (14) Am J Surg online. 2014 Sept. 20. (15) Gut. 2013;62:1187-1192.

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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Ominous forecasts start a cascade of reactions, from a race through the supermarket for canned goods and water to trips to the hardware store for batteries and flashlights to a rush to the gas station to fill up before the possibility of an interruption in the supply line.

Stephanie Hamilton is determined to turn predictions of an approaching storm into a new kind of action plan for utilities.

A Smarter Grid R&D Manager at Brookhaven National Laboratory, Hamilton recently received a $336,000 grant from the New York State Energy and Research Development Authority to work with two utilities in upstate New York, Orange and Rockland Utilities and Central Hudson Gas and Electric. She would like to help these utilities gain a better understanding of how to interpret and use weather data to develop a plan for approaching storms.

The elements of new information in the BNL study will include streaming radar that offers forecasts in a range of 1.5 kilometers.

“What this will tell them is where we think the storm is going to be, the volume of the precipitation and how long that might continue,” Hamilton said.

That kind of specific knowledge of a storm will aid companies in understanding where to put reserves in place by reaching out to other companies through a mutual aid assistance program in states that might not be as affected by a storm.

When Hurricane Sandy hit, for example, Orange and Rockland Utilities had over 4,000 workers come to help restore power. Wisconsin Gas and Electric sent crews to Long Island to aid in the storm recovery.

Hamilton and her colleagues are working on building a toolkit that will help utility personnel use weather information they currently don’t have.

“Our expectation is that by having the information and new tools,” these companies will be able to understand “how severe weather will impact their systems.”

— Stephanie Hamilton

Hamilton said she herself isn’t the weather expert: she is relying on the meteorological expertise of BNL scientists Michael Jensen and Scott Giangrande. She is hoping to bring together the skills at understanding severe atmospheric conditions with an awareness of the vulnerable points on an electric grid.

Hamilton’s former supervisor, Gerald Stokes, who is now a visiting professor in the Department of Technology and Society at Stony Brook University, praised her work and her approach. Hamilton is “well regarded in the smart grid and utility community and is seen as one of the pioneers in that area,” he said.

The BNL study is one of seven such efforts NYSERDA is sponsoring with a total of $3.3 million to help utilities prepare for and react to severe weather events.

“As we continue to witness the impacts of extreme weather, it is more important than ever to invest in making our energy infrastructure stronger and smarter,” Gov. Andrew Cuomo said in a statement.

Hamilton hopes this is among the first steps in what could be a lengthy and productive local analysis of the vulnerabilities of the system to various disruptions. Some utility poles might be in areas where the ground becomes saturated with only a few inches of rain, depending on the local conditions and the ability of the vegetation in the area to soak up any accumulations.

When this project ends, the BNL team will try to demonstrate the tool at the utility with their existing procedures to validate the model and see how it can be used, she said.

Down the road, the utilities could integrate this kind of analysis with a pole-by-pole understanding of vulnerabilities to specific weather conditions.

The utilities have a financial incentive to bring systems damaged by a storm back online. Hamilton said a one hour reduction in storm response could save Orange and Rockland Utilities about $100,000 to $200,000.

A resident of Manorville, Hamilton lives with her partner John York, a retired Army lieutenant colonel and an IT expert working with TIAA-CREF in New Jersey as a business analyst for computing systems. Hamilton has enjoyed her three and a half years at BNL after growing up in south Georgia and spending much of her career in western states, including California, Washington and Wyoming.

As for her work, she feels at home at BNL.

“This is really a culmination of all the things I’ve ever wanted to do,” she said. She relishes the opportunity to “move the industry ahead. Making [utilities] more reliable and resilient is the key to our economy.”

 

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Soy may decrease risk if consumed in higher quanitities

NFL players are wearing pink shoes and other sportswear this month, making a fashion statement to highlight Breast Cancer Awareness Month. This awareness is critical, since annual breast cancer incidence in the U.S. is 230,000 cases, with approximately 40,000 patients, or 17 percent, dying from this disease each year (1). The good news is that from 1997 to 2008 there was a trend toward decreased incidence by 1.8 percent (2).

We can all agree that screening has merit. The commercials during NFL games tout that women in their 30s and early 40s have discovered breast cancer with a mammogram, usually after a lump was detected. Does this mean we should be screening earlier?

Screening guidelines are based on the general population that is considered “healthy,” meaning no lumps were found, nor is there a personal or family history of breast cancer. All guidelines hinge on the belief that mammograms are important, but at what age? Here is where divergence occurs; experts can’t agree on age and frequency. The U.S. Preventive Services Task Force recommends mammograms starting at 50 years old, after which time they should be done every other year (3). The  American College of Obstetricians and Gynecologists recommends mammograms start at 40 years old and be done annually (4). Your decision should be based on a discussion with your physician.

The best way to treat breast cancer – and just as important as screening – is prevention, whether it is primary, preventing the disease from occurring, or secondary, preventing recurrence. We are always looking for ways to minimize risk. What are some potential ways of doing this? These may include lifestyle modifications, such as diet, exercise, obesity treatment and normalizing cholesterol levels. Additionally, although results are mixed, it seems that bisphosphonates do not reduce the risk of breast cancer or its recurrence.

Let’s look at the evidence.

Bisphosphonates

Bisphosphonates include Fosamax (alendronate), Zometa (zoledronic acid) and Boniva (ibandronate) used to treat osteoporosis. Do they have a role in breast cancer prevention? It depends on the population, and it depends on study quality.

In a meta-analysis involving two randomized controlled trials, results showed there was no benefit from the use of bisphosphonates in reducing breast cancer risk (5). The population used in this study involved postmenopausal women who had osteoporosis, but who did not have a personal history of breast cancer. In other words, the bisphosphonates were being used for primary prevention. The study was prompted by previous studies that have shown antitumor effects with this class of drugs. This analysis involved over 14,000 women ranging in age from 55 to 89. The two trials were FIT and HORIZON-PFT, with durations of 3.8 and 2.8 years, respectively. The FIT study involved alendronate and the HORIZON-PFT study involved zoledronic acid, with these drugs compared to placebo. The researchers concluded that the data were not evident for the use of bisphosphonates in primary prevention of invasive breast cancer.

In a previous meta-analysis of two observational studies from the Women’s Health Initiative, results showed that bisphosphonates did indeed reduce the risk of invasive breast cancer in patients by as much as 32 percent (6). These results were statistically significant. However, there was an increase in risk of ductal carcinoma in situ (precancer cases) that was not explainable. These studies included over 150,000 patients with no breast cancer history. The patient type was similar to that used in the more current trial mentioned above. According to the authors, this suggested that bisphosphonates may have an antitumor effect. But not so fast!

The disparity in the above two bisphosphonate studies has to do with trial type. Randomized controlled trials are better designed than observational trials. Therefore, it is more likely that bisphosphonates do not work in reducing breast cancer risk in patients without a history of breast cancer or, in other words, in primary prevention.

In a third study, a meta-analysis (group of 36 post-hoc analyses – after trials were previously concluded) using bisphosphonates, results showed that zoledronic acid significantly reduced mortality risk, by as much as 17 percent, in those patients with early breast cancer (7). This benefit was seen in postmenopausal women, but not in premenopausal women. The difference between this study and the previous study was the population. This was a trial for secondary prevention, where patients had a personal history of cancer.

However, in a RCT, the results showed that those with early breast cancer did not benefit overall from zoledronic acid in conjunction with standard treatments for this disease (8). The moral of the story: RCTs are needed to confirm results, and they don’t always coincide with other studies.

Exercise

We know exercise is important in diseases and breast cancer is no exception. In a recent observational trial, exercise reduced breast cancer risk in postmenopausal women significantly (9). These women exercised moderately; they walked four hours a week. The researchers stressed that it is never too late to exercise, since the effect was seen over four years. If they exercised previously, but not recently, for instance, 5 to 9 years ago, no benefit was seen.

To make matters worse, only about one-third of women get the recommended level of exercise every week: 30 minutes for five days a week. Once diagnosed with breast cancer, women tend to exercise less, not more. The NFL, which does an admirable job of highlighting Breast Cancer Awareness Month, should go a step further and focus on the importance of exercise to prevent breast cancer or its recurrence, much as it has done to help motivate kids to exercise with its “Play 60” campaign.

Soy intake

Contrary to popular belief, soy may be beneficial in reducing breast cancer risk. In a recent meta-analysis (a group of eight observational studies), those who consumed more soy saw a significant reduction in breast cancer compared to those who consumed less (10). There was a dose-response curve among three groups: high intake of >20 mg per day, moderate intake of 10 mg and low intake of <5 mg. Those in the highest group had a 29 percent reduced risk, and those in the moderate group had a 12 percent reduced risk, when compared to those who consumed the least. Why have we not seen this in U.S. trials? The level of soy used in U.S. trials is a fraction of what is used in Asian trials. The benefit from soy is thought to come from isoflavones, plant-rich nutrients.

Western versus Mediterranean diets

In an observational study, results showed that, while the Western diet increases breast cancer risk by 46 percent, the Spanish Mediterranean diet has the inverse effect, decreasing risk by 44 percent (11). The effect of the Mediterranean diet was even more powerful in triple-negative tumors, which tend to be difficult to treat. The authors concluded that diets rich in fruits, vegetables, beans, nuts and oily fish were potentially beneficial.

Hooray for Breast Cancer Awareness Month stressing the importance of mammographies and self-breast exams. However, we need to give significantly more attention to prevention of breast cancer and its recurrence. Through potentially more soy intake, as well as a Mediterranean diet and modest exercise, we may be able to accelerate the trend toward a lower breast cancer incidence.

References:

(1) CA Cancer J Clin. 2013;63:11-30. (2) J Natl Cancer Inst. 2011;103:714-736. (3) Ann Intern Med. 2009;151:716-726. (4) Obstet Gynecol. 2011;118:372-382. (5) JAMA Inter Med online. 2014 Aug. 11. (6) J Clin Oncol. 2010;28:3582-3590. (7) 2013 SABCS: Abstract S4-07. (8) Lancet Oncol. 2014;15:997-1006. (9) Cancer Epidemiol Biomarkers Prev online. 2014 Aug. 11. (10) Br J Cancer. 2008;98:9-14. (11) Br J Cancer. 2014;111:1454-1462.

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, visit www.medicalcompassmd.com and/or consult your personal physician.

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In the 1970s, when he was in graduate school at New York University, Thomas Gingeras said his late mother, Barbara Lammons, described him as a vet for flies. While earning his Ph.D., Gingeras brought home bottles of one of the more common scientific test subject, the fruit fly, and stored them in a bathroom.

Almost four decades later, Gingeras, a professor at Cold Spring Harbor Laboratory, still works with flies, although he doesn’t need to bring any of them to his home on the campus at the laboratory. Instead, he is one of the leaders in a group called Encode, for the encyclopedia of DNA elements.

The Encode project includes scientists from around the world and provides a detailed catalog of genetic elements.

The latest version, called modEncode, for the Model Organism Encyclopedia of DNA Elements, compares genetic elements of humans to those of flies and the roundworm, two of the more actively studied by science.

Using billions of pieces of information including DNA base pairs and messenger RNA, scientists were able to explore the overlap in genetic machinery among members of species with considerably different lives.

“What we see,” Gingeras said, “are patches of things where the sequences that are known to carry out specific functions relate to one another.” These results were recently published in the journal Nature.

He likened the study to an examination of paintings. Looked at from a distance, the way a fly, worm and human might be seen, the end product appears different. “When you look at small areas, you can see” similarities among the paintings.

By finding overlap, scientists can hone in on ways to repair damage and provide additional genetic targets to cure human disease. “This points us in the direction of setting these at the top of the priority list,” said Gingeras. One of the primary paths pharmaceutical companies pursue is that “they look to find a disease state that is closely mimicking what is happening in humans. They look to see if the cause is similar, in their genes and regulatory regions.”

In his lab, Gingeras has five people who do benchwork, producing genetic data. Another five dedicate their time to making sense of that information, plugging bits of data into computers and looking for meaningful overlaps. Gingeras divides his time between analyzing and interpreting the data, writing for grant money and summarizing results in research papers.

Gingeras said the Encode group has been through some battles in the scientific community, especially when they first proposed the idea that the genes that don’t code for a specific element still might have a function for the organism and for the cell.

“The predominant idea when the human genome sequence was deciphered is that only a small fraction of the genome was functional,” about 2 percent, Roderic Guigo Serra, coordinator of the Bioinformatics and Genomics Program at the Center for Genomic Regulation in Barcelona explained in an email. “Gingeras “demonstrated that the fraction of the genome that is transcribed is much larger,” closer to 60 percent or more. Initially, Gingeras’s results were viewed with skepticism; they are now “widely accepted.”

Gingeras admitted that the early criticism bothered him.

“I took it very personally,” he said. “Not too long into this process, it dawned on me that it doesn’t make any difference what anybody thinks. If it’s right, [other scientists] will see it for themselves.”

Serra, who started collaborating with Gingeras more than a decade ago, said his colleague has “amazing energy,” and can call him to discuss their work at almost any hour of the day. This, he said, has been challenging but also motivating for Serra. Gingeras “has the insight to anticipate the questions that will become important before others,” he said.

Gingeras and his wife Hillary Sussman, who is the executive editor of the journal Genome Research at CSHL, have a 12-year-old daughter, Noa Sussman and a 5-year-old, Arie Anna Gingeras.

As for his work, Gingeras said the next steps in the analysis of genomes could include other organisms.

“The intention has been, all along, to provide a blueprint of what you could do on any organism to understand better what the component parts of the organism are,” he said. “This effort is meant to be a model case of what you could do for all organisms. The next step is to do the same thing for other organisms or study systems.”

 

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