178 04 MAR 2014 / Compiled by Ralph Turchiano

 

• Detailed research references and further affiliations on each article are posted at http://www.healthreserachreport.me .

 

 

In This issue:

• HPV eradicated by AHCC supplement, preclinical study suggests
• Shock-absorbing ‘goo’ discovered in bone
• Texas researcher: Peaches inhibit breast cancer metastasis in mice
• Brain degeneration in Huntington’s disease caused by amino acid deficiency ( Cysteine )
• Beer marinade could reduce levels of potentially harmful substances in grilled meats
• More severe heart disease found in patients with vitamin D deficiency
• One size does not fit all: Dietary guidelines for choline may be insufficient
• Eating fruits and vegetables linked to healthier arteries later in life
• UNC researchers show cancer chemotherapy accelerates ‘molecular aging’
• Too many diet drinks may spell heart trouble for older women
• Can antibiotics cause autoimmunity?
• Breast milk and diet up to 2 years old: a means of preventing the risk of child obesity
• Adult Tonsillectomy Complications and Health Care Expenses
• Key chocolate ingredients could help prevent obesity, diabetes
• Coffee consumption reduces mortality risk from liver cirrhosis
• Chowing down on watermelon could lower blood pressure
• Higher total folate intake may be associated with lower risk of exfoliation glaucoma

 

HPV eradicated by AHCC supplement, preclinical study suggests

Japanese mushroom extract active hexose correlated compound (AHCC) may have role in prevention HPV-related cancers

(March 23, 2014, Beaverton, OR) Treating cervical cancer cells with AHCC led to the eradication of HPV, human papillomavirus, as well as a decrease in the rate of tumor growth in-vitro and in-vivo, in research presented at the Society of Gynecological Oncology 45th Annual Meeting on Women’s Cancer in Tampa, Florida. The study was led by Dr. Judith A. Smith, Pharm.D., at the University of Texas Health Science Center (UTHealth) Medical School at Houston.

In the study cervical cancer cells were treated with AHCC and incubated for 72 hours with sampling every 24 hours. The study was then repeated in two orthotopic mouse models, one HPV positive and other HPV negative control. The HPV expression was eradicated with once daily AHCC dosing for 90 days with durable response after 30 day observation off treatment. Dr. Smith then repeated the study to confirm findings and added sampling for correlative testing of immune markers to determine the mechanism by which AHCC eradicates the HPV virus.

These data suggest AHCC can eliminate HPV infections and may have a role in the prevention of HPV-related cancers. A confirmatory pilot study in HPV+ women is underway at UTHealth Women’s Center.

“The results of this study were very encouraging,” said Dr. Smith, Associate Professor at the UTHealth Medical School. “This study, initiated in 2008, shows that by itself AHCC has the potential to treat the HPV infection,” she said. Smith’s previous study evaluated AHCC integration with common chemotherapy agents used for the treatment of ovarian cancer, to screen for potential drug interactions and improvement in activity.

AHCC works as an immunotherapy, which is a treatment that uses a body’s own immune system to help fight disease. Human and in-vivo studies have shown that AHCC increases the number and/or activity of Natural Killer (NK) cells, dendritic cells, and cytokines, which enable the body to effectively respond to infections and block the proliferation of tumors. http://ahccresearch.com/index.html

HPV (human papilloma virus) is the most common sexually transmitted virus in the United States. Up to 70% of sexually active adults will acquire HPV at some point in their lives. Human papillomavirus DNA has been detected in 99.7% of cervical cancer biopsies, yielding the largest causative relationship of any cancer. (1) According to the CDC several other types of cancer are also HPV related, including: 95% of anal cancer; 60% of oropharyngeal cancer; 65% of vaginal cancer; 50% of vulvar cancer; and 35% of penile cancer.

“I was intrigued by research presented at the annual AHCC symposium in Sapporo (2) showing the immune modulating effect of AHCC on other rare infections, and was eager to study the possibilities in treating the HPV infection associated with cervical cancer,” said Dr. Smith.

“AHCC is a common, well tolerated nutritional supplement that has been used for decades in Japan, I am very excited to be pursuing a nutritional approach to trying to find a treatment for HPV infections,” said Dr. Smith, whose research is on drug development for gynecologic cancers and conditions with a specific focus on drug interactions/drug resistance and integration of herbal and nutritional supplements for treatment of cancer.

“We had previously demonstrated an antiretroviral regimen that successfully eradicated the HPV infection but wanted to develop a more benign protocol, since these medications have a number of side effects,” Dr. Smith continued.

Shock-absorbing ‘goo’ discovered in bone

Latest research shows that the chemical citrate – a by-product of natural cell metabolism – is mixed with water to create a viscous fluid that is trapped between the nano-scale crystals that form our bones.

This fluid allows enough movement, or ‘slip’, between these crystals so that bones are flexible, and don’t shatter under pressure. It is the inbuilt shock absorber in bone that, until now, was unknown.

If citrate leaks out, the crystals – made of calcium phosphate – fuse together into bigger and bigger clumps that become inflexible, increasingly brittle and more likely to shatter. This could be the root cause of osteoporosis.

The team from Cambridge’s Department of Chemistry used a combination of NMR spectroscopy, X-ray diffraction, imaging and high-level molecular modelling to reveal the citrate layers in bone.

They say that this is the start of what needs to be an entire shift in focus for studying the cause of brittle bone diseases like osteoporosis, and bone pathologies in general. The study is published today in the journal Proceedings of the National Academy of Sciences.

“Bone mineral was thought to be closely related to this substance called hydroxyapatite. But what we’ve shown is that a large part of bone mineral – possibly as much as half of it in fact – is made up of this goo, where citrate is binding like a gel between mineral crystals,” said Dr Melinda Duer, who led the study.

“This nano-scopic layering of citrate fluid and mineral crystals in bone means that the crystals stay in flat, plate-like shapes that have the facility to slide with respect to each other. Without citrate, all crystals in bone mineral would collapse together, become one big crystal and shatter.

“It’s this layered structure that’s been missing from our knowledge, and we can now see that without it you’re stuffed.”

Duer compares it to two panes of glass with water in the middle, which stick together but are able to slide: “it’s the same thing in these flat bone crystals. But you’ve got to have something that keeps the water there, stops it from drying out and stops the plates from either flying apart or sticking fast together. We now know that thing is citrate.”

Citrate is a ‘spidery’ molecule with four arms, all of which can bond easily to calcium – which bone is packed with, explains Duer. This means that citrate can hold the mineral crystals together at the same time as preventing them from fusing, while trapping the water that allows for the slippery movement which provides bone flexibility. “Without citrate, water would just flow straight through these gaps,” she said.

The body actually delivers bone calcium wrapped in citrate, to prevent it fusing with phosphate and forming large solid – and brittle – mineral crystals in the wrong places. Bone tissue has a protein mesh with holes where the calcium is deposited. In healthy tissue, the holes are very small, so that when the calcium is deposited, the citrate that comes with it can’t escape and is trapped between crystals – creating the flexible layers of fluid and bone plates.

As people age or suffer repeated bone trauma, the protein mesh isn’t repaired so well by the cells that try to replace damaged tissue, but often end up chewing away tissue faster than it can be re-deposited. This causes progressively larger holes in the protein mesh, citrate fluid escapes and crystals fuse together.

What happens then is pure chemistry, says Duer, with little biological control.

The body instigates a form of biological control through the tiny holes in the protein mesh that trap the citrate fluid, along with other molecules that normally control the deposit of mineral. These small spaces force the molecules to be involved with the forming mineral, controlling the process. But if you haven’t got the confined space the chemical reactions spiral out of control.

“In the bigger holes in damaged tissue, pure chemistry takes over. Pretty much the moment calcium and phosphate touch, they form a solid. You end up with these expanding clumps of brittle crystal, with water and citrate relegated to the outside of them,” she said.

“In terms of chemistry, that solid clump of mineral is the most stable structure. Biomechanically, however, it’s hopeless – as soon as you stand on it, it shatters. If we want to cure osteoporosis, we need to figure out how to stop the bigger holes forming in the protein matrix.”

The study is the first in a series of findings, with other studies from the team’s work on bone chemistry expected to come out later in the year

 

Texas researcher: Peaches inhibit breast cancer metastasis in mice

COLLEGE STATION – Lab tests at Texas A&M AgriLife Research have shown that treatments with peach extract inhibit breast cancer metastasis in mice.

AgriLife Research scientists say that the mixture of phenolic compounds present in the peach extract are responsible for the inhibition of metastasis, according to the study, which was this month published in the Journal of Nutritional Biochemistry.

“Cancer cells were implanted under the skin of mice with an aggressive type of breast cancer cells, the MDA-MB-435, and what we saw was an inhibition of a marker gene in the lungs after a few weeks indicating an inhibition of metastasis when the mice were consuming the peach extract,” said Dr. Luis Cisneros-Zevallos, a food scientist for AgriLife Research in College Station. “Furthermore, after determining the dose necessary to see the effects in mice, it was calculated that for humans it would be equivalent to consuming two to three peaches per day.”

This is very important because it can be translated into something that is also beneficial for people, he added.

This work builds upon previous work at AgriLife Research released a few years ago, which showed that peach and plum polyphenols selectively killed aggressive breast cancer cells and not the normal ones, Cisneros-Zavallos said.

The previous work as well as the present one was conducted by Cisneros-Zevallos, Dr. David Byrne, both with AgriLife Research; Dr. Weston Porter, Texas A&M University department of veterinary physiology and pharmacology; and then-graduate student Giuliana Noratto, who is now on the faculty at Washington State University.

In the western hemisphere, breast cancer is the most common malignant disease for women, he said. In the U.S. last year, the American Cancer Society estimated about 232,340 new cases of invasive breast cancer among women.

Most of the complications and high mortality associated with breast cancer are due to metastasis, Cisneros-Zevallos pointed out.

“The importance of our findings are very relevant, because it shows in vivo the effect that natural compounds, in this case the phenolic compounds in peach, have against breast cancer and metastasis. It gives opportunity to include in the diet an additional tool to prevent and fight this terrible disease that affects so many people,” he said.

The study was conducted using the peach variety Rich Lady. However, according to Cisneros-Zevallos, most peach fruit share similar polyphenolic compounds but might differ in content. The study also determined that the underlying mechanism by which peach polyphenols are inhibiting metastasis would be by targeting and modulating the gene expression of metalloproteinases.

“In general, peach fruit has chemical compounds that are responsible for killing cancer cells while not affecting normal cells as we reported previously, and now we are seeing that this mixture of compounds can inhibit metastasis,” said Cisneros-Zevallos. “We are enthusiastic about the idea that perhaps by consuming only two to three peaches a day we can obtain similar effects in humans. However, this will have to be the next step in the study for its confirmation.”

Cisneros-Zevallos continues testing these extracts and compounds in different types of cancer as well as in diabetes studies in vitro and in vivo to understand the molecular mechanisms involved.

Brain degeneration in Huntington’s disease caused by amino acid deficiency ( Cysteine )

In mice, dietary changes slow down progression of the disease

Working with genetically engineered mice, Johns Hopkins neuroscientists report they have identified what they believe is the cause of the vast disintegration of a part of the brain called the corpus striatum in rodents and people with Huntington’s disease: loss of the ability to make the amino acid cysteine. They also found that disease progression slowed in mice that were fed a diet rich in cysteine, which is found in foods such as wheat germ and whey protein.

Their results suggest further investigation into cysteine supplementation as a candidate therapeutic in people with the disease.

Up to 90 percent of the human corpus striatum, a brain structure that moderates mood, movement and cognition, degenerates in people with Huntington’s disease, a condition marked by widespread motor and intellectual disability. And while the genetic mutation underlying Huntington’s disease has long been known, the precise cause of that degeneration has remained a mystery.

In a report on their discovery in the advanced online publication of Nature on March 26, the Johns Hopkins researchers, led by Solomon Snyder, M.D., tracked the degenerative process to the absence of an enzyme, cystathionine gamma lyase, or CSE.

“Usually it’s very hard, if not impossible, to develop straightforward mechanisms that explain what’s going on in a disease. What’s even harder is even if you can find a mechanism that causes a tissue to rot, usually there’s nothing you can do about it,” says Snyder, a professor of neuroscience at the Johns Hopkins University School of Medicine. “In this case, there is.”

Huntington’s disease, an inherited disorder, does its damage because of abnormal DNA coding for the amino acid glutamine. Healthy individuals have some 15 to 20 DNA “repeats” in that part of their genetic code, while Huntington’s disease gene carriers have more than 36 — and often upward of 100. Children born to a parent carrier have a 50/50 chance of inheriting the disorder, and the greater the number of repeats, the earlier the age of onset of the incurable disorder.

Bindu Diana Paul, Ph.D., a molecular neuroscientist and faculty instructor in Snyder’s laboratory, was studying mice lacking CSE, which helps make the amino acid cysteine and hydrogen sulfide that moderate blood pressure and heart function. Paul, who had previous research experience with Huntington’s disease, says she was startled to observe that her mutant mice also behaved a lot like those with the disease.

When a normal mouse is dangled upside down from its tail, it will twist and turn and try to bite the offending hand, she explains. But her CSE-knockout mice stayed relatively still and clasped their paws together — the same behavior she’d observed in mice with the rodent equivalent of Huntington’s disease. “It looked like there was a neurological deficit,” Paul says. “But nobody had looked at CSE in the brain.”

Paul and Snyder began monitoring CSE in mouse and human brain tissues and found considerably less CSE in all diseased tissues. All people carry some normal huntingtin protein made by the Huntington’s disease gene, although the protein’s function remains elusive. But people with Huntington’s disease also carry mutant huntingtin proteins. Snyder and his team saw that the mutant proteins were attaching themselves to a crucial protein responsible for turning the CSE gene on or off, which ultimately led the diseased rodent and human brain tissues to be deprived of cysteine.

To see if loss of cysteine was directly responsible for the symptoms associated with Huntington’s disease, the Johns Hopkins team turned to readily available sources of the substance in everyday foods and fed mice a cysteine-rich diet.

The results, Paul says, were striking. When those mice were dangled from their tails, they resumed struggling, although with a bit less vigor than their healthy peers. They were able to grip an object with greater strength, and they took longer to fall off a balancing apparatus than CSE-knockout mice. Their life expectancies increased one to two weeks.

Snyder and Paul say they are cautiously optimistic about the results, noting that although they suggest a possible treatment for Huntington’s disease, it’s clear that a high cysteine diet merely slows rather than halts the progression of the disease. Moreover, the results in live mice may not occur in humans.

 

Beer marinade could reduce levels of potentially harmful substances in grilled meats

The smells of summer — the sweet fragrance of newly opened flowers, the scent of freshly cut grass and the aroma of meats cooking on the backyard grill — will soon be upon us. Now, researchers are reporting that the very same beer that many people enjoy at backyard barbeques could, when used as a marinade, help reduce the formation of potentially harmful substances in grilled meats. The study appears in ACS’ Journal of Agricultural and Food Chemistry.

I.M.P.L.V.O. Ferreira and colleagues explain that past studies have shown an association between consumption of grilled meats and a high incidence of colorectal cancer. Polycyclic aromatic hydrocarbons (PAHs) are substances that can form when meats are cooked at very high temperatures, like on a backyard grill. And high levels of PAHs, which are also in cigarette smoke and car exhaust, are associated with cancers in laboratory animals, although it’s uncertain if that’s true for people. Nevertheless, the European Union Commission Regulation has established the most suitable indicators for the occurrence and carcinogenic potency of PAHs in food and attributed maximum levels for these compounds in foods. Beer, wine or tea marinades can reduce the levels of some potential carcinogens in cooked meat, but little was known about how different beer marinades affect PAH levels, until now.

The researchers grilled samples of pork marinated for four hours in Pilsner beer, non-alcoholic Pilsner beer or a black beer ale, to well-done on a charcoal grill. Black beer had the strongest effect, reducing the levels of eight major PAHs by more than half compared with unmarinated pork. “Thus, the intake of beer marinated meat can be a suitable mitigation strategy,” say the researchers.

More severe heart disease found in patients with vitamin D deficiency

Lower levels of vitamin D predict extent of coronary artery disease

WASHINGTON (March 27, 2014) — Vitamin D deficiency is an independent risk factor for heart disease with lower levels of vitamin D being associated with a higher presence and severity of coronary artery disease, according to research to be presented at the American College of Cardiology’s 63rd Annual Scientific Session.

A growing body of research shows that vitamin D may be beneficial in preventing heart disease. Several recent studies also support the idea that low levels of vitamin D are linked to an increased risk of heart disease; however, it is still not clear whether adding vitamin D supplements may help reduce that risk.

In the largest study of its kind to evaluate the relationship between vitamin D levels and coronary artery disease, vitamin D deficiency (20ng/mL) was observed in 70.4 percent of patients undergoing coronary angiography – an imaging test used to see how blood flows through the arteries in the heart. Vitamin D deficiency was associated with higher prevalence of coronary artery disease, with a 32 percent higher occurrence in patients with the lowest vitamin D levels and a near 20 percent higher frequency of severe disease affecting multiple vessels. A progressive increase in heart disease was found according to the severity of vitamin D deficiency. Patients with values lower than 10 mg/dl had a near two-fold increased rate of coronary atherosclerosis as compared with those showing normal levels.

Researchers evaluated vitamin D levels in 1,484 patients. Vitamin D deficiency was defined as levels lower than 20ng/mL, and severe vitamin D deficiency was defined as levels under 10ng/mL. Patients were considered to have coronary artery disease if they had a diameter reduction of greater than 50 percent in at least one coronary artery. The extent and severity of heart disease were measured by quantitative coronary angiography – a procedure that determines the degree of blockage in arteries.

“Present results suggest vitamin D deficiency to be the cause rather than the consequence of atherosclerosis,” said Monica Verdoia, M.D., specializing cardiologist at the Department of Cardiology, Ospedale Maggiore della Carità, Eastern Piedmont University in Novara, Italy, and investigator on the study on behalf of the Novara Atherosclerosis study group by Prof. Giuseppe De Luca. “Although evidence of benefits with vitamin D supplementation in cardiovascular outcomes are still lacking, strategies to raise endogenous vitamin D should probably be advised in the prevention of cardiovascular disease.”

A diet rich in vitamin D and moderate exercise outdoors should be advised in both patients with and without cardiovascular disease, Verdoia said. Vitamin D acts as a regulator on the function of the immune system as well as inflammatory processes that contribute to risk factors for heart disease, she said.

Verdoia said the importance of the study is to provide deeper insight into stratification tools for assessing the risk of coronary artery disease in a real world population, where vitamin D deficiency has a dramatic prevalence. She stresses the need to make funding a priority in the research on vitamin D in cardiovascular prevention. The research team plans to proceed with clinical trials evaluating the treatment of vitamin D deficiency and to investigate the mechanisms by which vitamin D can influence the development of atherosclerosis.

Researchers estimate that more than half of U.S. adults are vitamin D deficient, with the highest rates among African Americans and Hispanics. Vitamin D is being studied for its possible connection to several diseases and health problems, including diabetes, high blood pressure, multiple sclerosis, autoimmune conditions, bone disorders and some types of cancer.

A limitation of the study is that researchers did not evaluate the long-term outcomes for study patients, so it is unknown whether those with lower vitamin D levels experienced a higher rate of recurrent events or a quicker progression of the coronary disease, although other studies have suggested this is the case.

One size does not fit all: Dietary guidelines for choline may be insufficient

New research in the FASEB Journal suggests that genetic variations influence the risk of developing symptoms of choline deficiency and determine the propensity of liver or muscle damage outcomes

What is now considered to be the “right” amount of the essential nutrient, choline, might actually be “wrong,” depending on who you are. That’s because scientists have found that the “right” amount of choline needed by an individual is influenced by a wide range of factors, including gender, life stage, race and ethnicity of the individual. This means that using the current one-size-fits-all approach to determining a person’s vitamin and mineral needs may leave them in less than optimal health. Choline is an essential nutrient used by the body to construct cell membranes and is necessary for the health of vital organs and muscles. This finding was published online in The FASEB Journal.

“Our study shows that gender, life stage and genetic makeup influence the requirement for choline in humans,” said Kerry-Ann da Costa Ph.D., a researcher involved in the work from the Department of Nutrition at the University of North Carolina, Chapel Hill. “We hope that it will focus attention on setting the dietary recommendations at a level that is high enough to meet the needs of those with the greatest requirements for choline.”

To make this discovery, da Costa and colleagues analyzed healthy men and women who were fed a baseline diet containing 550 mg choline/day (the adequate intake level set by the Institute of Medicine) for 10 days. Then they were put on a low choline diet (50 mg choline/day) for up to 42 days, and monitored for increased liver fat and changes in liver and muscle function. If they developed clinical symptoms, choline was returned to their diet until these symptoms resolved. Subjects were categorized by symptoms – liver, muscle or none. DNA isolated from their blood was examined for 200 single nucleotide polymorphisms or SNPs in 10 choline-related genes to see which ones were associated with liver or muscle damage compared to the people with no symptoms. Several SNPs were identified in women that alter their risk when they are on a low choline diet. Other SNPs in the choline transporter gene SLC44A1 and choline kinase beta gene (CHKB) were identified in the people with muscle damage compared to the rest of the study participants. Researchers then looked at these SNPs in European-, Mexican-, Asian- and African-Americans and in individuals of African descent, and found that the distribution was often quite different between the groups.

“Getting the right amount of choline is important, and also important is this study which shows that each person has unique nutritional needs. Today’s dietary guidelines are approximations at best, and one size does not fit all,” said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “As we move toward an age of personalized medicine, studies like this should make it possible for health care professionals to judge how much of each nutrient your particular body needs.”

FASEB is composed of 26 societies with more than 115,000 members, making it the largest coalition of biomedical research associations in the United States. Our mission is to advance health and welfare by promoting progress and education in biological and biomedical sciences through service to our member societies and collaborative advocacy.

Details: Kerry-Ann da Costa, Karen D. Corbin, Mihai D. Niculescu, Joseph A. Galanko, and Steven H. Zeisel. Identification of new genetic polymorphisms that alter the dietary requirement for choline and vary in their distribution across ethnic and racial groups. FASEB J. doi:10.1096/fj.14-249557 ; http://www.fasebj.org/content/early/2014/03/25/fj.14-249557.abstract

Eating fruits and vegetables linked to healthier arteries later in life

Study shows lower prevalence of plaque build-up in women, but not men

WASHINGTON (March 28, 2014) — Women who ate a diet high in fresh fruits and vegetables as young adults were much less likely to have plaque build-up in their arteries 20 years later compared with those who consumed lower amounts of these foods, according to research to be presented at the American College of Cardiology’s 63rd Annual Scientific Session. This new finding reinforces the importance of developing healthy eating habits early in life.

Previous studies have found that middle-aged adults whose diet consists of a high proportion of fruits and vegetables are less likely to have a heart attack or stroke, but the relationship between fruit and vegetable consumption during young adulthood and heart disease later in life was less clear. To study this concept, researchers evaluated the association between dietary intake of fruits and vegetables in young adults and the presence of coronary artery calcification (CAC) 20 years later. CAC scores, which were obtained using a CT scan, provide a direct estimate of the amount of plaque in the coronary arteries.

“It’s an important question because lifestyle behaviors, such as a heart healthy diet, are the foundation of cardiovascular prevention and we need to know what dietary components are most important,” said Michael D. Miedema, M.D., M.P.H., a cardiologist at the Minneapolis Heart Institute, and the lead investigator of the study.

Specifically, women who reported consuming the most fruits and vegetables (eight to nine servings a day for a 2,000-calorie diet) in their 20s were 40 percent less likely to have calcified plaque in their arteries in their 40s compared with those who ate the least amount (three to four servings a day) during the same time period. This association persisted even after researchers accounted for other lifestyle behaviors, as well as for their current-day diets, further demonstrating the role dietary patterns at younger ages may play.

“These findings confirm the concept that plaque development is a lifelong process, and that process can be slowed down with a healthy diet at a young age,” Miedema said. “This is often when dietary habits are established, so there is value in knowing how the choices we make in early life have lifelong benefits.”

Surprisingly, the same benefit did not hold true for men, which warrants further investigation.

“Several other studies have also suggested that a diet high in fruits and vegetables is less protective in men, but we do not have a good biological reason for this lack of association,” Miedema said, adding that the study had less power to evaluate men (62.7 percent were female vs. 37.3 percent male).

The study included 2,508 participants from the ongoing government-sponsored Coronary Artery Risk Development in Young Adults (CARDIA) study, which is evaluating how heart disease develops throughout adulthood. CARDIA began in the mid-1980s with a group of men and women 18-30 years of age and has collected extensive data on medical, socioeconomic, psychosocial and behavioral characteristics.

At the start of CARDIA (1985-1986), women and men were asked about their consumption of different fruits and vegetables and the number of servings they had eaten in the past month using a semi-quantitative interview food-frequency questionnaire. Researchers then calculated the average number of servings of fruits and vegetables per day and adjusted them to a 2,000-calorie diet. People were divided into three groups based on self-reported fruit and vegetable intake: high, moderate and low. CAC was measured at year 20 (2005-2006) using electron-beam computed tomography. The average age at baseline and the 20-year follow-up was 25 and 45 years, respectively.

“CAC scoring is currently the best predictor we have for future heart attacks,” Miedema said. Calcium build-up in the walls of the coronary arteries is an early sign of heart disease, and the presence of CAC substantially raises an individual’s risk for a future heart attack.

In their analysis, researchers controlled for smoking, exercise, consumption of red meat, sugar-sweetened beverages and other dietary and cardiovascular risk factors that correlate with atherosclerosis. Participants with extreme high or low caloric intake/day or those missing CAC scores were excluded from the analysis.

The current findings are in line with the 2011 U.S. Department of Agriculture Dietary Guidelines that advise Americans to fill half of their plates with colorful fruits and vegetables at each meal or snack. Based on these recommendations, adults who consume a 2,000-calorie a day diet should be consuming 2.5 cups of vegetables and two cups of fruit a day – a big jump from what the average American usually gets from their diet, according to government figures.

Fruits and vegetables are packed with vitamins, minerals, fiber, antioxidants and other things that are known to promote good health. Plant-based diets in general have also been linked to greater longevity, less cancer, lower cholesterol, lower blood pressure and healthier body weight.

Miedema emphasized that more studies are needed to further define the relationship between fruits, vegetables and cardiovascular disease in men and women, in addition to determining the best ways to increase compliance with a diet high in fruits and vegetables in the U.S. population.

 

UNC researchers show cancer chemotherapy accelerates ‘molecular aging’

Physicians have long suspected that chemotherapy can accelerate the aging process in patients treated for cancer. Using a test developed at UNC Lineberger Comprehensive Cancer Center to determine molecular aging, UNC oncologists have directly measured the impact of anti-cancer chemotherapy drugs on biological aging.

Researchers measured the level of p16, a protein that causes cellular aging, in the blood of 33 women over the age of 50 who had undergone chemotherapy for curable breast cancer. Samples were taken for analysis of molecular age from patients before chemotherapy, immediately following chemotherapy and a year after therapy finished. The analysis showed that curative chemotherapy also caused an increase in a patient’s molecular age that on average was equivalent to 15 years of normal aging. The same was true in a separate group of 176 breast cancer survivors who had received chemotherapy on average three and a half years prior.

The study, headed by Hanna Sanoff, MD, MPH, assistant professor with the UNC School of Medicine and member of UNC Lineberger, is published in this week’s Journal of the National Cancer Institute. Dr. Sanoff said that the results indicate that the p16 test holds promise as a means of evaluating how chemotherapy will affect a patient’s long-term health and survival and as a predictive biomarker for the long-term toxicity of chemotherapy.

“Our theory is that if you have an advanced molecular age to begin with, it will be harder for you to tolerate chemotherapy,” said Dr. Sanoff. “We believe a high level of p16 before treatment could mean that a patient will have a harder time making new blood cells after each chemotherapy treatment, and therefore be at greater risk for anemia and infection during chemotherapy.”

The key role of p16 in human aging has been established over the last decade in the lab of UNC Lineberger Director Dr. Norman Sharpless. Research conducted in Sharpless’ lab showed in 2004 that the levels of p16 increase exponentially with aging, and developed the p16 blood test for human use in 2009.

The next direction for this research, ongoing under the leadership of Dr. Hyman Muss, director of UNC Lineberger’s Geriatric Oncology Program, involves determining if markers of molecular age predict patients’ physical function and outcome in a number of clinical settings.

“While these findings are highly provocative, we have much more to study and will have to verify in future trials how these changes in molecular aging affect long term survival,” said Dr. Muss. “Adjuvant chemotherapy has dramatically improved breast cancer survival and pending further data, the results of our study should not effect adjuvant chemotherapy decisions.”

The p16 test seems particularly well-suited as an aging marker for this purpose as it plays a causal role in biological aging, is strongly correlated with chronological aging, and increases exponentially in response to pro-aging stimuli. Dr. Sanoff said she believes the test has promise as the basis of a clinical tool allowing physicians to evaluate the degree to which a given treatment accelerates biological and physical aging.

 

 

 

Too many diet drinks may spell heart trouble for older women

Largest study of its kind looks at diet drinks and cardiovascular outcomes, mortality

It appears healthy postmenopausal women who drink two or more diet drinks a day may be more likely to have a heart attack, stroke or other cardiovascular problems, according to research to be presented at the American College of Cardiology’s 63rd Annual Scientific Session.

In fact, compared to women who never or only rarely consume diet drinks, those who consumed two or more a day were 30 percent more likely to suffer a cardiovascular event and 50 percent more likely to die from related disease. Researchers analyzed diet drink intake and cardiovascular risk factors from 59,614 participants in the Women’s Health Initiative Observational Study, making this the largest study to look at the relationship between diet drink consumption, cardiac events and death.

“Our findings are in line with and extend data from previous studies showing an association between diet drinks and metabolic syndrome,” said Ankur Vyas, M.D., fellow, Cardiovascular Diseases, University of Iowa Hospitals and Clinics, and the lead investigator of the study. “We were interested in this research because there was a relative lack of data about diet drinks and cardiovascular outcomes and mortality.”

Information on women’s consumption of diet drinks was obtained through a questionnaire that asked them to report their diet drink consumption habits over the previous three months. This information was assessed at follow-up year three of the Women’s Health Initiative Observational Study. Each drink was defined as the equivalent of a 12-ounce beverage and included both diet sodas and diet fruit drinks. For the purposes of the analysis, researchers divided the women into four consumption groups: two or more diet drinks a day, five to seven diet drinks per week, one to four diet drinks per week, and zero to three diet drinks per month.

After an average follow-up of 8.7 years, the primary outcome – a composite of incident coronary heart disease, congestive heart failure, heart attack, coronary revascularization procedure, ischemic stroke, peripheral arterial disease and cardiovascular death – occurred in 8.5 percent of the women consuming two or more diet drinks a day compared to 6.9 percent in the five-to-seven diet drinks per week group; 6.8 percent in the one-to-four drinks per week group; and 7.2 percent in the zero-to-three per month group.

The association persisted even after researchers adjusted the data to account for demographic characteristics and other cardiovascular risk factors and comorbidities, including body mass index, smoking, hormone therapy use, physical activity, energy intake, salt intake, diabetes, hypertension, high cholesterol and sugar-sweetened beverage intake. Women who consumed two or more diet drinks a day were younger, more likely to be smokers, and had a higher prevalence of diabetes, hypertension and higher body mass index.

But Vyas says the association between diet drinks and cardiovascular problems raises more questions than it answers, and should stimulate further research.

“We only found an association, so we can’t say that diet drinks cause these problems,” Vyas said, adding that there may be other factors about people who drink more diet drinks that could explain the connection.

“It’s too soon to tell people to change their behavior based on this study; however, based on these and other findings we have a responsibility to do more research to see what is going on and further define the relationship, if one truly exists,” he adds. “This could have major public health implications.”

About one in five people in the U.S. consume diet drinks on a given day, according to data from the National Health and Nutrition Examination Survey (2009-2010). But Vyas cautions that this particular study only applies to postmenopausal women. The average age in the study was 62.8. To be included in this analysis, women had to have no history of cardiovascular disease and be alive 60 or more days from time of data collection.

Previous studies have found artificially sweetened drinks to be associated with weight gain in adults and teens, and seem to increase the risk of metabolic syndrome, which makes both diabetes and heart disease more likely.

Vyas says future research could include clinical studies, animal models and even molecular and pharmacologic analyses to begin to explain what, if any, direct role diet drinks play in heart health.

Can antibiotics cause autoimmunity?

Antibiotics being explored for the treatment of cystic fibrosis and muscular dystrophy have the potential to trigger autoimmune disease

(PHILADELPHIA) — The code for every gene includes a message at the end of it that signals the translation machinery to stop. Some diseases, such as cystic fibrosis and Duchenne muscular dystrophy, can result from mutations that insert this stop signal into the middle of an essential gene, causing the resulting protein to be truncated. Some antibiotics cause the cell’s translation machinery to ignore the stop codons and are therefore being explored as a potential therapy for these diseases. But new research reported online in Proceedings of the National Academy of Sciences (the week of March 31st) shows that this approach could come with the price of triggering autoimmune disease.

“It’s worth thinking about this as a potential mechanism for autoimmunity,” says co-lead investigator, Laurence Eisenlohr, Ph.D., a professor in the department of Microbiology and Immunology at Thomas Jefferson University.

Autoimmune diseases such as Crohn’s disease, eczema, or lupus are caused by an immune system that attacks normal components of various tissues of the body. The immune system attacks these normal tissues just as it would attack tissue infected by a bacteria or virus. What causes the immune system to malfunction in some people but not others, however, has been a puzzle. “Often, the trigger happens years before the disease has been diagnosed,” says Dr. Eisenlohr.

The researchers looked at a class of antibiotics that includes gentamicin because these antibiotics have the unique property of inducing cells to read through stop codons in the genetic code – producing a longer protein product. This mechanism can help save the translation of mutated genes whose processing is interrupted by aberrant stop codons, such as in cystic fibrosis. However, when cellular machinery reads through normal stop codons, it could create abnormally elongated proteins in the cell. Pieces of these abnormal proteins may be presented to the immune system as a part of normal protein processing, where they could be detected by the immune system. At least, that’s the theory.

To test this theory, Eisenlohr’s team, in collaboration with a translation biology group at the University of Utah led by Michael Howard, Ph.D., used a gene that they knew would get presented to the immune system and added a stop codon in the middle of it. They then inserted this gene into a mammalian cell line. Because the stop codon truncates the gene, normal cells did not produce the protein. However, when the researchers treated the cells with gentamicin, they began to detect the protein on the surface of cells.

While a very low number of these proteins were produced – too little to detect by normal biochemical tests – the T cells of the immune system are sensitive enough to pick up these miniscule amounts. Indeed, the group showed that the immune cells could detect the protein produced by gentamicin-treated cells, even at low quantities.

To test whether this process was active even in normal cells that weren’t expressing an experimental gene, first author Elliot Goodenough exposed the HeLa human cell line to gentamicin and then searched for novel peptides presented on the surface of the cells. He identified 17 peptides that hadn’t been characterized before in cells treated with gentamicin and showed that the peptides were presentable to the immune system. “The results suggest that gentamicin can cause cells to display novel protein fragments to the immune system,” says Goodenough. In other words, “what may be garbage biologically may be important immunologically,” says Eisenlohr.

However, presenting an antigen to the immune system does not guarantee that it will activate the kind of immune response that initiates autoimmunity. But because gentamicin is usually used to treat infections, “all of the right conditions are in place to potentially initiate autoimmunity,” says Eisenlohr. The inflammation associated with bacterial diseases gives a signal to immune cells that the peptides they encounter are dangerous. So even as gentamicin fights the bacteria causing the infection, it also causes normal cells to produce abnormal proteins that are presented to the immune system and have a potential of initiating an autoimmune reaction.

“A number of autoimmune diseases are thought to be triggered by infections,” says Eisenlohr. “The results of this study suggest that certain antibiotics used to treat those infections may also contribute to that trigger.”

The next steps, says Eisenlohr, could be to look at population data to see whether use of gentamicin correlates with higher rates of autoimmune diseases, as well as testing whether the peptides generated during gentamicin treatment actually do cause autoimmunity in a mouse model of the disease.

 

Breast milk and diet up to 2 years old: a means of preventing the risk of child obesity

 

Many studies have focused on the influence of breast-feeding on child health. From analysis of data from the ELANCE cohort, Marie Françoise Rolland-Cachera, former researcher at Inserm and her co-workers in the Nutritional Epidemiology Research Team (EREN)[1] have shown that breast-feeding has a protective effect on the risk of obesity at 20 years of age. Researchers also emphasise that nutritional intake at the age of 2 years are critical in providing this beneficial effect. The results of the study are published in The Journal of Pediatrics

Recent studies have focused on the influence of breast-feeding on the risk of the child developing obesity: results showed beneficial but still inconclusive trends. They adjusted their results by considering various factors such as social categories, the weight of parents, age of diversification, etc. but until now no study had made adjustment for nutritional intakes subsequent to breast-feeding. It has now been shown that nutrition during the first two years of life had long-term consequences on health that can persist into adulthood.

 

Researchers therefore studied relationships between breast-feeding and the risk of excess weight in adulthood by considering diet at 10 months and 2 years for children included in the ELANCE cohort.

The ELANCE Cohort started with children in good health, born in 1984 and 1985, recruited in Child Health Assessment Centres. Information on breast-feeding was gathered and nutritional intakes was assessed at ages 10 months and 2 years, then every two years up to the age of 20. At 20 years, several measurements were taken, including height, weight and body composition (measurements of lean mass and fat mass determined by impedancemetry).

The results show that the beneficial effect of breast-feeding is clearly seen when nutritional intake up to the age of 2 is considered and is significantly linked to a reduction in body fat at 20 years old. Furthermore, in the statistical model, higher fat intake at 2 years are linked to a reduction in fat mass at 20 years.

“Our study has therefore shown, for the 1st time, that if we take account of diet after the period of breast-feeding, the protective role of breast milk over the risk of obesity is clearly apparent,” explains Marie Françoise Rolland-Cachera, former Inserm researcher.

 

The diet of young children is often characterised by high protein intake and low fat intake; breast milk is rich in fat and contains a small proportion of protein. According to official recommendations, fats should not be restricted in young children in order to meet their high energy requirements for growth and rapid development of their nervous system. In particular, low-calorie dairy products with low fat content and a high proportion of protein are not indicated before the age of 2-3 years. Restricted fats may programme the child’s metabolism to deal with this deficit, but this adaptation will make it more likely become overweight when the fat intake increases later on.

“The beneficial effect of breast milk may be masked by a low-fat diet following breast-feeding, while a diet following official recommendations (no restriction in fats before the age of 2-3 years) allows its beneficial effect to appear” emphasises Sandrine Péneau, co-author of this work.

Researchers agree about the benefit of breast-feeding reducing the risk of future obesity and highlight the importance of a diet following official recommendations in relation to young children. A poorly-balanced diet after breast-feeding can compromise the benefit provided by breast milk and explain the controversies over its protective role against the risk of obesity.

Adult Tonsillectomy Complications and Health Care Expenses

 

New Findings Contribute to Ongoing Discussion
ALEXANDRIA, VA — A study released today of 36,210 adult tonsillectomy patients finds that 20 percent will have a complication, offering valuable new insights to a decades long discussion. The study, featured in the April 2014 issue of Otolaryngology—Head and Neck Surgery, examines the prevalence of complications in adult tonsillectomies and the impact on health care expenditures.

“Researchers have been examining variation in tonsillectomy for years,” explained corresponding author, Dennis Scanlon, PhD. “Yet most research has been documented in pediatric populations. Much less is known about the safety and risks to adult patients that undergo the procedure.”

The study is the first of its kind to examine a large adult population, across institutions and provider practices. Data for the study came from MarketScan®, a large insurance database of patients with employer-sponsored insurance who had an outpatient tonsillectomy between 2002 and 2007. Previous studies have focused on small numbers of patients within particular institutions and have not considered a wider spectrum of complications beyond post-tonsillectomy hemorrhage. The findings suggest that of the 20 percent who will have a complication, 10 percent will visit an emergency room, and approximately 1.5 percent will be admitted to a hospital within 14 days of the procedure. Six percent were treated for postoperative hemorrhage, 2 percent for dehydration, and 11 percent for ear, nose or throat pain within 14 days of surgery. These estimated complication rates are significantly higher than those reported in prior studies. The study results highlight the challenges patients face when making informed decisions about medical and surgical treatments, as well as the excess costs and harm incurred due to complications. On average, the amount paid for a tonsillectomy without complication was $3,832 whereas tonsillectomy with hemorrhage resulted in an average expenditure of $6,388.   “Patients expect to compare the risks and benefits of treatment options, but as our study shows, credible patient centered information is often lacking, even for a common procedure that has been in practice for many, many years. The availability of important risk or benefit information should be expedited and providers need to be trained to engage patients in how to use this information to make informed choices,” said Dr. Scanlon.

Key chocolate ingredients could help prevent obesity, diabetes

Improved thinking. Decreased appetite. Lowered blood pressure. The potential health benefits of dark chocolate keep piling up, and scientists are now homing in on what ingredients in chocolate might help prevent obesity, as well as type-2 diabetes. They found that one particular type of antioxidant in cocoa prevented laboratory mice from gaining excess weight and lowered their blood sugar levels. The report appears in ACS’ Journal of Agricultural & Food Chemistry.

Andrew P. Neilson and colleagues explain that cocoa, the basic ingredient of chocolate, is one of the most flavanol-rich foods around. That’s good for chocolate lovers because previous research has shown that flavanols in other foods such as grapes and tea can help fight weight gain and type-2 diabetes. But not all flavanols, which are a type of antioxidant, are created equal. Cocoa has several different kinds of these compounds, so Neilson’s team decided to tease them apart and test each individually for health benefits.

The scientists fed groups of mice different diets, including high-fat and low-fat diets, and high-fat diets supplemented with different kinds of flavanols. They found that adding one particular set of these compounds, known as oligomeric procyanidins (PCs), to the food made the biggest difference in keeping the mice’s weight down if they were on high-fat diets. They also improved glucose tolerance, which could potentially help prevent type-2 diabetes. “Oligomeric PCs appear to possess the greatest antiobesity and antidiabetic bioactivities of the flavanols in cocoa, particularly at the low doses employed for the present study,” the researchers state.

Coffee consumption reduces mortality risk from liver cirrhosis

Drinking tea, fruit juice or soft drinks not found to affect risk of cirrhosis death

New research reveals that consuming two or more cups of coffee each day reduces the risk of death from liver cirrhosis by 66%, specifically cirrhosis caused by non-viral hepatitis. Findings in Hepatology, a journal published by Wiley on behalf of the American Association for the Study of Liver Diseases, show that tea, fruit juice, and soft drink consumption are not linked to cirrhosis mortality risk. As with previous studies heavy alcohol use was found to increase risk of death from cirrhosis.

A 2004 report from The World Health Organization (WHO) estimates that each year 1.3% of total death worldwide is caused by liver cirrhosis. Previous research shows that 29 million Europeans have chronic liver disease, with 17,000 deaths annually attributed to cirrhosis. Further WHO reports state that liver cirrhosis is the 11th leading cause of death in the U.S.

“Prior evidence suggests that coffee may reduce liver damage in patients with chronic liver disease,” said lead researcher, Dr. Woon-Puay Koh with Duke-NUS Graduate Medical School Singapore and the National University of Singapore. “Our study examined the effects of consuming coffee, alcohol, black tea, green tea, and soft drinks on risk of mortality from cirrhosis.”

This prospective population-based study, known as The Singapore Chinese Health Study, recruited 63,275 Chinese subjects between the ages of 45 and 74 living in Singapore. Participants provided information on diet, lifestyle choices, and medical history during in-person interviews conducted between 1993 and 1998. Patients were followed for an average of nearly 15 years, during which time there were 14,928 deaths (24%); 114 of them died from liver cirrhosis. The mean age of death was 67 years.

Findings indicate that those who drank at least 20 g of ethanol daily had a greater risk of cirrhosis mortality compared to non-drinker. In contrast, coffee intake was associated with a lower risk of death from cirrhosis, specifically for non-viral hepatitis related cirrhosis. Non-alcoholic fatty liver disease (NAFLD), a chronic liver disease related to the metabolic syndrome and more sedentary affluent lifestyle, likely predominates among the non-viral hepatitis related cirrhosis group. In fact, subjects who drank two or more cups per day had a 66% reduction in mortality risk, compared to non-daily coffee drinkers. However, coffee intake was not associated with viral hepatitis B related cirrhosis mortality.

“Our study is the first to demonstrate a difference between the effects of coffee on non-viral and viral hepatitis related cirrhosis mortality,” concludes Dr. Koh. “This finding resolves the seemingly conflicting results on the effect of coffee in Western and Asian-based studies of death from liver cirrhosis. Our finding suggests that while the benefit of coffee may be less apparent in the Asian population where chronic viral hepatitis B predominates currently, this is expected to change as the incidence of non-viral hepatitis related cirrhosis is expected to increase in these regions, accompanying the increasing affluence and westernizing lifestyles amongst their younger populations.”

Chowing down on watermelon could lower blood pressure

 

03/25/2014 9:26 am

 

Nutrition, Food and Exercise Sciences Associate Professor Arturo Figueroa.

Be sure to pick up a watermelon — or two — at your local grocery store.

It could save your life.

 

A new study by Florida State University Associate Professor Arturo Figueroa, published in the American Journal of Hypertension, found that watermelon could significantly reduce blood pressure in overweight individuals both at rest and while under stress.

“The pressure on the aorta and on the heart decreased after consuming watermelon extract,” Figueroa said.

The study started with a simple concept. More people die of heart attacks in cold weather because the stress of the cold temperatures causes blood pressure to increase and the heart has to work harder to pump blood into the aorta. That often leads to less blood flow to the heart.

Thus, people with obesity and high blood pressure face a higher risk for stroke or heart attack when exposed to the cold either during the winter or in rooms with low temperatures.

So, what might help their hearts?

It turned out that watermelon may be part of the answer.

Figueroa’s 12-week study focused on 13 middle-aged, obese men and women who also suffered from high blood pressure. To simulate cold weather conditions, one hand of the subject was dipped into 39 degree water (or 4 degrees Celsius) while Figueroa’s team took their blood pressure and other vital measurements.

Meanwhile, the group was divided into two. For the first six weeks, one group was given four grams of the amino acid L-citrulline and two grams of L-arginine per day, both from watermelon extract. The other group was given a placebo for 6 weeks.

Then, they switched for the second six weeks.

Participants also had to refrain from taking any medication for blood pressure or making any significant changes in their lifestyle, particularly related to diet and exercise, during the study.

The results showed that consuming watermelon had a positive impact on aortic blood pressure and other vascular parameters.

Notably, study participants showed improvements in blood pressure and cardiac stress while both at rest and while they were exposed to the cold water.

“That means less overload to the heart, so the heart is going to work easily during a stressful situation such as cold exposure,” Figueroa said.

Figueroa has conducted multiple studies on the benefits of watermelon. In the past, he examined how it impacts post-menopausal women’s arterial function and the blood pressure readings of adults with pre-hypertension.

In addition to being published in the American Journal of Hypertension, the study was also published in the US National Library of Medicine National Institutes of Health and was one of the “top new hypertensive articles” in MDLinx.

Higher total folate intake may be associated with lower risk of exfoliation glaucoma

Results published in JAMA Ophthalmology

BOSTON (April 4, 2014) — Exfoliation glaucoma (EG), caused by exfoliation syndrome, a condition in which white clumps of fibrillar material form in the eye, is the most common cause of secondary open-angle glaucoma and a leading cause of blindness and visual impairment. Effective strategies for preventing this disease are lacking.

Elevated homocysteine, which may enhance exfoliation material formation, is one possible risk factor that has received significant research attention. Research studies demonstrate that high intake of vitamin B6, vitamin B12 and folate is associated with lower homocysteine levels. A prospective study from Massachusetts Eye and Ear, Brigham and Women’s Hospital (BWH) / Harvard Medical School (HMS), and Harvard School of Public Health (HSPH) set out to evaluate the association between the intake of these vitamins and EG.

The researchers designed a prospective cohort study using more than 20 years of follow-up data from the Nurses’ Health Study (all female registered nurses) and the Health Professionals Follow-up Study (all male health professionals) from June 1, 1980 to May 31, 2010 (Nurses’ Health Study) and Jan. 1, 1986 to Dec. 31, 2010 (Health Professionals Follow-up Study). They observed that higher total folate intake was associated with a lower risk for EG/suspected exfoliation glaucoma (SEG), supporting a possible causal role of homocysteine in EG/SEG. Their results are published online in the April 3, 2014 issue of JAMA Ophthalmology.

“We included a subset of 78,980 women and 41,221 men who were 40 years or older, free of glaucoma, had completed dietary questionnaires, and reported an eye examination during follow-up,” said lead author Jae H. Kang, Sc.D., Channing Division of Network Medicine, Department of Medicine, BWH/HMS. “Incident cases of EG/SEG, totaling 339 were first identified with the questionnaires and were subsequently confirmed with medical records. Multivariable relative risks for EG/SEG were calculated in each cohort and then pooled with meta-analysis.”

The results showed that vitamin B6 and B12 intake was not associated with EG/SEG risk in pooled analyses (P= .52 and P= .99 for linear trend, respectively). However, there was a trend of a reduced risk of EG/SEG with higher total folate intake, with relations being stronger for higher folate intake from supplements than from diet alone.

“Our conclusions are that higher folate intake is associated with a lower risk for EG/SEG, supporting a possible causal role of homocysteine in EG/SEG,” said senior author Louis Pasquale, M.D., Glaucoma Service Director, Mass. Eye and Ear. “More work needs to be done but these are critical insights that may give us a better understanding of how EG progresses, which helps to bring us closer to developing interventions or treatments that prevent this blinding disease.”