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New Risk Stratification for Breast Cancer

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

MD Anderson Researchers Develop New Breast Cancer Staging System

https://www.genomeweb.com/cancer/md-anderson-researchers-develop-new-breast-cancer-staging-system

NEW YORK (GenomeWeb) – Researchers at the University of Texas MD Anderson Cancer Center have developed a new breast cancer staging system that incorporates tumor biology as a critical prognostic indicator for women who undergo neoadjuvant therapy.

Published this week in JAMA Oncology, the Neo-Bioscore staging system incorporates HER2/ERBB2 status, which allows for more precise prognostic stratification of all breast cancer subtypes.

To date, breast cancer patient staging involved considering the size of the primary tumor, metastasis, or disease in the lymph nodes at the time of presentation as the primary factors.However, this fails to take into account the biology of the tumor, which has shown to be critically important, Elizabeth Mittendorf, associate professor of Breast Surgical Oncology at MD Anderson and corresponding author on the study, said in a statement.

The new system builds on the development of an earlier breast cancer staging system developed by MD Anderson, CPS+EG, that incorporates preclinical stage, estrogen receptor status, grade, and post-treatment pathologic stage. While it was an improvement from previous methods, it is no longer a sufficient staging system because it predates the routine use of trastuzumab in the neoadjuvant setting and therefore had a limited ability to provide prognostic information for HER2/ERBB2-positive patients, Mittendorf said.

To develop the staging system, the researchers conducted a retrospective study that evaluated 2,377 MD Anderson breast cancer patients who all had non-metastatic invasive breast cancer and were treated with neoadjuvant chemotherapy.

Each patient’s clinicopathologic data were recorded, including age, clinical and pathological stage, ER status, HER2/ERBB2 status, and nuclear grade. Patients’ ER status was recorded as a percentage of cells staining positive under immunohistochemical analysis. Their ERBB2 status was defined as positive at a reading of 3+ on immunohistochemical analysis or when gene amplification was shown on fluorescence in situ hybridization.

All patients received an anthracycline and/or taxane-based neoadjuvant chemotherapy regimen. Patients with HER2/ERBB2-positive disease routinely completed one year of trastuzumab therapy. After completing chemotherapy, patients underwent either breast-conserving therapy or mastectomy with axillary evaluation with or without post-mastectomy irradiation.

Patients’ CPS+EG score was determined according to the previously published staging system and was calculated twice (once using 1 percent or higher as the cutoff for ER positivity and again using 10 percent or higher as the cutoff).

Their disease-specific survival (DSS) was also calculated using multiple staging systems: AJCC clinical stage, AJCC pathologic stage, CPS+EG (1 percent cutoff), and CPS+EG (10 percent cutoff). Within each staging system, DSS among subgroups was compared using the log-rank test.

After the researchers determined a CPS+EG score for each patient, they added the patient’s respective HER2/ERBB2 status to the model. They then constructed the novel staging system by adding a point to the CPS+EG score for HER2-negative tumors. In the study cohort, 591 patients were HER2/ERBB2 positive.

The researchers found that in addition to validating previous findings that CPS+EG score improved prognostication of patients, the Neo-Bioscore created a more refined stratification in approximately 75 percent of the study cohort. This shift reflects the number of HER2/ERBB2-negative tumors in the study and demonstrated that adding HER2/ERBB2 standards created a highly significant improvement.

“With this tool, I can give my patients the precise information they are looking for: a more refined prognosis. Also, with this data, we will know which patients are in greatest need of additional therapy,” Mittendorf said. “Hopefully these findings will result in more informed conversations between doctor and patient.”

 

The Neo-Bioscore Update for Staging Breast Cancer Treated With Neoadjuvant ChemotherapyIncorporation of Prognostic Biologic Factors Into Staging After Treatment 

Elizabeth A. Mittendorf, MD, PhD1; Jose Vila, MD1; Susan L. Tucker, PhD2; ….; W. Fraser Symmans, MD6; Aysegul A. Sahin, MD6; Gabriel N. Hortobagyi, MD3; Kelly K. Hunt, MD
JAMA Oncol. Published online March 17, 2016.              http://dx.doi.org:/10.1001/jamaoncol.2015.6478

Importance  We previously described and validated a breast cancer staging system (CPS+EG, clinical-pathologic scoring system incorporating estrogen receptor–negative disease and nuclear grade 3 tumor pathology) for assessing prognosis after neoadjuvant chemotherapy using pretreatment clinical stage, posttreatment pathologic stage, estrogen receptor (ER) status, and grade. Development of the CPS+EG staging system predated routine administration of trastuzumab in patients with ERBB2-positive disease (formerly HER2 or HER2/neu).

Objective  To validate the CPS+EG staging system using the new definition of ER positivity (≥1%) and to develop an updated staging system (Neo-Bioscore) that incorporates ERBB2 status into the previously developed CPS+EG.

Design, Setting, and Participants  Retrospective review of data collected prospectively from January 2005 through December 2012 on patients with breast cancer treated with neoadjuvant chemotherapy at The University of Texas MD Anderson Cancer Center.

Main Outcomes and Measure  Prognostic scores were computed using 2 versions of the CPS+EG staging system, one with ER considered positive if it measured 10% or higher, the other with ER considered positive if it measured 1% or higher. Fits of the Cox proportional hazards model for the 2 sets of prognostic scores were compared using the Akaike Information Criterion (AIC). Status of ERBB2 was added to the model, and the likelihood ratio test was used to determine improvement in fit.

Results  A total of 2377 patients were included; all were women (median age, 50 years [range, 21-87 years]); ER status was less than 1% in 28.9%, 1% to 9% in 8.3%, and 10% or higher in 62.8%; 591 patients were ERBB2 positive. Median follow-up was 4.2 years (range, 0.5-11.7 years). Five-year disease-specific survival was 89% (95% CI, 87%-90%). Using 1% or higher as the cutoff for ER positivity, 5-year disease-specific survival estimates determined using the CPS+EG stage ranged from 52% to 98%, thereby validating our previous finding that the CPS+EG score facilitates more refined categorization into prognostic subgroups than clinical or final pathologic stage alone. The AIC value for this model was 3333.06, while for a model using 10% or higher as the cutoff for ER positivity, it was 3333.38, indicating that the model fits were nearly identical. The improvement in fit of the model when ERBB2 status was added was highly significant, with 5-year disease-specific survival estimates ranging from 48% to 99% (P < .001). Incorporating ERBB2 into the staging system defined the Neo-Bioscore, which provided improved stratification of patients with respect to prognosis.

Conclusions and Relevance  The Neo-Bioscore improves our previously validated staging system and allows its application in ERBB2-positive patients. We recommend that treatment response and biologic markers be incorporated into the American Joint Committee on Cancer staging system.

 

Transforming Breast Cancer Treatment

Landmark preclinical study cured lung metastases in 50 percent of breast cancers by making nanoparticles inside the tumor.

http://www.technologynetworks.com/news.aspx?ID=189462

A team of investigators from Houston Methodist Research Institute may have transformed the treatment of metastatic triple negative breast cancer by creating the first drug to successfully eliminate lung metastases in mice.

The majority of cancer deaths are due to metastases to the lung and liver, yet there is no cure. Existing cancer drugs provide limited benefit due to their inability to overcome biological barriers in the body and reach the cancer cells in sufficient concentrations. Houston Methodist nanotechnology and cancer researchers have solved this problem by developing a drug that generates nanoparticles inside the lung metastases in mice.

In this study, 50 percent of the mice treated with the drug had no trace of metastatic disease after eight months. That’s equivalent to about 24 years of long-term survival following metastatic disease for humans.

Due to the body’s own defense mechanisms, most cancer drugs are absorbed into healthy tissue causing negative side effects, and only a fraction of the administered drug actually reaches the tumor, making it less effective, said Mauro Ferrari, Ph.D, president and CEO of the Houston Methodist Research Institute. This new treatment strategy enables sequential passage of the biological barriers to transport the killing agent into the heart of the cancer. The active drug is only released inside the nucleus of the metastatic disease cell, avoiding the multidrug resistance mechanism of the cancer cells. This strategy effectively kills the tumor and provides significant therapeutic benefit in all mice, including long-term survival in half of the animals.

This finding comes 20 years after Ferrari started his work in nanomedicine. Ferrari and Haifa Shen, M.D., Ph.D., are co-senior authors on the paper, which describes the action of the injectable nanoparticle generator (iNPG), and how a complex method of transporting a nano-version of a standard chemotherapy drug led to never before seen results in mice models with triple negative breast cancer that had metastasized to the lungs.

“This may sound like science fiction, like we’ve penetrated and destroyed the Death Star, but what we discovered is transformational. We invented a method that actually makes the nanoparticles inside the cancer and releases the drug particles at the site of the cellular nucleus. With this injectable nanoparticle generator, we were able to do what standard chemotherapy drugs, vaccines, radiation, and other nanoparticles have all failed to do,” said Ferrari.

Houston Methodist has developed good manufacturing practices (GMP) for this drug and plans to fast-track the research to obtain FDA-approval and begin safety and efficacy studies in humans in 2017.

“I would never want to overpromise to the thousands of cancer patients looking for a cure, but the data is astounding,” said Ferrari, senior associate dean and professor of medicine, Weill Cornell Medicine. “We’re talking about changing the landscape of curing metastatic disease, so it’s no longer a death sentence.”

The Houston Methodist team used doxorubicin, a cancer therapeutic that has been used for decades but has adverse side effects to the heart and is not an effective treatment against metastatic disease. In this study, doxorubicin was packaged within the injectable nanoparticle generator that is made up of many components.

Shen, a senior member of the department of nanomedicine at Houston Methodist Research Institute, explains that each component has a specific and essential role in the drug delivery process. The first component is the nanoporous silicon material that naturally degrades in the body. The second component is a polymer made up of multiple strands that contain doxorubicin. Once inside the tumor, the silicon material degrades, releasing the strands. Due to natural thermodynamic forces, these strands curl-up to form nanoparticles that are taken up by the cancer cells. Once inside the cancer cells, the acidic pH close to the nucleus causes the drug to be released from the nanoparticles. Inside the nucleus, the active drug acts to kill the cell.

“If this research bears out in humans and we see even a fraction of this survival time, we are still talking about dramatically extending life for many years. That’s essentially providing a cure in a patient population that is now being told there is none,” said Ferrari, who holds the Ernest Cockrell Jr. Presidential Distinguished Chair and is considered one of the founders of nanomedicine and oncophysics (physics of mass transport within a cancer lesion).

The Houston Methodist team is hopeful that this new drug could help cancer physicians cure lung metastases from other origins, and possibly primary lung cancers as well.

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3D mapping of genome in combine FISH and RNAi

Larry H. Bernstein, MD, FCAP, Curator

LPBI

Cellular factors that shape the 3D landscape of the genome identified

http://www.nih.gov/news/health/aug2015/nci-13.htm

Researchers, using novel large-scale imaging technology, have mapped the spatial location of individual genes in the nucleus of human cells and identified 50 cellular factors required for the proper three-dimensional (3D) positioning of genes. These spatial locations play important roles in gene expression, DNA repair, genome stability, and other cellular activities. The study, by scientists at the National Cancer Institute (NCI), part of the National Institutes of Health, appeared August 13, 2015, in Cell.

One of the fundamental properties of the genomes of higher organisms is the non-random arrangement of DNA in the cell nucleus. Researchers have long known that most genes occupy preferred 3D positions in the nucleus and that the location of genes matters for their function, but it has been difficult to determine the molecular players and mechanisms that determine the positions. Although genes can be visualized routinely and their positions determined using fluorescence in situ hybridization, or FISH, this mapping method has traditionally been limited to the analysis of a few samples at a time and cannot be used for large-scale genome mapping.

NCI researchers, in close collaboration with NCI’s High-Throughput Imaging Facility, which was established earlier this decade, have developed a method called HIPMap (High-throughput Imaging Position Mapping) that makes the large-scale determination of 3D gene positions possible. This method uses an optimized FISH detection protocol, fully automated microscopy, and combines it with sophisticated computational image analysis that delivers high-precision gene mapping information for thousands of samples in a single experiment.

In the study, NCI researchers, led by Tom Misteli, Ph.D., associate director, NCI Center for Cancer Research, used HIPMap and a method known as RNA interference (RNAi) knockdown to screen nearly 700 proteins in the nucleus to identify those that are involved in the 3D positioning of several human genes. RNAi knockdown uses RNA molecules to block the production of specific proteins in cells.

By collecting data continuously from automated microscopes for 27 days and then analyzing more than three million data points, the scientists were able to identify 50 cellular factors that determine the location of genes in the cell nucleus. This list provides the basis for further investigation of the molecular mechanisms of genome organization.

“The importance of HIPMap is that it is a starting point for numerous applications, including cancer biology,” said Misteli. “In addition to addressing basic questions about the mechanisms of how genomes are organized in intact cells, the ability to map gene positions in a large number of samples and cells has already been used to detect very rare chromosome translocation events in cancer and to ask what cellular factors determine where chromosomes break.”  During translocations, chromosomes break and reattach, which can cause the fusion of otherwise unconnected genes, resulting in hybrid genes whose protein products may contribute to the development of cancer.

As an example of the implications of HIPMap, Misteli pointed to a study from his lab published last month (Burman et al., Genes and Development. July 1, 2015).  In that study researchers used a method derived from HIPMap to probe mechanisms that contribute to the susceptibility of chromosomes to break and form a cancer-causing translocation between the NPM1 gene and the ALK gene in a cancer known as anaplastic large cell lymphoma. Another possible application of HIPMap is in cancer diagnostics. The researchers have previously shown that some genes assume distinct positions in cancer. As a result, the 3D positions of genes could be used as diagnostic markers in diseases such as breast cancer and prostate cancer.

“HIPMap will be a powerful tool in many ongoing efforts to map the genome in 3D space and to translate the findings from these studies to cancer biology,” Misteli concluded.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health®

Reference

Shachar S, Voss TC, Pegoraro G, Sciascia N, Misteli T. Identification of Gene Positioning Factors Using High-throughput Imaging Mapping. Cell. August 13, 2015. DOI: 10.1016/j.cell.2015.07.035.

Stephen J. Williams, PhD

It is interesting they were able to complete this work and develop this technology which I see has other applications than which they suggested. It has been shown how certain factors (HIRAII) accumulate in certain areas of the chromatin during earliest stages of transformation and facilitate massive chromatin remodeling. That genetic information is spatially regulated, particular specific genes, and their technology can map it in a way I feel which is more accurate than probe methodologies or common sequencing methodologies is exciting news. however it may be difficult to use this as an early detection platform, unless it is done post-biopsy. A proceedure, possibly sensor based would need to be developed as well an an invitral imaging methodology.
The particular interesting application I would find would be the detection of insertion sites of genetic therapy. Currently it requires a long procedure involving knowledge of flanking sequences but this mapping procedure would help greatly, especially as I see it in determining insertion sites in development of personalized CART therapy. I would be interested if this group have been able to transfect in a gene and use their HIMAP to determine the spatial insertion site. Will be nice to see this work evolve..

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Larry H. Bernstein, MD, FCAP, Curator

http://pharmaceuticalinnovation/6/7/2014/Omega-3 fatty acids, depleting the source, and protein insufficiency in renal disease

 

This article is concerned only with updating the importance of key nutrients for maintenance of health. Nutritional losses are associated with memory loss, impaired immunity, and loss of lean body mass.

 

Low levels of omega-3 fatty acids may cause memory problems

Disease and ConditionsGeneral Diet • Tags: Alzheimer’s diseaseAmerican Academy of NeurologyDocosahexaenoic acidMagnetic resonance imagingNeurologyOmega-3 fatty acid, United States Environmental Protection AgencyUniversity of California Los Angeles

09 Mar 2012

 

ST. PAUL, Minn. – A diet lacking in omega-3 fatty acids, nutrients commonly found in fish, may cause your brain to age faster and lose some of its memory and thinking abilities, according to a study published in the February 28, 2012, print issue of Neurology®, the medical journal of the American Academy of Neurology. Omega-3 fatty acids include the nutrients called docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA).

salmon dinner

salmon dinner

 

 

 

 

 

 

 

 

 

“People with lower blood levels of omega-3 fatty acids had lower brain volumes that were equivalent to about two years of structural brain aging,” said study author Zaldy S. Tan, MD, MPH, of the Easton Center for Alzheimer’s Disease Research and the Division of Geriatrics, University of California at Los Angeles.

For the study, 1,575 people with an average age of 67 and free of dementia underwent MRI brain scans. They were also given tests that measured mental function, body mass and the omega-3 fatty acid levels in their red blood cells.

The researchers found that people whose DHA levels were among the bottom 25 percent of the participants had lower brain volume compared to people who had higher DHA levels. Similarly, participants with levels of all omega-3 fatty acids in the bottom 25 percent also scored lower on tests of visual memory and executive function, such as problem solving and multi-tasking and abstract thinking.

Related articles

 

Mechanisms of muscle wasting in chronic kidney disease.

Xiaonan H WangWilliam E Mitch

Nature Reviews Nephrology (Impact Factor: 7.94). 07/2014; DOI: 10.1038/nrneph.2014.112

Source: PubMed

ABSTRACT In patients with chronic kidney disease (CKD), loss of cellular proteins increases the risks of morbidity and mortality. Persistence of muscle protein catabolism in CKD results in striking losses of muscle proteins as whole-body protein turnover is great; even small but persistent imbalances between protein synthesis and degradation cause substantial protein loss. No reliable methods to prevent CKD-induced muscle wasting currently exist, but mechanisms that control cellular protein turnover have been identified, suggesting that therapeutic strategies will be developed to suppress or block protein loss. Catabolic pathways that cause protein wasting include activation of the ubiquitin-proteasome system (UPS), caspase-3, lysosomes and myostatin (a negative regulator of skeletal muscle growth). These pathways can be initiated by complications associated with CKD, such as metabolic acidosis, defective insulin signalling, inflammation, increased angiotensin II levels, abnormal appetite regulation and impaired microRNA responses. Inflammation stimulates cellular signalling pathways that activate myostatin, which accelerates UPS-mediated catabolism. Blocking this pathway can prevent loss of muscle proteins. Myostatin inhibition could yield new therapeutic directions for blocking muscle protein wasting in CKD or disorders associated with its complications.

 

We’re Fishing the Oceans Dry. It’s Time to Reconsider Fish Farms.

Food and Agriculture Organization of the United Nations -State of World Fisheries and Aquaculture  2014

Food and Agriculture Organization of the United Nations -State of World Fisheries and Aquaculture 2014

 

 

 

 

 

 

 

 

 

 

 

 

Aquaculture has gotten much greener, with American innovators leading the way.

— Text by Maddie Oatman; video by Brett Brownell

| Wed Jul. 2, 2014 6:00 AM EDT    MotherJones.com

 

When I meet Kenny Belov mid-morning at San Francisco’s Fisherman’s Wharf, the boats that would normally be out at sea chasing salmon sit tethered to their docks. The steady breeze coursing through the bay belies choppier conditions farther out—so rough that the local fishermen threw in the towel for the fifth morning in a row. Belov scans the horizon as he explains this, feet away from the warehouse of his sustainable seafood company, TwoXSea. Because his business hinges on what local fishermen can bring in, he’s used to coping with wild fish shortages.

If we continue to fish at the current pace, some scientists predict we’ll be facing oceans devoid of edible marine creatures by 2050.

But unlike these fishermen, Belov has a stash of treasure in his warehouse, as he soon shows me: a golf-cart-size container of plump trout, their glossy bodies still taut from rigor mortis. The night before, Belov drove north to Humboldt to help “chill kill” the fish by submerging them live into barrels of slushy ice water. Belov can count on shipments of these McFarland Springs trout every week—because he helped grow them himself on a farm.

For many consumers, aquaculture lost its appeal after unappetizing news spread about commercial fish farms—like fish feed’s pressure on wild resources, overflowing waste, toxic buildup in the water, and displacement of natural species. But consider this: Our appetite for seafood continues to rise. Globally, we’ve hungered for 3.2 percent more seafood every year for the last five decades, double the rate of our population. Yet more than four-fifths of the world’s wild fisheries are overexploited or fully exploited (yielding the most fish possible with no expected room for growth). Only 3 percent of stocks are considered underexploited—meaning they have any significant room for expansion. If we continue to fish at the current pace, some scientists predict we’ll be facing oceans devoid of edible marine creatures by 2050.

Aquaculture could come to the rescue. The Food and Agriculture Organization of the United Nations predicts that farmed fish will soon surpass wild-caught; by 2030, aquaculture may produce more than 60 percent of fish we consume as food.

Food and Agriculture Organization of the United Nations “State of World Fisheries and Aquaculture” 2014 report

One of the most pressing concerns about aquaculture, though, is that many farmed fish are raised on a diet of 15 million tons a year of smaller bait fish—species like anchovies and menhaden. These bait—also known as forage fish—are ground up and converted into a substance called fishmeal. It takes roughly five pounds of them to produce one pound of farmed salmon. Bait fish are also used for nonfood products like pet food, makeup, farm animal feed, and fish oil supplements.

Forage fish are a “finite resource that’s been fully utilized.”

It may appear as though the ocean enjoys endless schools of these tiny fish, but they too have been mismanaged, and their populations are prone to collapse. They’re a “finite resource that’s been fully utilized,” says Mike Rust of NOAA’s fisheries arm. Which is disturbing, considering that researchers like those at Oceana argue that forage fish may play an outsize role in maintaining the ocean’s ecological balance, including by contributing to the abundance of bigger predatory fish.

And that’s where Belov’s trout come in: Though he swears no one can taste the difference, his fish are vegetarians. That means those five pounds of forage fish can rest easy at sea. It also means that the trout don’t consume some of the other rendered animal proteins in normal fishmeal pellets: bone meal, feather meal, blood meal, and chicken byproducts.

Belov and McFarland Springs’ owner David McFarland were inspired to switch to vegetarian feed in part by Rick Barrows, a USDA researcher. About six years ago, recounts Barrows, several USDA studies confirmed that fish rely on nutrients—vitamins, minerals, fatty acids, and protein—rather than fishmeal or fish oil, to thrive. If those nutrients could be found in other products, including purely plant-based substances, then aquaculture might not be so dependent on feeding fish other smaller fish.

Barrows and team began to test about 50 potential materials a year, and now have a database of 140 that anyone can browse through online. Belov was one of their first commercial partners. The plant-based food fed to McFarland Springs’ trout consists of a hearty blend of marine algae, freshwater micro algae, vitamins, minerals, flax, flax oil, corn, and nut waste. The resulting complete protein means the trout’s omega 3s are high and their omega 6s are low—a ratio that’s said to enhance anti-inflammatory properties. And “they don’t have the concentration of heavy metals that come from the bait fish,” Belov says. I took one of his rosy fillets home and turned it into trout lox; find the recipe here.

McFarland Springs manages the trout’s waste by funneling it out into a natural sagebrush pasture where it composts the soil.

Belov’s fish feed includes California nuts that are too broken or disfigured to be sold.

Barrows thinks region-specific material for this type of feed offers the most potential. For instance, his team learned that around 5 percent of California nuts can’t be sold because they’re broken or disfigured. They realized they could repurpose excess nut parts for the trout feed; the nut bits helped round out the complete protein. Lately, Barrows has become especially excited about turning barley surplus from the beer industry—which comes at a cheap price in Montana, where he’s based—into a feed-grade concentrate for trout feed.

“You can get just as much growth rate out of fishmeal-free feeds as fishmeal,” says Barrows. And his lab has proven as much with eight different fish species: cobia, Florida pompano, coho salmon, Atlantic salmon, walleye, yellowtail, and White seabass.

But the price difference still stands in the way for many fish farmers. Belov pays slightly more than $1/pound for his plant-based feed, whereas fishmeal pellets average around $0.71/pound. He sells his trout for $6.95/pound, about a dollar more than conventional. But he’s well positioned in the affluent Bay Area, and he usually sells out of his McFarland Springs trout well before the end of each week. As innovation continues in the realm of plant-based feeds, he’s hopeful, along with Barrows, that the price of the pellets will continue to drop.

Here in the United States, we consume plenty of farmed fish already, but only 5 percent of it is sourced domestically. “If we didn’t import so much farmed seafood,” implored Four Fish author Paul Greenberg in a recent New York Times op-ed, “we might develop a viable, sustainable aquaculture sector of our own.” It doesn’t just boil down to economics: The locations we generally export from, like China and South Asia, don’t have near the stringent environmental and health regulations as the US. “Growing more seafood at home would help with trade deficit, but also we could control the safety more,” says Barrows.

Though our current aquaculture sector is relatively tiny, US farmers are in a better position to innovate, because we have a sophisticated animal nutrition research center and feed sector, says NOAA’s Rust. “We’re the leading technical country in the world on feed.”

Belov wasn’t always open to aquaculture, and he still feels that fish—such as some salmon—with healthy wild fisheries attached to them should never be farmed. That way, environmentally responsible fishermen can stay in business. His long-term strategy for sustainable seafood? Draw from the “amazing [wild] fisheries that exist, and then you backfill with intelligent aquaculture, and yes, you can feed the planet with sustainable marine products.” Which may take more work, but as he puts it, “We depleted the ocean. It wasn’t anybody else’s fault. So it’s our job to fix it.”

 

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Importance of Omega-3 Fatty Acids in Reducing Cardiovascular Disease

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

UPDATED on 7/24/2018

Omega-3 fats Supplements Effect on Cardiovascular Health: EPA and DHA has little or no effect on Mortality or Cardiovascular Health

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/07/24/omega-3-fats-supplements-effect-on-cardiovascular-health-epa-and-dha-has-little-or-no-effect-on-mortality-or-cardiovascular-health/

 

The available evidence for cardiovascular effects of n-3 polyunsaturated fatty acid (PUFA) consumption has been reviewed here, focusing on long chain (seafood) n-3 PUFA, including their principal dietary sources, effects on physiological risk factors, potential molecular pathways and bioactive metabolites, effects on specific clinical endpoints, and existing dietary guidelines. Major dietary sources include fatty fish and other seafood. n-3 PUFA consumption lowers plasma triglycerides, resting heart rate, and blood pressure and might also improve myocardial filling and efficiency, lower inflammation, and improve vascular function. Experimental studies demonstrate direct anti-arrhythmic effects, which have been challenging to document in humans. n-3 PUFA affect a myriad of molecular pathways, including alteration of physical and chemical properties of cellular membranes, direct interaction with and modulation of membrane channels and proteins, regulation of gene expression via nuclear receptors and transcription factors, changes in eicosanoid profiles, and conversion of n-3 PUFA to bioactive metabolites. In prospective observational studies and adequately powered randomized clinical trials, benefits of n-3 PUFA seem most consistent for coronary heart disease mortality and sudden cardiac death. Potential effects on other cardiovascular outcomes are less-well-established, including conflicting evidence from observational studies and/or randomized trials for effects on nonfatal myocardial infarction, ischemic stroke, atrial fibrillation, recurrent ventricular arrhythmias, and heart failure. Research gaps include the relative importance of different physiological and molecular mechanisms, precise dose-responses of physiological and clinical effects, whether fish oil provides all the benefits of fish consumption, and clinical effects of plant-derived n-3 PUFA. Overall, current data provide strong concordant evidence that n-3 PUFA are bioactive compounds that reduce risk of cardiac death. National and international guidelines have converged on consistent recommendations for the general population to consume at least 250 mg/day of long-chain n-3 PUFA or at least 2 servings / week of oily fish.

Source References:

http://content.onlinejacc.org/article.aspx?articleid=1146941

http://www.ncbi.nlm.nih.gov/pubmed/17047219

http://www.ncbi.nlm.nih.gov/pubmed/18614744

http://www.ncbi.nlm.nih.gov/pubmed/19364995

http://www.ncbi.nlm.nih.gov/pubmed/16172267

Other articles related to this topic were published on this Open Access Online Scientific Journal, including the following:

Reversal of Cardiac mitochondrial dysfunction

Larry H Bernstein, MD, FACP, RN 04/14/2013

https://pharmaceuticalintelligence.com/2013/04/14/reversal-of-cardiac-mitochondrial-dysfunction/

Can resolvins suppress acute lung injury?

Larry H Bernstein, MD, FACB, RN 03/06/2013

https://pharmaceuticalintelligence.com/2013/03/06/can-resolvins-suppress-acute-lung-injury/

Calcium (Ca) supplementation (>1400 mg/day): Higher Death Rates from all Causes and Cardiovascular Disease in Women

Aviva Lev-Ari, PhD., RN 02/19/2013

https://pharmaceuticalintelligence.com/2013/02/19/calcium-ca-supplementation-1400-mgday-higher-death-rates-from-all-causes-and-cardiovascular-disease-in-women/

Endothelial Function and Cardiovascular Disease

Larry H Bernstein, MD, FCAP, Pathologist, Contributor, RN 10/25/2012

https://pharmaceuticalintelligence.com/2012/10/25/endothelial-function-and-cardiovascular-disease/

Mediterranean Diet is BEST for patients with established Heart Disorders

Aviva Lev-Ari, PhD, RN 10/15/2012

https://pharmaceuticalintelligence.com/2012/10/15/mediterranean-diet-is-best-for-patients-with-established-heart-disorders/

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