5 Ways to Start Pleasing Yourself Before Pleasing Others.


A man cannot be comfortable without his own approval. ~Mark Twain

Being a people pleaser has been a chronic issue for me for years, but I think I’ve finally nailed how to stop this self-effacing behavior. When I look back I could attribute it to many things. Maybe my tendency to please others stems from being the 3rd child, and having a brother who was ready to pounce on me at any moment. Or maybe it’s connected to the approval and love I endlessly sought from my neglecting parents. My selflessness may also be rooted in my deep fear of rejection and strong desire to be accepted.

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This kind of “skill”, putting others needs before your own, can develop in a variety of contexts and life circumstances, and without your awareness. However, there is usually one common denominator that will help you get to the bottom of this issue without too much digging in your past.

Your need to please others is essentially a defense against the fear of abandonment.

If you are just nice enough, accommodating enough, easy enough, quiet enough, supportive enough, agreeable enough, and available enough, then the people in your life won’t leave.

Your ability to please others guarantees you a spot. Staying in their good graces, being on their good side, and acting obediently is an assurance that they won’t find a reason to discard you.

I know this sounds sad and pathetic, but it’s all in the name of love. You want and deserve to be loved, but not at the expense of yourself. This kind of love embodies an unconscious contract, and involves an exchange that never ends up being fair or even.

Being a people pleaser puts you at risk for becoming resentful, losing your sense of self, and for not being able to share your thoughts and feelings openly. You also can become a doormat by letting people walk all over you leading to a loss of self-respect and self-value. In your love relationships you will become exhausted and depleted, and you will wonder why it feels so empty.

I know it’s not pretty; I’ve been there. The good news is that there are some clear steps you can take to change.

Here are 5 ways to start pleasing yourself instead of others.

1. Uncover your fears

Before anything else you need to figure out what you are afraid of. Is it disappointing others? Losing love? Not being liked? Once you know what you are defending against you will be able to work through these issues, which most likely stem from your past.

2. Learn to say no

The word no has a negative connotation most of the time, but it’s actually a way to set a boundary. Even a toddler uses the word no to differentiate his sense of self. It’s hard to say no, and sometimes we can’t, but drawing the line in the sand when we need to is a healthy practice, and it lets other people know our limits.

3. Speak Up

People pleasers tend to have a hard time expressing themselves openly and honestly. It’s scary to share your feelings when you think they will cause conflict or drive the other person away. Rocking the boat, and upsetting the status quo is a natural and healthy part of growing in your relationships. You will need to work on speaking up for yourself and taking a stand if necessary. It will feel harsh at first, but you’ll get used to it soon enough.

4. Come from a place of desire (not obligation)

When you are trying to learn how to set boundaries and say no you will be forced to really ask yourself what you want and need. This may be something you have never considered before, so it will seem selfish and weird at first. Make choices as opposed to fulfilling obligations. There are always things you have to do, but you are always choosing.

5. Know who your dealing with

If you’ve been a pleaser for a while then the people in your life will be used to it. Some will automatically respect your new way of relating, but others will resist it. If there are people who simply cannot accept your limits and boundaries, then you might want to rethink these relationships. Some relationships work for a reason, but the reason isn’t always healthy.

Source: purpose fairy

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Climate Change and Violence.


An analysis of 60 studies finds that warmer temperatures and extreme rainfall lead to a rise in violence.

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In the coming decades, the world’s changing climate could herald a rise in violence at every scale—from individuals to nations, from assault to war—according to a comprehensive new analysis of the link between climate and conflict.

Analyzing data from 60 earlier studies, Solomon Hsiang from the University of California, Berkeley, found that warmer temperatures and extremes in rainfall can substantially increase the risk of many types of conflict. For every standard deviation of change, levels of interpersonal violence, such as domestic violence or rape, rise by some 4 percent, while the frequency of intergroup conflict, from riots to civil wars, rise by 14 percent. Global temperatures are expected to rise by at least two standard deviations by 2050, with even bigger increases in the tropics.

“The paper is remarkably strong,” said Thomas Homer-Dixon, an environmental and political scientist at the University of Waterloo in Ontario, who was not involved in the study. “[It means] the world will be a very violent place by mid-century if climate change continues as projected.”

Hsiang, together with UC Berkeley colleagues Marshall Burke and Edward Miguel, focused only on studies that provided the strongest evidence for a causal connection. “The ideal thing would be to take two identical Earths, heat one up and watch how conflict evolves,” said Hsiang dryly. “We can’t do that, so we looked for these natural experiments.”

The researchers ignored any studies that compared levels of conflict between different countries, which also differ in their history, culture, and politics. Instead, they focused on data that revealed how violence rises and falls in a single place as climate changes.

For example, crime statistics in the United States reveal that the number of rapes, murders, or assaults increases on a hot day. Civil conflicts in the tropics become twice as frequent during the hot and dry years caused by El Niño events. Farmers in Brazil are more likely to invade each other’s land if they have a particularly wet or dry year. And Chinese dynasties all collapsed during long dry periods.

The team analyzed these studies and more using a common statistical framework to control for any biases on the part of the individual authors. Together, the data sets stretch back to 10,000 BC, and cover all major world regions. They represent the collective efforts of more than 190 researchers working across varied disciplines, from psychologists looking at the effects of temperature on aggressive behavior to archaeologists studying levels of violence in the ancient civilizations.

Despite this diversity, “we were shocked at how well the results from all these fields lined up,” said Hsiang. “Given how some people had been talking, we thought they’d be all over the map,” but the data consistently showed that temperature and rainfall affect violence, across locations, times and disciplines.

“This is a contested area and the convergence of results in this meta-analysis represents a significant step forward,” said Neil Adger, an environmental geographer at the University of Exeter, who was not involved in the study. He notes that responses to climate change, such as “widespread growing of biofuels or displacing populations to build dams” could exacerbate any increased propensity for conflict. “The impacts of climate change will factor large in the future, especially if the world is already fractured and unequal,” he said.

David Zhang, a geographer from the University of Hong Kong who was not involved in the study, said the results were robust and important. However, he noted that most of the data sets cover the last century, and the effects of climate on conflict, may have differed across centuries of human history. Hsiang acknowledges this gap, but said that a few century-spanning data sets have found similar trends.

“Another obvious criticism is that older societies may not be a good analogue for modern ones,” Hsiang added. For example, technological advances might help us to adapt to changing climate more effectively than past generations.

Hsiang also emphasized that climate is just one of many factors that influence the frequency of conflict, and that his study does not address why such a link between conflict and climate exists. Shifts in climate could change the availability of important resources like water or crops, leading to failing economies, weaker governments, and more incentives to fight or rebel. They could also lead to mass migration, rapid urbanization, or growing inequalities.

“We now want to understand what the underlying mechanisms are,” said Hsiang. “If we understand them, we could come up with policies that could decouple climate and conflict, which might help society to adapt. That’s a good reason to push the research ahead.”

Source: http://www.the-scientist.com

Asian Tiger Mosquito Could Spread U.S. Disease.


What’s striped black-and-white, packs a nasty bite and is a tireless spreader of disease? No, it’s not a B-movie horror creature — it’s the Asian tiger mosquito.

And though a relative newcomer to the American scene, experts now warn that this intruder is starting to create a fearsome buzz, with the potential to cause havoc across the United States. So far, however, it hasn’t led to widespread disease in this country.

 

“What we have here is an invasive daytime-feeding, disease-carrying mosquito that, since it first arrived on the East Coast in the 1980s, has been pretty aggressive in mowing down its natural competitors,” said Gabe Hamer, a clinical assistant professor in the department of entomology at Texas A&M University. “And now it’s really starting to move through the country in full force.”

“That makes it, at the very least, a nuisance and an annoyance,” Hamer explained. “And at worst, a serious vector for major pathogens.”

On its Asian home turf, the mosquito is a well-known carrier of dengue fever, with West Nile feveryellow fever, and encephalitis among the other debilitating illnesses for which it has been pegged as a transmitter.

According to the U.S. Centers for Disease Control and Prevention, the mosquito has so far been identified as a host for five different viruses in the United States. Two of those — encephalomyelitis and Cache Valley — can infect humans, while the others are a threat to dogs, cats, birds and other animals.

But U.S. experts are perhaps most alarmed that this mosquito potentially could become a prime North American vector for a particularly nasty joint and muscle pain illness for which there is neither a vaccine nor treatment: the Chikungunya virus.

Such concerns have escalated in light of recent research, such as that funded by the U.S. National Institute for Food and Agriculture, and reported in the January issue ofPLoS Neglected Tropical Diseases, which cautions that an imminent mosquito-driven American outbreak of the Chikungunya virus is a very real threat.

“The ongoing invasion of the Asian tiger mosquito in the U.S.A. represents an important risk,” agreed Diego Ruiz-Moreno, a postdoctoral associate in the department of ecology and evolutionary biology at Cornell University, who led the recent study. “Mainly because of the potential for disease to spread.”

Otherwise known as Aedes albopictus, the CDC notes that the Asian tiger mosquito was first spotted on the U.S. mainland in 1985. Since that initial Houston sighting, it has spread across 26 states, moving as far north as Chicago, as far east as Pennsylvania and New Jersey, as far west as Nebraska, and across a broad swath of the South, including Florida, Georgia, South Carolina and Tennessee.

Add now, Hamer said, California has been added to the list.

“The thing about this particular species is that it breeds and travels very well in small warm container environments,” with an uncanny ability to adapt and thrive in shifting temperatures, he explained. “And it turns out that humans are really good at providing those spaces. A tire, a flower pot, a bucket, urns at cemeteries. All these are classic holders of stagnant water, which is all they need to hop from one country to another, one state to another.”

And so, Hamer noted, “it’s been going everywhere. Europe, certain parts of Africa, South America, and now here,” where its aggressive mating habits have run roughshod over other local mosquito populations (such as the yellow fever mosquito), essentially replacing one illness-bearing mosquito threat with another.

But has the Asian tiger mosquito’s troublesome potential really lived up to its hype?

“I would say that for the moment, while the concern is real and we should be paying a lot of attention to this particular mosquito, so far it doesn’t seem to be playing a major pathogen-spreading role in the U.S.,” Hamer suggested.

“Chikungunya hasn’t come to the U.S. yet, and that’s comforting. At the same time, this is a very aggressive mosquito that feeds during the day, rather than from dusk to dawn, which is different from the way West Nile virus was spread, by a mosquito that fed at night. So we’re talking about the need for a kind of all-day vigilance against getting bitten that the American public is not really familiar with,” he pointed out.

“So the bottom line is that if chikungunya does show up, this mosquito could be the vector for it,” Hamer said. “And that means it’s important that we have protective virus surveillance up and running throughout the country, which we already do. So that once things show up we can react quickly.”

But as experts watch and wait, what can people do to protect themselves?

According to Ruiz-Moreno: “The best strategy is to reduce exposure to potentially infective mosquitoes, either by avoiding contact or reducing mosquito population in the wild. At home, we recommend removing all sources of standing water. And when going outside we need to wear insect repellent and cover up with long sleeves and pants to avoid mosquito bites.”

Source: medicinenet.com

 

Cancer cells change while moving throughout the body.


A major focus of contemporary cancer research is on how to stop or fight metastasis – the spread of a cancer from one organ or part to another non-adjacent organ or part.

For the majority of cancer patients, it’s not the primary tumor that is deadly, but the spread or “metastasis” of cancer cells from the primary tumor to secondary locations throughout the body that is the problem. That’s why a major focus of contemporary cancer research is how to stop or fight metastasis.

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Previous lab studies suggest that metastasizing cancer cells undergo a major molecular change when they leave the primary tumor – a process called epithelial-to-mesenchymal transition (EMT). As the cells travel from one site to another, they pick up new characteristics. More importantly, they develop a resistance to chemotherapy that is effective on the primary tumor. But confirmation of the EMT process has only taken place in test tubes or in animals.

In a new study, published in the Journal of Ovarian Research, Georgia Tech scientists have direct evidence that EMT takes place in humans, at least in ovarian cancer patients. The findings suggest that doctors should treat patients with a combination of drugs: those that kill cancer cells in primary tumors and drugs that target the unique characteristics of cancer cells spreading through the body.

The researchers looked at matching ovarian and abdominal cancerous tissues in seven patients. Pathologically, the cells looked exactly the same, implying that they simply fell off the primary tumor and spread to the secondary site with no changes. But on the molecular level, the cells were very different. Those in the metastatic site displayed genetic signatures consistent with EMT. The scientists didn’t see the process take place, but they know it happened.

“It’s like noticing that a piece of cake has gone missing from your kitchen and you turn to see your daughter with chocolate on her face,” said John McDonald, director of Georgia Tech’s Integrated Cancer Research Center and lead investigator on the project. “You didn’t see her eat the cake, but the evidence is overwhelming. The gene expression patterns of the metastatic cancers displayed gene expression profiles that unambiguously identified them as having gone through EMT.”

The EMT process is an essential component of embryonic development and allows for reduced cell adhesiveness and increased cell movement.

According to Benedict Benigno, collaborating physician on the paper, CEO of the Ovarian Cancer Institute and director of gynecological oncology at Atlanta’s Northside Hospital, “These results clearly indicate that metastasizing ovarian cancer cells are very different from those comprising the primary tumor and will likely require new types of chemotherapy if we are going to improve the outcome of these patients.”

Ovarian cancer is the most malignant of all gynecological cancers and responsible for more than 14,000 deaths annually in the United States alone. It often reveals no early symptoms and isn’t typically diagnosed until after it spreads.

“Our team is hopeful that, because of the new findings, the substantial body of knowledge that has already been acquired on how to block EMT and reduce metastasis in experimental models may now begin to be applied to humans,” said Georgia Tech graduate student Loukia Lili, co-author of the study.

Source: Georgia Tech University

Scientists Discover That Plants Communicate via Symbiotic Root Fungi.


Human arrogance has always assumed we are evolutionarily superior to plants, but it appears that modern science may be the antidote to this egocentric view.

Researchers in the UK have discovered an extensive underground network connecting plants by their roots, serving as a complex interplant communication system… a “plant Internet,” if you will.

One organism is responsible for this amazing biochemical highway: a type of fungus called mycorrhizae. Researchers from the University of Aberdeen devised a clever experiment to isolate the effects of these extensive underground networks. They grew sets of broad bean plants, allowing some to develop mycorrhizal nets, but preventing them in others.

They also eliminated the plants’ normal through-the-air communication by covering the plants with bags. Then they infested some of the plants with aphids. The results were remarkable.1

Most people have no idea how important mycorrhizal fungi are for plant growth. They really are one of the keys to successful growth of plants. In my own garden, I just purchased a 15 gallon vortex compost brewer in which I grow these fungi in large quantities for my ornamental and edible landscape.

Underground Communications Network Thwarts Infestation

The aphid-infested plants were able to signal the other plants, connected through mycorrhizae, of an imminent attack—giving them a “heads up” and affording them time to mount their own chemical defenses in order to prevent infestation.

In this case, the alerted bean plants deployed aphid-repelling chemicals and other chemicals that attract wasps, which are aphids’ natural predators. The bean plants that were not connected received no such warning and became easy prey for the pesky insects.

This study is not the first to discover plant communication along mycorrhizal networks. A 2012 article in the Journal of Chemical Ecology describes mycorrhizae-induced resistance as part of plants’ systemic “immune response,” protecting them from pathogens, herbivores, and parasitic plants.2

And in 2010, Song et al published a report about the interplant communication of tomato plants, in which they wrote:3

CMNs [common mycorrhizal networks] may function as a plant-plant underground communication conduit whereby disease resistance and induced defense signals can be transferred between the healthy and pathogen-infected neighboring plants, suggesting that plants can ‘eavesdrop’ on defense signals from the pathogen-challenged neighbors through CMNs to activate defenses before being attacked themselves.”

Miles of Mycorrhizae in One Thimbleful of Soil

The name mycorrhiza literally means fungus-root.4 These fungi form a symbiotic relationship with the plant, colonizing the roots and sending extremely fine filaments far out into the soil that act as root extensions. Not only do these networks sound the alarm about invaders, but the filaments are more effective in nutrient and water absorption than the plant roots themselves—mycorrhizae increase the nutrient absorption of the plant 100 to 1,000 times.5

In one thimbleful of healthy soil, you can find several MILES of fungal filaments, all releasing powerful enzymes that help dissolve tightly bound soil nutrients, such as organic nitrogen, phosphorus, and iron. The networks can be enormous—one was found weaving its way through an entire Canadian forest, with each tree connected to dozens of others over distances of 30 meters.

These fungi have been fundamental to plant growth for 460 million years. Even more interesting, mycorrhizae can even connect plants of different species, perhaps allowing interspecies communication.6

More than 90 percent of plant species have these naturally-occurring symbiotic relationships with mycorrhizae, but in order for these CMNs to exist, the soil must be undisturbed. Erosion, tillage, cultivation, compaction, and other human activities destroy these beneficial fungi, and they are slow to colonize once disrupted. Therefore, intensively farmed plants don’t develop mycorrhizae and are typically less healthy, as a result.

Making Farming More Eco-friendly

The discovery that fungi may be providing plants with an early warning system has profound implications for how we grow our food. We may be able to arrange for “sacrificial plants” specifically designed for pest infestation so that the network can warn, and thereby arm, the rest of the crop.7 In order to feed the world’s increasing population, farmers must return to working WITH nature, instead of against it.

Raising food is really about building soil, and modern agricultural practices are degrading million year-old topsoils, without any attention to rebuilding them. Spreading toxic chemicals, monoculture, using genetically engineered seed, generating toxic runoff and destroying biodiversity are all examples of working against nature. Mycorrhizae not only assist the plants in staying vital and healthy, but they enrich the soil and improve its productivity, add organic matter, protect crops from drought, and increase the overall balance and resilience of the ecosystem.

Many fungi are as beneficial to people as they are to plants. Mushrooms are powerhouses when it comes to nutrition, with high-quality protein, enzymes, antioxidants, and B vitamins.

About 100 species of mushrooms are being studied for their health-promoting benefits, and about a half dozen really stand out for their ability to deliver a tremendous boost to your immune system. Studies have shown that mushrooms can combat infectious disease (including smallpox), inflammation, cancer and even help regenerate nerves. A compound from the Coriolus versicolor mushroom was recently found to significantly slow hemangiosarcoma in dogs, a deadly cancer.

Mushrooms are also nature’s recycling system, according to mycologist Paul Stamets. Various mushrooms can break down the toxins in nerve gas and clean up petroleum waste.

Mushrooms and their parent mycelium break down rocks and organic matter, turning them into soil. The mycelia, just like the mycorrhizal network, occupy landscapes in a web-like mat that, in some cases, stretches across thousands of acres. Stamets describes this intricate, branching network as “the Earth’s Internet” because it functions as a complex communication highway. There is also evidence mycelia are “sentient” beings that demonstrate the ability to learn. Speaking of cool and calculating…

Now that the secret’s out, companies are beginning to offer mycorrhizae to home gardeners and commercial farmers alike. If you have an organic garden, adding a sprinkle of mycorrhizae, along with good organic fertilizer, is a great way to ensure your garden will be the envy of your neighborhood.

For tips on how to use this in your garden at home, I recommend watching the “smiling gardener” video above. It’s important to remember that mycorrhizae must be applied to the roots of your plants. If you just sprinkle the granules onto the soil and they don’t make contact with the roots within about 48 hours, they’ll die and your efforts will be wasted. So, you can make a “tea” out of it and apply it as a spray, or you can rub a small amount directly onto the roots of your transplant. But it has to come into direct contact with some part of the root.

The only vegetable garden occupants that will not benefit from mycorrhizae are your brassicas (members of the mustard family, such as cabbage, broccoli, cauliflower, turnips, radishes, etc.), because they don’t allow this colonization.8 But all your other veggies will love you for it. The benefits will be even greater in a year or two, after the mycorrhizae really have a chance to grow and spread.

Also, remember to refrain from tilling and manipulating the soil. This isn’t necessary and is actually counterproductive, as it disrupts helpful organisms and crushes their tunnels.9 Just topdress your garden with a blend of good compost and topsoil each year, and leave the bed alone, which will allow those beneficial organisms to grow and flourish, undisturbed.

When you practice ecofriendly gardening, you greatly lessen your need for fertilizers and herbicides, reduce your need for watering, and reduce runoff and erosion, while giving your garden plants the best nutrition and resistance to disease. And best of all, a healthy veggie garden means more nutrients passed along to you!

Source: http://www.wakingtimes.com

The Perseid meteor shower… now appearing in the sky above you.


A celestial fireworks show peaks Monday and Tuesday as Earth passes though the dust of a comet’s tail.

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Humans around the world have witnessed the Perseid meteor shower every August for at least 2,000 years, with dozens of meteors streaking across the sky each hour.

Your view is best after midnight until just before sunrise. Get away from city lights, if possible, for the full effect. A waning crescent moon means less light in the sky to compete with the meteor display. Next year’s show will be dimmed by a full moon.

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The annual sky spectacular happens when our planet’s orbit around the sun passes near Comet Swift-Tuttle‘s path, which goes by every 130 years. The last close encounter with the comet was 20 years ago, but it left grains of dust in its wake.

Perseid meteor shower lights up sky

Amazing images of another meteor shower, the Orionid, October 2012

The bright streaks you see are “interplanetary dust” burning up as it collides with our atmosphere at about 133,000 mph, according to NASA micrometeoroid expert Diego Janches. “The fragments are either remnants from the solar system’s formation, or they are produced by collisions between asteroids or comets from long ago.”

“Each such fragment is approximately the size of a dime, but the more constant, sporadic meteoroids have been around much longer, breaking down over time into tiny fragments only about as wide as a piece of human hair,” according to NASA.gov.

While the meteor show is entertainment for most, it is a research opportunity for Janches and other NASA scientists. They’ll use radar systems around the globe to watch the fragments of sodium, silicon, calcium and magnesium enter the atmosphere.

“The small meteoroids feed the atmosphere with all these extra materials,” Janches said in a NASA.com posting. “They come in, release metallic atoms that get deposited in the mesosphere and then get pushed around from pole to pole by the general global circulation. So by using the metals as tracers, you can answer some important questions about the general composition and movement of the atmosphere.”

Source:CNN

 

 

Bariatric surgery yields genetic changes among patients with NAFLD.


Patients with nonalcoholic fatty liver disease who undergo bariatric surgery may experience DNA-altering effects that can reverse their disease symptoms, according to a recent study.

Researchers evaluated snap-frozen liver biopsies collected from 18 normal controls and 18 healthy obese, 12 obese with steatosis and 15 obese with NASH patients. Follow-up biopsies were performed in seven healthy obese patients, 10 with steatosis and six with NASH at 5 to 9 months after participants had undergone bariatric surgery.

Across the groups, 467 CpG loci were methylated differently at a false discovery threshold of q=.05, with the NASH and normal liver samples as the extreme groups in PCA and heatmap analysis. Nine of 294 genes annotated to these CpGs had 5% or more methylation difference between controls and the NASH group and more than 0.2 log2 change to mRNA expression (P<.05 after correction for multiple testing). These genes code for key enzymes for insulin and insulin-like signaling and intermediate metabolism.

Investigators observed a weak but significant inverse correlation in the changes to DNA methylation between NASH samples and controls before and after bariatric surgery in the CpG loci (P=.004). Methylation was partially reversible at the HOBX1PRKCZSLC38A10 and SECTM1 loci.

Paired analysis before and after surgery indicated 113 sites with different methylation (q=.05), with strong correlations observed between the differences in the control and NASH groups and bariatric surgery (P<2.2 x 10–16). Among the sites, 80 were mapped to 32 gene loci, and researchers noted differential expression of the gene encoding protein-tyrosine phosphatase epsilon before and post-surgery.

Binding sites for TFs GRP20 (P<3.8 x 10–233), SREBP2 (P<3.8 x 10–272), PGC1A (P<1 x 10–300) and ZNF274(P<1 x 10–300) were significantly enriched in the phenotype and bariatric remodeling groups.

“While the presented study is limited … it represents a genome-wide assessment of CpG methylation in NAFLD and its dynamic change induced by the weight loss after bariatric surgery,” the researchers concluded. “Some of the candidate epigenetic driver genes may represent attractive targets for future mechanistic studies and therapeutic inventions.”

Source: Endocrine Today

Bariatric surgery yields genetic changes among patients with NAFLD.


Patients with nonalcoholic fatty liver disease who undergo bariatric surgery may experience DNA-altering effects that can reverse their disease symptoms, according to a recent study.

Researchers evaluated snap-frozen liver biopsies collected from 18 normal controls and 18 healthy obese, 12 obese with steatosis and 15 obese with NASH patients. Follow-up biopsies were performed in seven healthy obese patients, 10 with steatosis and six with NASH at 5 to 9 months after participants had undergone bariatric surgery.

Across the groups, 467 CpG loci were methylated differently at a false discovery threshold of q=.05, with the NASH and normal liver samples as the extreme groups in PCA and heatmap analysis. Nine of 294 genes annotated to these CpGs had 5% or more methylation difference between controls and the NASH group and more than 0.2 log2 change to mRNA expression (P<.05 after correction for multiple testing). These genes code for key enzymes for insulin and insulin-like signaling and intermediate metabolism.

Investigators observed a weak but significant inverse correlation in the changes to DNA methylation between NASH samples and controls before and after bariatric surgery in the CpG loci (P=.004). Methylation was partially reversible at the HOBX1PRKCZSLC38A10 and SECTM1 loci.

Paired analysis before and after surgery indicated 113 sites with different methylation (q=.05), with strong correlations observed between the differences in the control and NASH groups and bariatric surgery (P<2.2 x 10–16). Among the sites, 80 were mapped to 32 gene loci, and researchers noted differential expression of the gene encoding protein-tyrosine phosphatase epsilon before and post-surgery.

Binding sites for TFs GRP20 (P<3.8 x 10–233), SREBP2 (P<3.8 x 10–272), PGC1A (P<1 x 10–300) and ZNF274(P<1 x 10–300) were significantly enriched in the phenotype and bariatric remodeling groups.

“While the presented study is limited … it represents a genome-wide assessment of CpG methylation in NAFLD and its dynamic change induced by the weight loss after bariatric surgery,” the researchers concluded. “Some of the candidate epigenetic driver genes may represent attractive targets for future mechanistic studies and therapeutic inventions.”

Source: Endocrine Today

GH replacement could delay progression of chronic HF.


New preliminary data demonstrate that growth hormone replacement therapy improved exercise and cardiac performance of patients with chronic heart failure and growth hormone deficiency.

Antonio Cittadini, MD, and colleagues conducted a single-blind study to investigate whether patients with both chronic heart failure (HF) and GH deficiency assigned GH replacement therapy could experience delays in the progression of chronic HF.

The findings suggest that “correction of [growth hormone] deficit improves exercise and cardiac performance of [chronic HF] patients in an enduring way,” the researchers wrote.

The researchers screened participants from a previous controlled, single blind, single-center study for GH deficiency. Of the 158 participants screened, 63 had GH deficiency and 56 were subsequently enrolled in the trial. Twenty-eight patients were randomly assigned standard therapy for chronic HF plus subcutaneous somatropin (rDNA origin; Saizen, Merck-Serono) at a dose of 0.012 mg/kg every second day. The other 28 patients were assigned standard therapy for chronic HF alone.

Follow-up was 4 years, and 17 patients in the GH group and 14 in the control group completed the study. The primary endpoint was peak oxygen consumption (VO2) because “it is a strong, independent predictor of [chronic HF] progression,” according to the study background. Peak VO2 improved in the GH group over 4 years, but not in the control group. The treatment effect was 7.1 ± 0.7 mL/kg/min in the GH group, which beat the researchers’ projected improvement of 4 mL/kg/min, vs. –1.8 ± 0.5 mL/kg/minin the control group (P<.001).

LV ejection fraction increased by 10 ± 3% in the growth-hormone group, but decreased by 2 ± 5% in the control group (P<.001). LV end-systolic volume index decreased by 22 ± 6 mL/m2 in the growth-hormone group and increased by 8 ± 3 ml/m2 in the control group (P<.001).

“The improvements in LV end-systolic volume and ejection fraction were [as] equally relevant [as improvements in peak VO2]; both are consolidated predictors of survival,” Cittadini and colleagues wrote.

The only adverse events reported by the GH group were two cases of arthralgia.

Given the limitations of a small study of this design with a large dropout rate, the association should be studied further in a large, multicenter, placebo-controlled, double blind trial, according to the researchers.

Source: Endocrine Today

Topotecan may be therapeutic for Angelman, Prader-Willi syndrome.


Recent data suggest that a chemotherapy agent used to treat metastatic cancers may also be therapeutic for Angelman or Prader-Willi syndrome, according to researchers.

“What determines whether you have Prader-Willi syndrome or Angelman syndrome is whether the maternal or paternal gene is missing,” Janine M. LaSalle, PhD, of the Medical Microbiology and Immunology, Genome Center, MIND Institute at the University of California, Davis, said in a press release. “These are the classic, textbookepigenetic disorders involving parental imprinting. It’s not just about the chromosomes, but it’s where — or who — they come from. In our study, we show that R-loops forming on the active paternal chromosome within the Prader-Willi region regulate imprinting of the Angelman gene, Ube3a, on the maternal chromosome.”

LaSalle and colleagues wrote that topotecan stabilized the arrangement of R-loops, or RNA:DNA hybrids, at G-skewed repeat elements within the paternal gene Snord116. This increases the loosening of chromatin and suppression of Ube3a-ATS expression, they added.

Furthermore, neural precursor cells from paternal Snord116 deletion mice demonstrated an increase in Ube3a-ATS levels in different neurons, and led to the reduction of topotecan’s effects compared with wild-type neurons, researchers wrote.

“Now we have a molecular mechanism for a proposed drug for a disease, so we can understand how it works and begin to tweak it to develop therapies,” researcher Weston T. Powell, PhD, also of the Medical Microbiology and Immunology, Genome Center, MIND Institute at the University of California, Davis, said in a press release.

Source: Endocrine Today