New human trial shows stem cells are effective for failing hearts: Bone marrow-derived stem cells injected directly into heart muscle

Patients with severe ischemic heart disease and heart failure can benefit from a new treatment in which stem cells found in bone marrow are injected directly into the heart muscle, according to research presented at the American College of Cardiology’s 63rd Annual Scientific Session.”Our results show that this stem cell treatment is safe and it improves heart function when compared to placebo,” said Anders Bruun Mathiasen, M.D., research fellow in the Cardiac Catherization Lab at Rigshospitalet University Hospital Copenhagen, and lead investigator of the study. “This represents an exciting development that has the potential to benefit many people who suffer from this common and deadly disease.”Ischemic heart disease, also known as coronary artery disease, is the number one cause of death for both men and women in the United States. It results from a gradual buildup of plaque in the heart’s coronary arteries and can lead to chest pain, heart attack and heart failure.The study is the largest placebo-controlled double-blind randomized trial to treat patients with chronic ischemic heart failure by injecting a type of stem cell known as mesenchymal stromal cells directly into the heart muscle.Six months after treatment, patients who received stem cell injections had improved heart pump function compared to patients receiving a placebo. Treated patients showed an 8.2-milliliter decrease in the study’s primary endpoint, end systolic volume, which indicates the lowest volume of blood in the heart during the pumping cycle and is a key measure of the heart’s ability to pump effectively. The placebo group showed an increase of 6 milliliters in end systolic volume.The study included 59 patients with chronic ischemic heart disease and severe heart failure. Each patient first underwent a procedure to extract a small amount of bone marrow. Researchers then isolated from the marrow a small number of mesenchymal stromal cells and induced the cells to self-replicate. Patients then received an injection of either saline placebo or their own cultured mesenchymal stromal cells into the heart muscle through a catheter inserted in the groin.”Isolating and culturing the stem cells is a relatively straightforward process, and the procedure to inject the stem cells into the heart requires only local anesthesia, so it appears to be all-in-all a promising treatment for patients who have no other options,” Mathiasen said.Although there are other therapies available for patients with ischemic heart disease, these therapies do not help all patients and many patients continue to face fatigue, shortness of breath and accumulation of fluid in the lungs and legs.Previous studies have shown mesenchymal stromal cells can stimulate repair and regeneration in a variety of tissues, including heart muscle. Mathiasen said in the case of ischemic heart failure, the treatment likely works by facilitating the growth of new blood vessels and new heart muscle.The study also supports findings from previous, smaller studies, which showed reduced scar tissue in the hearts of patients who received the stem cell treatment, offering additional confirmation that the treatment stimulates the growth of new heart muscle cells.The researchers will continue to monitor the patients to assess their long-term outcomes.”We hope that the improvements in heart pump function will not only improve the patients’ symptoms but also will result in increased survival for these severely diseased patients,” Mathiasen said.A larger, Phase III clinical trial will be needed to move toward approval of this treatment as a more widely used therapy for ischemic heart failure.”Our results should offer sufficient evidence that a larger trial is indeed warranted as a next step,” Mathiasen said.Story Source:The above story is based on materials provided by American College of Cardiology. Note: Materials may be edited for content and length.

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‘Best practices’ nutrition measurement for researchers

At first glance, measuring what the common fruit fly eats might seem like a trivial matter, but it is absolutely critical when it comes to conducting studies of aging, health, metabolism and disease. How researchers measure consumption can make all the difference in the accuracy of a study’s conclusions.Scientists from the Florida campus of The Scripps Research Institute (TSRI) have developed what amounts to a best practices guide to the most accurate way of measuring fruit fly food consumption that could lead to more informed research and better decisions about directions in further studies.”While our study isn’t the final technical reference on measuring fly food consumption, it will help guide researchers to think more carefully about nutrition and nutrient intake in their own studies,” said TSRI Assistant Professor William Ja, who led the study, which was published online ahead of print on March 30, 2014 by the journal Nature Methods.Researchers, Ja said, generally haven’t given sufficient thought to feeding and nutrient intake when it comes to measuring fruit fly behavior, metabolism and health.”If you’re making a huge effort to change an animal’s diet and trying to draw conclusions about what nutrition and nutrients do to animal health and lifespan,” he said, “then one of the most fundamental parameters is accurately measuring food intake.”TSRI Research Associate Sonali Deshpande, a first author of the study with graduate student Ariadna Amador and former TSRI Research Associate Gil Carvalho, underlined the importance of using the best measurement methods. “Drug studies, in particular, where compounds are added to fly food, are difficult to interpret without proper measurement of food and drug intake,” she said.In the study, the team determined that radioisotope labeling food is the most sensitive and consistently accurate feeding method now available — levels of accumulated isotope are later measured in the animals. This method’s main limitation appears to be underestimation of consumption due to excretion.For the most accurate measurement, the study suggested pairing radioisotope labeling with a more low-tech approach, such as the capillary feeder (CAFE). The CAFE assay, introduced by Ja in 2007, is similar to a water dispenser used for pet hamsters, but on a smaller scale.”In a significant number of studies, we found that researchers appeared indifferent to the impact feeding might have on the experiment,” Ja said. “This doesn’t seem like good science to me. Can you imagine doing a mouse experiment, saying that you watched mice for four hours and saw no difference in feeding, then make conclusions about total caloric intake over days or longer?”Story Source:The above story is based on materials provided by Scripps Research Institute. Note: Materials may be edited for content and length.

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Dropped your toast? Five-second food rule exists, new research suggests

Food picked up just a few seconds after being dropped is less likely to contain bacteria than if it is left for longer periods of time, according to the findings of research carried out at Aston University’s School of Life and Health Sciences.The findings suggest there may be some scientific basis to the ‘5 second rule’ — the urban myth about it being fine to eat food that has only had contact with the floor for five seconds or less. Although people have long followed the 5 second rule, until now it was unclear whether it actually helped.The study, undertaken by final year Biology students and led by Anthony Hilton, Professor of Microbiology at Aston University, monitored the transfer of the common bacteria Escherichia coli (E. coli) and Staphylococcus aureus from a variety of indoor floor types (carpet, laminate and tiled surfaces) to toast, pasta, biscuit and a sticky sweet when contact was made from 3 to 30 seconds.The results showed that:Time is a significant factor in the transfer of bacteria from a floor surface to a piece of food; and The type of flooring the food has been dropped on has an effect, with bacteria least likely to transfer from carpeted surfaces and most likely to transfer from laminate or tiled surfaces to moist foods making contact for more than 5 seconds. Professor Hilton said: “Consuming food dropped on the floor still carries an infection risk as it very much depends on which bacteria are present on the floor at the time; however the findings of this study will bring some light relief to those who have been employing the five-second rule for years, despite a general consensus that it is purely a myth. We have found evidence that transfer from indoor flooring surfaces is incredibly poor with carpet actually posing the lowest risk of bacterial transfer onto dropped food.The Aston team also carried out a survey of the number of people who employ the five-second rule. The survey showed that:87% of people surveyed said they would eat food dropped on the floor, or already have done so 55% of those that would, or have, eaten food dropped in the floor are women 81% of the women who would eat food from the floor would follow the 5 second rule Professor Hilton added: “Our study showed surprisingly that a large majority of people are happy to consume dropped food, with women the most likely to do so. But they are also more likely to follow the 5 second rule, which our research has shown to be much more than an old wives tail.”Story Source:The above story is based on materials provided by Aston University. Note: Materials may be edited for content and length.

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Fertilizer in small doses yields higher returns for less money

Crop yields in the fragile semi-arid areas of Zimbabwe have been declining over time due to a decline in soil fertility resulting from mono-cropping, lack of fertilizer, and other factors. In collaboration with the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT), University of Illinois researchers evaluated the use of a precision farming technique called “microdosing,” its effect on food security, and its ability to improve yield at a low cost to farmers.”Microdosing involves applying a small, affordable amount of fertilizer with the seed at planting time or as top dressing three to four weeks after emergence,” explained U of I agricultural economist Alex Winter-Nelson. “So, instead of spreading fertilizer over the entire field, microdosing uses fertilizer more efficiently and ultimately improves productivity. Our research shows that smallholder farmers’ investment in microdosing has really unlocked the power of chemical fertilizers in some of the low-rainfall areas of Zimbabwe.”Training is the key to adoption of the technique. “About 75 percent of households receiving microdosing training used fertilizer in 2011,” said Winter-Nelson. “This compares to less than 25 percent of households that had not received training. Another way of looking at it is that training in microdosing raised the probability of adoption by 30 to 35 percentage points. Knowledge of microdosing changed people’s attitudes about fertilizer. Those who had training generally disagreed with the common notion that fertilizer is not worth its price or that it burns crops.”Winter-Nelson said that there are some hurdles to overcome, however. “Sustaining and expanding the benefits of microdosing technology will require efforts to ensure that private agrodealers are able to stock the product in a timely manner and to package it in a manner that smallholder farmers find useful,” he said. …

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Soy and phytoestrogens, explained

Learn more about Herbalife – Follow @Herbalife on Twitter- Like Herbalife on Facebook- What is Herbalife? More fitness advice – Watch ‘Fit Tips’ Videos on YouTube- Straightforward exercise advice- Get fit = be happy. Positivity advice Nutrition advice for you – Watch ‘Healthy Living’ on YouTube- Dieting advice you might like- Interesting weight loss articles Copyright © 2013 Herbalife International of America, Inc.

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Discovery may help to explain mystery of ‘missing’ genetic risk, susceptibility to common diseases

A new study could help to answer an important riddle in our understanding of genetics: why research to look for the genetic causes of common diseases has failed to explain more than a fraction of the heritable risk of developing them.Susceptibility to common diseases is believed to arise through a combination of many common genetic variants that individually slightly increase the risk of disease, plus a smaller number of rare mutations that often carry far greater risk.However, even when their effects are added together, the genetic variants so far linked to common diseases account for only a relatively small proportion of the risk we know is conveyed by genetics through studies of family history.But the major new study, published in the journal PLOS Genetics, shows for the first time in cancer that some common genetic variants could actually be indicators of the presence of much more influential rare mutations that have yet to be found.Scientists at The Institute of Cancer Research, London, led an international consortium made up of more than 25 leading academic institutions on the study, which was funded by the European Union.The research, involving 20,440 men with prostate cancer and 21,469 without the disease, identified a cluster of four common genetic variants on chromosome 17 that appeared to give rise to a small increase in prostate cancer risk, using the standard statistical techniques for this type of study.But the study found an alternative explanation for the risk signal — a small proportion of the men with these common variants were in fact carriers of a rare mutation in the nearby HOXB13 gene, which is known to be linked to prostate cancer. Under this ‘synthetic association’, the number of people carrying a cancer risk variant was much lower than had been assumed, but those people who did inherit a variant had a much higher risk of prostate cancer than had been realised.The discovery shows that the prevailing genetic theory — that common cancers are predominantly caused by the combined action of many common genetic variants, each with only a very small effect — could potentially underestimate the impact of rare, as yet undiscovered mutations.The results are important because they show that there is a need for renewed effort by geneticists to find the causal variants, whether common or rare, behind the many common cancer-associated variants identified in recent years.Identifying any underlying rare mutations with a big effect on disease risk could improve the genetic screening and clinical management of individuals at greater risk of developing cancer, as well as other diseases.Study co-leader Dr Zsofia Kote-Jarai, Senior Staff Scientist at The Institute of Cancer Research (ICR), said: “As far as we are aware, this is the first known example of a ‘synthetic association’ in cancer genetics. It was exciting to find evidence for this theory, which predicts that common genetic variants that appear to increase risk of disease by only a modest amount may indeed sometimes be detected purely due to their correlation with a rarer variant which confers a greater risk.”Our study does not imply how widespread this phenomenon may be, but it holds some important lessons for geneticists in cancer, and other common diseases. It demonstrates the importance of identifying the causal genetic changes behind the many common variants that have already been shown to influence risk of disease.”Our study also demonstrates that standard methods to identify potential causal variants when fine-mapping genetic associations with disease may be inadequate to assess the contribution of rare variants. Large sequencing studies may be necessary to answer these questions unequivocally.”Study co-leader Professor Ros Eeles, Professor of Oncogenetics at The Institute of Cancer Research and Honorary Clinical Consultant at The Royal Marsden NHS Foundation Trust, said: “One important unanswered question in cancer genetics — and in genetics of common disease more generally — is why the genetic mutations we’ve discovered so far each seem to have such a small effect, when studies of families have shown that our genetic make-up has a very large influence on our risk of cancer.”Our study is an important step forward in our understanding of where we might find this ‘missing’ genetic risk in cancer. At least in part, it might lie in rarer mutations which current research tools have struggled to find, because individually each does not affect a large number of people.”

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Brain’s ‘sweet spot’ for love found in neurological patient

A region deep inside the brain controls how quickly people make decisions about love, according to new research at the University of Chicago.The finding, made in an examination of a 48-year-old man who suffered a stroke, provides the first causal clinical evidence that an area of the brain called the anterior insula “plays an instrumental role in love,” said UChicago neuroscientist Stephanie Cacioppo, lead author of the study.In an earlier paper that analyzed research on the topic, Cacioppo and colleagues defined love as “an intentional state for intense [and long-term] longing for union with another” while lust, or sexual desire, is characterized by an intentional state for a short-term, pleasurable goal.In this study, the patient made decisions normally about lust but showed slower reaction times when making decisions about love, in contrast to neurologically typical participants matched on age, gender and ethnicity. The findings are presented in a paper, “Selective Decision-Making Deficit in Love Following Damage to the Anterior Insula,” published in the journal Current Trends in Neurology.”This distinction has been interpreted to mean that desire is a relatively concrete representation of sensory experiences, while love is a more abstract representation of those experiences,” said Cacioppo, a research associate and assistant professor in psychology. The new data suggest that the posterior insula, which affects sensation and motor control, is implicated in feelings of lust or desire, while the anterior insula has a role in the more abstract representations involved in love.In the earlier paper, “The Common Neural Bases Between Sexual Desire and Love: A Multilevel Kernel Density fMRI Analysis,” Cacioppo and colleagues examined a number of studies of brain scans that looked at differences between love and lust.The studies showed consistently that the anterior insula was associated with love, and the posterior insula was associated with lust. However, as in all fMRI studies, the findings were correlational.”We reasoned that if the anterior insula was the origin of the love response, we would find evidence for that in brain scans of someone whose anterior insula was damaged,” she said.In the study, researchers examined a 48-year-old heterosexual male in Argentina, who had suffered a stroke that damaged the function of his anterior insula. He was matched with a control group of seven Argentinian heterosexual men of the same age who had healthy anterior insula.The patient and the control group were shown 40 photographs at random of attractive, young women dressed in appealing, short and long dresses and asked whether these women were objects of sexual desire or love. The patient with the damaged anterior insula showed a much slower response when asked if the women in the photos could be objects of love.”The current work makes it possible to disentangle love from other biological drives,” the authors wrote. Such studies also could help researchers examine feelings of love by studying neurological activity rather than subjective questionnaires.The full article can be found online at: https://hpenlaboratory.uchicago.edu/sites/caciopponeurolab.uchicago.edu/files/uploads/Cacioppo%20et%20al_Current%20Trends%20in%20Neurology%202013.pdfStory Source:The above story is based on materials provided by University of Chicago. Note: Materials may be edited for content and length.

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Urban bees using plastic to build hives

Once the snow melts, Canada’s bee population will be back in business — pollinating, making honey and keeping busy doing bee things. For at least two urban bee species, that means making nests out of plastic waste.A new study by a University of Guelph graduate and a U of G scientist reveals that some bees use bits of plastic bags and plastic building materials to construct their nests. The research was published recently in the journal Ecosphere.It’s an important discovery because it shows bees’ resourcefulness and flexibility in adapting to a human-dominated world, says lead author Scott MacIvor, a doctoral student at York University and a 2008 U of G graduate.”Plastic waste pervades the global landscape,” said MacIvor. Although researchers have shown adverse impacts of the material on species and the ecosystem, few scientists have observed insects adapting to a plastic-rich environment, he said.”We found two solitary bee species using plastic in place of natural nest building materials, which suggests innovative use of common urban materials.Figuring out that the bees were using plastics in place of natural materials took some detective work by U of G’s Andrew Moore, supervisor of analytical microscopy at Laboratory Services.Moore analyzed a grey “goo” that MacIvor discovered in the nests of one kind of bee, Megachile campanulae, which uses plant resins to build its nests,”Scott thought it might be chewing gum originally,” Moore said. His team uses a scanning electron microscope to take highly detailed pictures of items, x-ray microanalysis to determine the elements in the sample and infrared microscopy to identify polymers. They can distinguish the finest detail on the surface of an animal hair.Turns out that M. campanulae was occasionally replacing plant resins with polyurethane-based exterior building sealant, such as caulking, in its brood cells–created in a nest to rear larva.The researchers also discovered another kind of bee, Megachile rotundata, an alfalfa leafcutter, was using pieces of polyethylene-based plastic bags to construct its brood cells. The glossy plastic replaced almost one-quarter of the cut leaves normally used to build each cell.Markings showed that the bees chewed the plastic differently than they did leaves, suggesting that the insects had not incidentally collected plastic. Nor were leaves hard to find for the bees in the study.”The plastic materials had been gathered by the bees, and then worked — chewed up and spit out like gum — to form something new that they could use,” Moore said.In both cases, larvae successfully developed from the plastic-lined nests. In fact, the bees emerged parasite-free, suggesting plastic nests may physically impede parasites, the study said.The nests containing plastic were among more than 200 artificial nest boxes monitored by MacIvor as part of a large-scale investigation of the ecology of urban bees and wasps, a project involving numerous citizen scientists.The nest boxes are located in Toronto and the surrounding region in backyards, community gardens and parks and on green roofs. …

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Finnish agriculture increasingly steered by market forces

Agriculture in Finland is becoming more market driven in the next few years. EU and national support systems will continue to protect production, but the risks due to fluctuating prices will increase. MTT Agrifood Research Finland anticipates that the major structural changes in agriculture will continue, and the number of livestock farms in particular will decrease steadily.Last year, an agreement was reached on the common EU agricultural policy until 2020. The recent report by MTT Agrifood Research Finland describes the outlook of Finnish agriculture in the following five years.The market will take up the reinsThe agricultural production volumes in Finland on average will remain at the current level until 2020. Even though subsidies in nominal terms will remain in place to maintain production volumes, their real value will decrease. In order to maintain the income level, a larger part of the agricultural revenue than before must be gained from the products sold in the market.”The markets will increasingly influence what happens to the production, income and profitability in the agricultural sector. Prices will fluctuate wildly, which means that the market risks of agricultural enterprises increase both in the sale of products and the acquisition of production inputs,” says Professor Jyrki Niemi, MTT Agrifood Research Finland.For Finland, there will be no significant changes in the overall level of EU support to agriculture by 2020. “Since Finland’s northern circumstances were taken into account in the level of production-based support, the definition of less-favoured areas and the greening practices, the reform will not cause any dramatic changes in the Finnish agricultural market or production,” Niemi says.Precautions must be taken against production risksThe role of the state in the compensation of crop damages will change. After a transition period, crop damages will no longer be compensated directly from state funds. Instead, the state will participate in covering crop damages by creating prerequisites for commercial crop damage insurance.”The most important prerequisite for the creation of commercial insurance and insurance market is closing down the current system, which is completely funded by the state. …

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Mesothelioma Chemotherapy – 5 Commonly Asked Mesothelioma Chemotherapy Questions

Mesothelioma patients usually have some questions that they want answers for when they want to commence on Chemotherapy. These include:1. What is chemotherapy for mesothelioma? Chemotherapy involves one or more anti-cancer drugs taken either orally in pill form, or intravenously, or, in the case of pleural mesothelioma, injected directly into the lungs. These drugs inhibit the growth of cancerous cells, but they also damage normal healthy cells as well leading to the development of side effects.2. What are the common side effects of mesothelioma chemotherapy? Side effects are very common with the use of many Chemotherapy agents. The commonly seen side effects include:* hair loss * nausea * vomiting * diarrhea * constipation * anemia * hemorrhagingChemotherapy also causes many complicated side effects within the …

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Sinking teeth into the evolutionary origin of our skeleton

Oct. 16, 2013 — For decades, it was thought that our skeleton and all its characteristic bony tissues originated in the predators, known as ‘conodonts’. However new research, led by the University of Bristol and published today in Nature, shows that they were evolutionary copy-cats who evolved tooth-like structures and tissues independently of other vertebrates. The origin of our skeleton is to be found in the armour of our mud-slurping ancestors who evolved bony armour to protect themselves from such predators.Share This:Palaeontologists from Bristol, Peking University and the US Geological Survey collaborated with physicists from Switzerland to study the tooth-like skeleton of conodonts using high energy X-rays at the Swiss Light Source at the Paul Scherrer Institut in Switzerland. They showed that the tooth-like structures found in the mouths of conodonts evolved within their own evolutionary lineage, rather than in an ancestor shared with other vertebrates.Lead author, Duncan Murdock of the University of Bristol said: “We were able to visualise every tissue, cell and growth line within the bony teeth, allowing us to study their development. We compared the tooth-like skeleton of conodonts to that of their ‘paraconodont’ ancestors and to teeth in living vertebrates, demonstrating that the tooth-like structure of conodonts was assembled through evolutionary time independently of other vertebrates.”Co-author, Professor Philip Donoghue of the University of Bristol’s School of Earth Sciences said: “This removes a key piece of evidence from the hypothesis that teeth evolved before the skeletal armour, and suggests that the common ancestors of conodonts and other vertebrates likely lacked a mineralized skeleton. Rather, it seems that teeth evolved from the armour of our meek filter-feeding ancestors.”Share this story on Facebook, Twitter, and Google:Other social bookmarking and sharing tools:|Story Source: The above story is based on materials provided by University of Bristol. Note: Materials may be edited for content and length. For further information, please contact the source cited above. Journal Reference:Duncan J. …

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Mesothelioma Lawyers – Three Crucial Questions You Must Ask Your Lawyer

After receiving a diagnosis of mesothelioma you have to look for a reputable and qualified mesothelioma Lawyer to litigate your case for you. As a mesothelioma victim you are entitled to receiving substantial monetary compensation from the company that probably exposed you to the harmful effects of asbestos fibers which led to your development of the cancer.Choosing your mesothelioma lawyer can be daunting task, you just have to choose right or else you stand the chance of loosing out on getting the compensation you deserve. Your Lawyer will determine whether or not you are successful in your mesothelioma LawsuitBefore you make up your mind on your choice of Lawyer you have to set up a meeting with your prospective Lawyers and make sure you ask them …

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Dr. David Nutt on Alcohol

Rebutting industry myths.A couple of years ago, the European Alcohol Policy Alliance, known as EuroCare, put together a brochure addressing the common messages the liquor industry attempts to drive home through its heavy spending on advertising. The messages are not just designed to sell product, but also to influence alcohol policy at the political level. According to EuroCare, the “industry”—the alcohol and tobacco companies—“has traditionally worked closely together, sharing information and concerns about regulation. They have used similar arguments to defend their products in order to prevent or delay restrictions being placed on them.”I wrote a blog post on EuroCare’s list of alcohol untruths called “7 Myths the Alcohol Industry Wants You to Believe.” Here they are:Message 1: Consuming alcohol is normal, common, healthy, …

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New approach urged for ‘abysmal’ K-12 writing instruction

Oct. 11, 2013 — Writing instruction in U.S. classrooms is “abysmal” and the Common Core State Standards don’t go far enough to address glaring gaps for students and teachers, a Michigan State University education scholar argues.In a new study, Gary Troia calls for a fresh approach to professional development for teachers who must help students meet the new writing standards. His research, funded by the U.S. Department of Education’s Institute of Education Sciences, appears in the journal School Psychology Review.”We need to re-orient the way we think about teacher professional development,” said Troia, associate professor in MSU’s College of Education. “We need to be smarter about professional development and make sure it’s comprehensive, sustained and focused on the needs in the classroom.”The Common Core standards aim to improve U.S. student performance in mathematics and English language arts, which include writing. The standards have been adopted by 45 states and are in various phases of being rolled out for implementation.While the standards are strong in some areas of writing instruction, they are weak in many others, Troia said. For example, spelling and handwriting are not addressed comprehensively in early grades. Keyboarding is a focus only in grades 3 through 6, even though computers have become increasingly important throughout school and new assessments aligned with the Common Core will use computers. …

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Turning to parasites as potential disease fighters

Sep. 9, 2013 — There is a new weapon in the fight against autoimmune diseases such as Type 1 diabetes, rheumatoid arthritis, Crohn’s disease and lupus, the common trait of which is an immune system that attacks its own organs and tissues.William Gause, an immunologist at Rutgers New Jersey Medical School, is among those leading the charge against these diseases by studying how the human body reacts to worms. The worms Gause studies, or helminths as biologists call them, are small parasites that live in human intestines, especially in the developing world.According to an article in Nature Reviews Immunology by Gause and colleagues from the National Institutes of Health and the University of Edinburgh, the worms’ presence through millennia of human evolution likely has led to an immune response called type 2 immunity. This includes immune regulatory pathways that help control the inflammation that can contribute to autoimmune diseases.The immune reaction, the researchers say, appears to have developed as a way to rapidly repair wounds caused by these invaders as they move through the body. In fact, components of the type 2 immune response may someday be used to enhance the wound healing process. Additionally, this response triggers regulatory networks that block harmful immune responses, or inflammation, that otherwise would exacerbate the tissue injury.”What we would like to do now is harness components of the type 2 immune response to target the control of harmful inflammation that can lead to autoimmune diseases like diabetes and inflammatory bowel disease,” Gause says. He adds that inflammatory responses also have been linked to other diseases, including cardiovascular disease and metabolic disorders, and even to allergic reactions and fibrosis that may result when titanium shavings that flake away from artificial joints settle in the body. “Finding new ways to stimulate these regulatory components of the type 2 immune response may provide us with a new set of tools to target the control of harmful inflammatory responses now associated with this wide array of different diseases.”For now, live helminths or helminth byproducts may be introduced into the body on a short-term basis to train compromised immune systems. A 2012 study by a Gause-led team found that the introduction of helminths for two weeks caused the immune systems of mice to produce cytokines, or signaling molecules, which gave them lasting protection against Type 1 diabetes.That finding mirrors human experience in the developing world where helminth infection is endemic, but the incidence of autoimmune diseases such as Type 1 diabetes is extremely low.”There is a growing body of evidence to support the hygiene hypothesis, which suggests that decreased exposure to microbes and helminths in industrialized countries may impair the development of immune regulatory networks that would otherwise control harmful inflammatory responses,” Gause says.The end result of that process, according to Gause, is increased incidence of a variety of diseases linked to harmful inflammation. “If we find a controlled way to apply the benefit that helminths appear to provide to the workings of the immune system, it is conceivable that we as a society would no longer need to endure the apparent tradeoff between clean living conditions and inflammatory diseases.”

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Mutations in a gene that impacts immune function increase susceptibility to prostate cancer

Aug. 29, 2013 — A team of researchers led by Janet Stanford, Ph.D., of Fred Hutchinson Cancer Research Center has discovered that mutations in the gene BTNL2, which encodes a protein involved in regulating T-cell proliferation and cytokine production — both of which impact immune function — increase the risk of developing prostate cancer.The findings, by Stanford and colleagues from the University of Washington Genome Sciences Department and the National Human Genome Research Institute, are online ahead of the print issue of Cancer Epidemiology, Biomarkers & Prevention.A complex disease with a strong genetic componentProstate cancer is a complex disease and its causes include a strong genetic component. It is estimated that about 42 percent of prostate cancer cases are due to heredity, or genetic variations present at birth. Five to 10 percent of those prostate cancer cases are thought to result from rare inherited mutations.The researchers studied multiple prostate cancer patients from families with a pattern of hereditary prostate cancer, or HPC. Germline DNA provided by patients with more aggressive or early onset disease was sequenced in an attempt to identify rare genetic mutations that predispose to prostate cancer. All the participants were men of European ancestry.Several genes with candidate mutations were highlighted, but two coding variants in the butyrophilin-like 2, or BTNL2, gene were most strongly related to the development of prostate cancer. These missense mutations that change the genetic code were subsequently confirmed to be clearly associated with prostate cancer in an independent set of HPC families and in a case-control study population.The team found that the two BTNL2 mutations associated with elevated prostate cancer risk are rare. In the 270 HPC families used for confirmation, about 1.5 percent of affected men carried one of the mutations but unaffected men carried none. In the population-based case-control study, 2 percent of prostate cancer cases and less than 1 percent of men without prostate cancer carried one of the variants.Mutations increased risk of both hereditary and sporadic prostate cancerIn the case-control study, men who carried one of these variants had a significant 2.5- to 2.7-fold higher risk for developing prostate cancer compared to men who did not carry either mutation.”This research demonstrates for the first time that rare mutations in the BTNL2 gene enhance susceptibility to both hereditary and sporadic prostate cancer,” said Stanford, co-director of the Program in Prostate Cancer Research a member of the Public Health Sciences Division at Fred Hutch. Common variants in this gene have been previously linked to several autoimmune and inflammatory diseases such as sarcoidosis and ulcerative colitis.The researchers used a next-generation sequencing technology called whole-exome sequencing, which consists of sequencing all the coding regions, called exons, across the genome. …

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Zealous imaging fuelling unnecessary and harmful treatment of low risk thyroid cancers, experts warn

Aug. 27, 2013 — New imaging techniques are fuelling an epidemic in diagnosis and treatment of thyroid cancers that are unlikely to ever progress to cause symptoms or death, warn experts on bmj.com today.New technologies such as ultrasound, CT and MRI scanning can detect thyroid nodules as small as 2mm — many of these small nodules are papillary thyroid cancers.In the US, cases have tripled in the past 30 years — from 3.6 per 100,000 in 1973 to 11.6 per 100,000 in 2009 — making it one of the fastest growing diagnoses. Yet the death rate from papillary thyroid cancer has remained stable.This expanding gap between incidence of thyroid cancer and deaths suggests that low risk cancers are being overdiagnosed and overtreated, argue Dr Juan Brito and colleagues at the Mayo Clinic in Minnesota.This is exposing patients to unnecessary and harmful treatment that is inconsistent with their prognosis, they warn, and they say both the overdiagnosis and overtreatment of this form of cancer need to be fully recognised.The article is part of a series looking at the risks and harms of overdiagnosis in a range of common conditions. The series, together with the Preventing Overdiagnosis conference in September, are part of the BMJ’s Too Much Medicine campaign to help tackle the threat to health and the waste of money caused by unnecessary care.The authors say that unnecessary thyroidectomy (the surgical removal of all or part of the thyroid gland) is costly and carries a risk of complications such as low calcium levels and nerve injury. In the US, the number of thyroidectomies for thyroid cancer has risen by 60% over the past 10 years at an estimated cost of $416m (£270m; €316m).Using radioactive iodine in patients with low risk thyroid cancer has also increased from one in 300 patients to two in five patients between 1973 and 2006, despite recommendations against using it, they add.They acknowledge that inferring overdiagnosis of thyroid cancer has limitations, but say that uncertainty about the benefits and harms of immediate treatment for low risk papillary thyroid cancer “should spur clinicians to engage patients in shared decision making … to ensure treatment is consistent with the research evidence and patient goals.”They suggest a term that conveys favorable prognosis for low risk thyroid cancers (microPapillary Lesions of Indolent Course or microPLIC)) and makes it easier to give patients the choice of active surveillance over immediate and often intensive treatment. And they call for research to identify the appropriate care for these patients.

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Tumors form advance teams to ready lungs for spread of cancer

Aug. 16, 2013 — Cancer metastasis requires tumor cells to acquire properties that allow them to escape from the primary tumor site, travel to a distant place in the body, and form secondary tumors. But first, an advance team of molecules produced by the primary tumor sets off a series of events that create a network of nurturing blood vessels for arriving primary tumor cells to set up shop.In lung cancer, the formation of that niche likely involves immune cells and moderate levels of VEGF and other molecules that promote the formation of new blood vessels, or angiogenesis. But little is known about how the local lining, or endothelial, cells are activated at the niche.Sandra Ryeom, PhD, assistant professor of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, and colleagues, found that the signaling protein calcineurin upregulates another molecule, Ang-2 that promotes the needed angiogenesis. Hyperactivation of calcineurin in genetically altered mice that lack an inhibitior of calcineurin signaling leads to increased lung metastases. Conversely, inhibiting calcineurin or Ang-2 blocked metastases in lung cells of the mice. The findings are published this week in Cell Reports.The findings may help shed light on the underpinnings of common cancer metastasis patterns, such as the tendency of prostate cancer to spread to the bones, or melanoma to the brain.”We demonstrated that the calcineurin pathway is activated specifically in lung endothelium prior to the detection of tumor cells that preferentially and spontaneously metastasize to the lung from our experimental model of flank tumors in mice,” says Ryeom.Also, increased VEGF levels specifically in the lung, and not other organ microenvironments, trigger a threshold amount of calcineurin signaling that activates the Ang2 gene in lung endothelial cells. What’s more, they showed that overexpression of the Ang-2 receptor prevents activation of the lung endothelium and inhibits lung metastases in their mouse models. “Our studies provide insights into the mechanisms underlying angiogenesis in the pre-metastatic niche and offer new targets for lung metastases,” she says. Because calcineurin acts on the pathways that set up sites of metastasis away from the primary tumor sites, it could be a potential target for future cancer therapies; however it is also active in the immune system. …

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Populations of grassland butterflies decline almost 50 percent over two decades: European report

July 23, 2013 — Grassland butterflies have declined dramatically between 1990 and 2011. This has been caused by intensifying agriculture and a failure to properly manage grassland ecosystems, according to a report from the European Environment Agency (EEA).In the report the data of the Butterfly monitoring scheme in Germany have been incorporated, which is scientifically supported by the Helmholtz Centre for Environmental Research (UFZ). UFZ scientists have also contributed to the analysis of population trends.The fall in grassland butterfly numbers is particularly worrying, according to the report, because these butterflies are considered to be representative indicators of trends observed for most other terrestrial insects, which together form around two thirds of the world’s species. This means that butterflies are useful indicators of biodiversity and the general health of ecosystems.Seventeen butterfly species are examined in ‘The European Grassland Butterfly Indicator: 1990-2011’, comprising seven widespread and 10 specialist species. Of the 17 species, eight have declined in Europe, two have remained stable and one increased. For six species the trend is uncertain.Butterflies examined in the report include the Common Blue (Polyommatus icarus), which has declined significantly, the Orangetip (Anthocharis cardamines), which seems to be stable since 1990, and the Lulworth Skipper (Thymelicus acteon), which shows an uncertain trend over the last two decades.Hans Bruyninckx, EEA Executive Director, said: “This dramatic decline in grassland butterflies should ring alarm bells — in general Europe’s grassland habitats are shrinking. If we fail to maintain these habitats we could lose many of these species forever. We must recognise the importance of butterflies and other insects — the pollination they carry out is essential for both natural ecosystems and agriculture.”Why are butterflies disappearing?Intensifying agriculture and abandoned land are the two main trends affecting the populations of grassland butterflies. Agriculture has intensified where the land is relatively flat and easy to cultivate, and, on the other hand,large areas of grasslands have been abandoned in mountainous and wet regions, mainly in eastern and southern Europe. Both intensification and abandonment result in the loss and degradation of habitat for grassland butterflies.Agricultural intensification leads to uniform grasslands which are almost sterile for biodiversity. …

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Key molecular pathways leading to Alzheimer’s identified

July 24, 2013 — Key molecular pathways that ultimately lead to late-onset Alzheimer’s disease, the most common form of the disorder, have been identified by researchers at Columbia University Medical Center (CUMC). The study, which used a combination of systems biology and cell biology tools, presents a new approach to Alzheimer’s disease research and highlights several new potential drug targets. The paper was published today in the journal Nature.Much of what is known about Alzheimer’s comes from laboratory studies of rare, early-onset, familial (inherited) forms of the disease. “Such studies have provided important clues as to the underlying disease process, but it’s unclear how these rare familial forms of Alzheimer’s relate to the common form of the disease,” said study leader Asa Abeliovich, MD, PhD, associate professor of pathology and cell biology and of neurology in the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain at CUMC. “Most important, dozens of drugs that ‘work’ in mouse models of familial disease have ultimately failed when tested in patients with late-onset Alzheimer’s. This has driven us, and other laboratories, to pursue mechanisms of the common form of the disease.”Non-familial Alzheimer’s is complex; it is thought to be caused by a combination of genetic and environmental risk factors, each having a modest effect individually. Using so-called genome-wide association studies (GWAS), prior reports have identified a handful of common genetic variants that increase the likelihood of Alzheimer’s. A key goal has been to understand how such common genetic variants function to impact the likelihood of Alzheimer’s.In the current study, the CUMC researchers identified key molecular pathways that link such genetic risk factors to Alzheimer’s disease. The work combined cell biology studies with systems biology tools, which are based on computational analysis of the complex network of changes in the expression of genes in the at-risk human brain.More specifically, the researchers first focused on the single most significant genetic factor that puts people at high risk for Alzheimer’s, called APOE4 (found in about a third of all individuals). People with one copy of this genetic variant have a three-fold increased risk of developing late-onset Alzheimer’s, while those with two copies have a ten-fold increased risk. …

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