Pittwater Online News

 New device allows brain to bypass spinal cord, move paralysed limbs

June 25, 2014 – For the first time ever, a paralysed man can move his fingers and hand with his own thoughts thanks to an innovative partnership between The Ohio State University Wexner Medical Center and Battelle. Ian Burkhart, a 23-year-old quadriplegic from Dublin, Ohio, is the first patient to use Neurobridge, an electronic neural bypass for spinal cord injuries that reconnects the brain directly to muscles, allowing voluntary and functional control of a paralyzed limb. Burkhart is the first of a potential five participants in a clinical study.

"It's much like a heart bypass, but instead of bypassing blood, we're actually bypassing electrical signals," said Chad Bouton, research leader at Battelle. "We're taking those signals from the brain, going around the injury, and actually going directly to the muscles."

The Neurobridge technology combines algorithms that learn and decode the user's brain activity and a high-definition muscle stimulation sleeve that translates neural impulses from the brain and transmits new signals to the paralyzed limb. In this case, Ian's brain signals bypass his injured spinal cord and move his hand, hence the name Neurobridge.

Burkhart, who was paralyzed four years ago during a diving accident, viewed the opportunity to participate in the six-month, FDA-approved clinical trial at Ohio State's Wexner Medical Center as a chance to help others with spinal cord injuries.

"Initially, it piqued my interested because I like science, and it's pretty interesting," Burkhart said. "I've realized, 'You know what? This is the way it is. You're going to have to make the best out of it.' You can sit and complain about it, but that's not going to help you at all. So, you might as well work hard, do what you can and keep going on with life."

This technology has been a long time in the making. Working on the internally-funded project for nearly a decade to develop the algorithms, software and stimulation sleeve, Battelle scientists first recorded neural impulses from an electrode array implanted in a paralyzed person's brain. They used that data to illustrate the device's effect on the patient and prove the concept.

Two years ago, Bouton and his team began collaborating with Ohio State neuroscience researchers and clinicians Dr. Ali Rezai and Dr. Jerry Mysiwto design the clinical trials and validate the feasibility of using the Neurobridge technology in patients.

During a three-hour surgery on April 22, Rezai implanted a chip smaller than a pea onto the motor cortex of Burkhart's brain. The tiny chip interprets brain signals and sends them to a computer, which recodes and sends them to the high-definition electrode stimulation sleeve that stimulates the proper muscles to execute his desired movements. Within a tenth of a second, Burkhart's thoughts are translated into action.

"The surgery required the precise implantation of the micro-chip sensor in the area of Ian's brain that controls his arm and hand movements," Rezai said.

He said this technology may one day help patients affected by various brain and spinal cord injuries such as strokes and traumatic brain injury.

Battelle also developed a non-invasive neurostimulation technology in the form of a wearable sleeve that allows for precise activation of small muscle segments in the arm to enable individual finger movement, along with software that forms a 'virtual spinal cord' to allow for coordination of dynamic hand and wrist movements.

The Ohio State and Battelle teams worked together to figure out the correct sequence of electrodes to stimulate to allow Burkhart to move his fingers and hand functionally. For example, Burkhart uses different brain signals and muscles to rotate his hand, make a fist or pinch his fingers together to grasp an object, Mysiw said. As part of the study, Burkhart worked for months using the electrode sleeve to stimulate his forearm to rebuild his atrophied muscles so they would be more responsive to the electric stimulation.

"I've been doing rehabilitation for a lot of years, and this is a tremendous stride forward in what we can offer these people," said Mysiw, chair of the Department of Physical Medicine and Rehabilitation at Ohio State. "Now we're examining human-machine interfaces and interactions, and how that type of technology can help."

Burkhart is hopeful for his future.

"It's definitely great for me to be as young as I am when I was injured because the advancements in science and technology are growing rapidly and they're only going to continue to increase."

The above story is based on materials provided by Ohio State University, Wexner Medical Center.

Health papers published this week:

Nutritional sports supplements sold in Australia test positive for banned androgens

June 23, 2014 – Some nutritional sports supplements marketed to athletes - claiming to help them build lean muscle, reduce body fat and enhance endurance - are secretly fortified with androgens, which are banned from use in sports, a new study from Australia finds. The results will be presented in a poster Sunday, June 22, at ICE/ENDO 2014, the joint meeting of the International Society of Endocrinology and the Endocrine Society in Chicago.

"The point is that 'you can't judge a book by its cover.' The nutritional supplement label may not disclose all ingredients, and sometimes these additions are not declared on the product label. Athletes risk testing positive for a banned substance and the general public risks being inadvertently exposed to androgens, which have recognized health risks," said principal investigator Alison Heather, PhD, professor in the Department of Physiology of the School of Medical Sciences at the University of Otago in Dunedin, New Zealand.

"The presence of androgens in the supplements is concerning, given that the products do not declare their addition. We need to investigate further just what the androgens in these supplements are so we can better understand the implications for health and sports doping," she said.

The worldwide dietary supplement market is worth an estimated $142.1 billion and by 2017 is expected to reach $204.8 billion, and most androgen-containing supplements state their contents on the label. Yet, the scientific literature contains reports of unlabeled androgen-containing supplements, and lacking good manufacturing practice and regulation, companies can covertly add androgens to their nutritional supplements to better satisfy their advertised claims.

To investigate the availability of unlisted androgens in over-the-counter nutritional sports supplements, Professor Heather and her co-authors purchased 79 nutritional supplements randomly from Sydney-based stores, including protein powders, amino acids, creatines, fat metabolizers, "testosterone-boosters," carbohydrates and stimulant/nitric oxide "pre-workout"-based supplements.

Of the 74 samples they tested by bioassay, 6 were androgen-positive but did not list them on the label, and 1 was positive but listed an androgen on the label.

Professor Heather cautioned that, although only 10% of their supplements tested positive for androgens, the nutritional sports supplement industry is not very transparent about revealing all the ingredients in their products. She recommended more stringent legislation to enable the public to be fully aware of what they are putting into their bodies.

The above story is based on materials provided by Endocrine Society.

Young women with polycystic ovary syndrome are 5 times more likely to develop type 2 diabetes

June 24, 2014 – A leading expert on reproductive health says young women with Polycystic Ovary Syndrome (PCOS) have a startlingly higher risk of developing type 2 diabetes, even if young and not overweight. The research led by Professor Helena Teede and Dr Anju Joham, from the School of Public Health and Preventive Medicine at Monash University analysed a large-scale epidemiological study, called the Australian Longitudinal Study of Women's Health, which revealed the findings.

Over 6000 women aged between 25-28 years were monitored for nine years, including 500 with diagnosed PCOS. The incidence and prevalence of type 2 diabetes was three to five times higher in women with PCOS. Crucially, obesity, a key trigger for type 2 diabetes, was not an important trigger in women with PCOS.

Professor Teede said the findings have significant implications for diabetes screening, as well as for the care of women with PCOS.

"Type 2 diabetes itself is preventable, as are diabetes complications, but only if people at risk of or who have diabetes are screened, aware and take preventative action," Professor Teede said.

"With the dramatic rise in diabetes, this research highlights the need for greater awareness and screening, especially in high risk groups including young women with PCOS."

The women studied were aged 25-28 in 2003 and were followed over 9 years until age 34 to 37 years in 2012.

Professor Teede said these are the peak reproductive years when undiagnosed diabetes could have significant risks for mothers and babies.

"Our research found that there is a clear link between PCOS and diabetes. However, PCOS is not a well-recognised diabetes risk factor and many young women with the condition don't get regular diabetes screening even pre pregnancy, despite recommendations from the Australian PCOS evidence based guidelines." She said.

"Currently diabetes screening guidelines recommend screening over 40 years of age. This may need to be reconsidered in women with PCOS. We clearly need more research in PCOS, with better screening, prevention and treatments."

Affecting around 1 in 5 women, the study also shows that many women with PCOS remain undiagnosed with what is the most common hormonal disorder in women. Symptoms can include irregular periods, weight gain, excessive facial hair and acne. PCOS is commonly managed with regular screening and prevention strategies, alongside lifestyle changes and medication.

The above story is based on materials provided by Monash University. 

Battle of the bulge occurs in the liver

June 23, 2014 - An international team of scientists led by Monash University researchers has shown how free radicals contribute to type 2 diabetes, obesity and fatty liver disease.

Type 2 diabetes and non-alcoholic fatty liver disease are key complications of obesity as 80 per cent of patients with type 2 diabetes are obese, and 75 per cent of patients who are obese or have type 2 diabetes also have fatty liver disease.

The team, led by Professor Tony Tiganis from the Department of Biochemistry and Molecular Biology at Monash, has found that free radical molecules called Reactive Oxygen Species (ROS) wage a battle with enzymes called protein tyrosine phosphatases, initiating a cascade of events with devastating consequences.

The findings, published in the journal Cell Metabolism, explain how selective insulin resistance - a pathological feature of type 2 diabetes - occurs in the liver. The study identifies the molecular culprits involved, and reveals how they contribute to disease progression.

"We have shown for the very first time that these free radicals inactivate protein tyrosine phosphatases in the liver to activate rogue pathways that promote fatty liver disease and exacerbate the development of obesity and type 2 diabetes," Professor Tiganis said.

Professor Tiganis' team found in lab studies that obesity promoted ROS generation that inactivated a phosphatase called PTPN2. This inactivation in turn exacerbated obesity and fatty liver disease progression.

While there is more work to be done to understand the causes of fatty liver disease, Professor Tiganis has plans to test two potential therapeutic approaches. One involves inactivating a protein in the liver, and the other will use a selective anti-oxidant to 'mop up' excess free radicals that would otherwise inactivate PTPN2.

While free radicals play important roles in disease, Professor Tiganis advises against taking anti-oxidants indiscriminately.

"Although we need to undertake further studies in humans, preclinical studies indicate that ROS also play important roles in biology," he said.

Esteban N. Gurzov, Melanie Tran, Manuel A. Fernandez-Rojo, Troy L. Merry, Xinmei Zhang, Yang Xu, Atsushi Fukushima, Michael J. Waters, Matthew J. Watt, Sofianos Andrikopoulos, Benjamin G. Neel, Tony Tiganis. Hepatic Oxidative Stress Promotes Insulin-STAT-5 Signaling and Obesity by Inactivating Protein Tyrosine Phosphatase N2. Cell Metabolism, 2014; DOI:10.1016/j.cmet.2014.05.011

Sharpening a test for tracing food-borne illness to source

June 23, 2014 – Research from the University of Melbourne, Australia, could make it easier for public health investigators to determine if a case of food poisoning is an isolated incident or part of a larger outbreak. The findings are published ahead of print in the Journal of Bacteriology. The study focuses on a test called multi-locus variable number tandem repeats variable analysis (MLVA). The test, which is increasingly used in the detection and investigation of foodborne outbreaks, analyzes specific sequences of DNA (called loci) that change rapidly enough over time to distinguish outbreak strains from other circulating strains of the bacteria but not so rapidly that connections could be masked by changes arising during the course of an outbreak.

However, the rates at which MLVA profiles change have not been directly investigated for Salmonella, and thus it is sometimes unclear how these profiles should be interpreted in the context of outbreak detection and investigation.

In the study, the investigators grew an isolate ofSalmonella Typhimurium from an Australian food poisoning outbreak, and observed changes in its MLVA profile during more than 28,000 generations of growth in the laboratory. Then, using the same bacterial lineage, they observed changes in MLVA profile during 500 days of growth in mice.

They estimated the rates of copy number change at each of the five loci that are commonly used for S. Typhimurium MLVA. Three of the loci saw changes in the DNA, but two did not. Based on these results, the researchers are recommending that isolates with zero or one variation in the three rapidly changing loci but no differences in the other two should be considered part of the same cluster.

They also noted that the relative rates of change among the loci were the same in the Petri dish studies and in the mouse study.

"This tells us we don't need to worry about where the bacteria were isolated from - humans or food," says Kathryn Holt, an author on the study.

MLVA is used for investigations of food-borne illnesses besides Salmonella, including Listeria, and E. coli. It is the primary method for investigations of Salmonella outbreaks in Europe, the UK, Australia, and elsewhere, says Holt.

"In the U.S., the Centers for Disease Control and Prevention uses another technique called PFGE for initial investigations and follows that with MLVA," she says.

Kathryn Holt et al. Analysis of Salmonella Typhimurium variable number tandem repeat (VNTR) data for public health investigation based on measured mutation rates and whole-genome sequence comparisons.Journal of Bacteriology, June 2014 DOI: 10.1128/JB.01820-14

Schizophrenia and cannabis use may share common genes

June 24, 2014 - Genes that increase the risk of developing schizophrenia may also increase the likelihood of using cannabis, according to a new study led by King's College London, published today in Molecular Psychiatry.

Previous studies have identified a link between cannabis use and schizophrenia, but it has remained unclear whether this association is due to cannabis directly increasing the risk of the disorder.

The new results suggest that part of this association is due to common genes, but do not rule out a causal relationship between cannabis use and schizophrenia risk.

Mr Robert Power, lead author from the MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre at the Institute of Psychiatry at King's, says: "Studies have consistently shown a link between cannabis use and schizophrenia. We wanted to explore whether this is because of a direct cause and effect, or whether there may be shared genes which predispose individuals to both cannabis use and schizophrenia."

Cannabis is the most widely used illicit drug in the world, and its use is higher amongst people with schizophrenia than in the general population. Schizophrenia affects approximately 1 in 100 people and people who use cannabis are about twice as likely to develop the disorder. The most common symptoms of schizophrenia are delusions (false beliefs) and auditory hallucinations (hearing voices). Whilst the exact cause is unknown, a combination of physical, genetic, psychological and environmental factors can make people more likely to develop the disorder.

Previous studies have identified a number of genetic risk variants associated with schizophrenia, each of these slightly increasing an individual's risk of developing the disorder.

The new study included 2,082 healthy individuals of whom 1,011 had used cannabis. Each individual's 'genetic risk profile' was measured - that is, the number of genes related to schizophrenia each individual carried.

The researchers found that people genetically pre-disposed to schizophrenia were more likely to use cannabis, and use it in greater quantities than those who did not possess schizophrenia risk genes.

Power says: "We know that cannabis increases the risk of schizophrenia. Our study certainly does not rule this out, but it suggests that there is likely to be an association in the other direction as well - that a pre-disposition to schizophrenia also increases your likelihood of cannabis use."

"Our study highlights the complex interactions between genes and environments when we talk about cannabis as a risk factor for schizophrenia. Certain environmental risks, such as cannabis use, may be more likely given an individual's innate behaviour and personality, itself influenced by their genetic make-up. This is an important finding to consider when calculating the economic and health impact of cannabis."

The study is a collaboration between King's and the Queensland Institute of Medical Research in Australia, partly funded by the UK Medical Research Council (MRC). Additional funding was provided by the National Institutes of Health, Australian National health and Medical Research Council, Australian Research Council, GenomEUtwin Project, Centre for Research Excellence on Suicide Prevention in Australia, the National Institute for Health Research Biomedical Research Centre (NIHR BRC) at the South London and Maudsley NHS Foundation Trust and King's College London and the Netherlands Organization for Health Research and Development.

R A Power, K J H Verweij, M Zuhair, G W Montgomery, A K Henders, A C Heath, P A F Madden, S E Medland, N R Wray, N G Martin. Genetic predisposition to schizophrenia associated with increased use of cannabis. Molecular Psychiatry, 2014; DOI: 10.1038/mp.2014.51

First demonstration of a self-powered cardiac pacemaker

June 23, 2014 - A research team from the Korea Advanced Institute of Science and Technology (KAIST), headed by Professor Keon Jae Lee of the Department of Materials Science and Engineering at KAIST and Professor Boyoung Joung, M.D. of the Division of Cardiology at Severance Hospital of Yonsei University, has developed a self-powered artificial cardiac pacemaker that is operated semi-permanently by a flexible piezoelectric nanogenerator.

The artificial cardiac pacemaker is widely acknowledged as medical equipment that is integrated into the human body to regulate the heartbeats through electrical stimulation to contract the cardiac muscles of people who suffer from arrhythmia. However, repeated surgeries to replace pacemaker batteries have exposed elderly patients to health risks such as infections or severe bleeding during operations.

The team's newly designed flexible piezoelectric nanogenerator directly stimulated a living rat's heart using electrical energy converted from the small body movements of the rat. This technology could facilitate the use of self-powered flexible energy harvesters, not only prolonging the lifetime of cardiac pacemakers but also realizing real-time heart monitoring.

The research team fabricated high-performance flexible nanogenerators utilizing a bulk single-crystal PMN-PT thin film (iBULe Photonics). The harvested energy reached up to 8.2 V and 0.22 mA by bending and pushing motions, which were high enough values to directly stimulate the rat's heart.

Professor Keon Jae Lee said:

"For clinical purposes, the current achievement will benefit the development of self-powered cardiac pacemakers as well as prevent heart attacks via the real-time diagnosis of heart arrhythmia. In addition, the flexible piezoelectric nanogenerator could also be utilized as an electrical source for various implantable medical devices."

Geon-Tae Hwang, Hyewon Park, Jeong-Ho Lee, SeKwon Oh, Kwi-Il Park, Myunghwan Byun, Hyelim Park, Gun Ahn, Chang Kyu Jeong, Kwangsoo No, HyukSang Kwon, Sang-Goo Lee, Boyoung Joung, Keon Jae Lee. Self-Powered Cardiac Pacemaker Enabled by Flexible Single Crystalline PMN-PT Piezoelectric Energy Harvester. Advanced Materials, 2014; DOI:10.1002/adma.201400562

Association found between maternal exposure to agricultural pesticides and autism

June 23, 2014 - Pregnant women who lived in close proximity to fields and farms where chemical pesticides were applied experienced a two-thirds increased risk of having a child with autism spectrum disorder or other developmental delay, a study by researchers with the UC Davis MIND Institute has found. The associations were stronger when the exposures occurred during the second and third trimesters of the women's pregnancies.

The large, multisite California-based study examined associations between specific classes of pesticides, including organophosphates, pyrethroids and carbamates, applied during the study participants' pregnancies and later diagnoses of autism and developmental delay in their offspring. It is published online in Environmental Health Perspectives.

"This study validates the results of earlier research that has reported associations between having a child with autism and prenatal exposure to agricultural chemicals in California," said lead study author Janie F. Shelton, a UC Davis graduate student who now consults with the United Nations. "While we still must investigate whether certain sub-groups are more vulnerable to exposures to these compounds than others, the message is very clear: Women who are pregnant should take special care to avoid contact with agricultural chemicals whenever possible."

California is the top agricultural producing state in the nation, grossing $38 billion in revenue from farm crops in 2010. Statewide, approximately 200 million pounds of active pesticides are applied each year, most of it in the Central Valley, north to the Sacramento Valley and south to the Imperial Valley on the California-Mexico border. While pesticides are critical for the modern agriculture industry, certain commonly used pesticides are neurotoxic and may pose threats to brain development during gestation, potentially resulting in developmental delay or autism.

The study was conducted by examining commercial pesticide application using the California Pesticide Use Report and linking the data to the residential addresses of approximately 1,000 participants in the Northern California-based Childhood Risk of Autism from Genetics and the Environment (CHARGE) Study. The study includes families with children between 2 and 5 diagnosed with autism or developmental delay or with typical development. It is led by principal investigator Irva Hertz-Picciotto, a MIND Institute researcher and professor and vice chair of the Department of Public Health Sciences at UC Davis. The majority of study participants live in the Sacramento Valley, Central Valley and the greater San Francisco Bay Area.

Twenty-one chemical compounds were identified in the organophosphate class, including chlorpyrifos, acephate and diazinon. The second most commonly applied class of pesticides was pyrethroids, one quarter of which was esfenvalerate, followed by lambda-cyhalothrin permethrin, cypermethrin and tau-fluvalinate. Eighty percent of the carbamates were methomyl and carbaryl.

For the study, researchers used questionnaires to obtain study participants' residential addresses during the pre-conception and pregnancy periods. The addresses then were overlaid on maps with the locations of agricultural chemical application sites based on the pesticide-use reports to determine residential proximity. The study also examined which participants were exposed to which agricultural chemicals.

"We mapped where our study participants' lived during pregnancy and around the time of birth. In California, pesticide applicators must report what they're applying, where they're applying it, dates when the applications were made and how much was applied," Hertz-Picciotto said. "What we saw were several classes of pesticides more commonly applied near residences of mothers whose children developed autism or had delayed cognitive or other skills."

The researchers found that during the study period approximately one-third of CHARGE Study participants lived in close proximity - within 1.25 to 1.75 kilometers - of commercial pesticide application sites. Some associations were greater among mothers living closer to application sites and lower as residential proximity to the application sites decreased, the researchers found.

Organophosphates applied over the course of pregnancy were associated with an elevated risk of autism spectrum disorder, particularly for chlorpyrifos applications in the second trimester. Pyrethroids were moderately associated with autism spectrum disorder immediately prior to conception and in the third trimester. Carbamates applied during pregnancy were associated with developmental delay.

Exposures to insecticides for those living near agricultural areas may be problematic, especially during gestation, because the developing fetal brain may be more vulnerable than it is in adults. Because these pesticides are neurotoxic, in utero exposures during early development may distort the complex processes of structural development and neuronal signaling, producing alterations to the excitation and inhibition mechanisms that govern mood, learning, social interactions and behavior.

"In that early developmental gestational period, the brain is developing synapses, the spaces between neurons, where electrical impulses are turned into neurotransmitting chemicals that leap from one neuron to another to pass messages along. The formation of these junctions is really important and may well be where these pesticides are operating and affecting neurotransmission," Hertz-Picciotto said.

Research from the CHARGE Study has emphasized the importance of maternal nutrition during pregnancy, particularly the use of prenatal vitamins to reduce the risk of having a child with autism. While it's impossible to entirely eliminate risks due to environmental exposures, Hertz-Picciotto said that finding ways to reduce exposures to chemical pesticides, particularly for the very young, is important.

"We need to open up a dialogue about how this can be done, at both a societal and individual level," she said. "If it were my family, I wouldn't want to live close to where heavy pesticides are being applied."

Janie F. Shelton, Estella Marie Geraghty, Daniel J. Tancredi, Lora D. Delwiche, Rebecca J. Schmidt, Beate Ritz, Robin L. Hansen, Irva Hertz-Picciotto.Neurodevelopmental Disorders and Prenatal Residential Proximity to Agricultural Pesticides: The CHARGE Study. Environmental Health Perspectives, 2014; DOI:10.1289/ehp.1307044

Colon has safety mechanism that restricts tumor formation

June 23, 2014 - Colon cancer development starts with the formation of benign tumours called adenomas. It is estimated that between 30% and 50% of people over 50 will develop one of these tumours. These adenomas or polyps are the pre-cancerous lesions that, once they accumulate further genetic mutations over many years, can progress to colon cancer. A team headed by scientists at the Institute for Research in Biomedicine (IRB Barcelona) and headed by the ICREA researcher Eduard Batlle has discovered that the colon has a safety mechanism to restrict the formation and growth of adenomas. The study was published in the advanced online edition of the journal Nature Cell Biology and will be the cover of the July issue.

The scientists have observed that the formation of an adenoma in the colon is accompanied by an increase in the production of a molecule called BMP (bone morphogenetic protein). The study explains that BMP limits the self-renewal capacity of adenoma stem cells, thus impeding the rapid development of the lesion. "Colon epithelial cells respond to the presence of these tumours and attempt to suppress them or at least control them through the BMP pathway. Without this safety circuit, we would have many more polyps showing rapid growth. Colon cancer is a disease that develops slowly and this slowness may be caused by this safety mechanism," says Eduard Batlle, head of the Colorectal Cancer Laboratory at IRB Barcelona whose research interests include the study of how colon cancers arise and how they become malignant.

Do we all have the same capacity to deal with polyps?

One hypothesis that has arisen from the study is that we are not equally protected and that there are genetic variations in the population that determine that some people have more robust safety mechanisms to respond to polyp formation than others.

This hypothesis is supported by the fact that the scientists have identified a genomic region through which BMP protein production is controlled, that is to say, the specific site that regulates the safety circuit triggered when adenomas are detected. It is the same site that holds certain genomic variations in the population that are associated with susceptibility to colon cancer. These genomic variations have been revealed by studies in the population and by analysis of the genomes of colon cancer patients that are available in data bases such as that of the 1000 Genomes Project Data.

"We provide a plausible explanation of why certain genomic variations (called snip - SNP-) are associated with a greater risk of colon cancer and we believe it is because these variations affect this safety system that protects us from adenomas," explain the scientists.

"This basic study will allow more defined research into the genomic variations associated with colon cancer that are in the region where BMP is regulated." A better understanding of the mechanism that accelerates or restricts the development of cancer may allow, for example, the discovery of new biomarkers to better identify the population at greatest risk of colon cancer and even the current degree of risk.

Colon cancer is one of the four most prevalent cancers, together with breast, prostate and lung cancer, and it has a global incidence of 1,600,000 cases per year with a mortality rate of 50%. The researchers highlight that if those over 50 underwent preventive tests such as colonoscopies then 80% of the deaths from this disease would be averted.

The study has involved the participation of groups from the "Centro Nacional de Investigaciones Oncológicas," the "Hospital Clínico de Barcelona-IDIBAPS-UB," and the Centre for Genomic Regulation. Funding was provided by an ERC Grant from the European Research Council awarded to Eduard Batlle, from the Josep Steiner Foundation of Switzerland, and from the Spanish Ministry of the Economy and Competitiveness.

Gavin Whissell, Elisa Montagni, Paola Martinelli, Xavier Hernando-Momblona, Marta Sevillano, Peter Jung, Carme Cortina, Alexandre Calon, Anna Abuli, Antoni Castells, Sergi Castellvi-Bel, Ana Silvina Nacht, Elena Sancho, Camille Stephan-Otto Attolini, Guillermo P. Vicent, Francisco X. Real, Eduard Batlle. The transcription factor GATA6 enables self-renewal of colon adenoma stem cells by repressing BMP gene expression. Nature Cell Biology, 2014; DOI:10.1038/ncb2992

Conclusive evidence that sunscreen use in childhood prevents development of malignant melanoma in adults

Research conducted at the Texas Biomedical Research Institute, published in the latest issue of the scientific journal Pigment Cell and Melanoma, has established unequivocally in a natural animal model that the incidence of malignant melanoma in adulthood can be dramatically reduced by the consistent use of sunscreen in infancy and childhood. According to senior author John L. VandeBerg, Ph.D., the research was driven by the fact that, despite the increasing use of sunscreen in recent decades, the incidence of malignant melanoma, the most aggressive form of skin cancer, continues to increase dramatically. The American Cancer Society estimates that more than 75,000 new cases of melanoma will be diagnosed in the U.S. this year.

"While sunscreen is highly effective in preventing sunburn, this paradox has led some to question whether sunscreen is effective in preventing melanoma caused by ultraviolet (UV) light," VandeBerg said. "It has been suggested that sunscreen enables people to receive more UV exposure without becoming sunburned, and that increased exposure to UV light has led to an increasing incidence of melanoma."

Questions regarding the effectiveness of sunscreen have remained unanswered in part because, until recently, no natural mammalian model of UV-induced melanoma has existed, noted VandeBerg. Scientists at Texas Biomedical Research Institute have established the gray short-tailed opossum, a small marsupial from South America, as such a model, and tested an over-the-counter facial lotion containing SPF15 sunscreen for its ability to prevent UV-induced melanoma.

The Texas Biomed researchers found that the application of lotion containing sunscreen to infant opossums led to a 10-fold reduction in pre-melanotic lesions (known to progress to melanoma), in comparison to infant opossums receiving lotion that did not contain sunscreen. This difference in the development of lesions occurred even when low doses of UV light were applied - so low that they caused no sunburn or even reddening of the skin in the opossums that did not receive sunscreen.

The pre-melanotic lesions did not appear until the infants had become adolescents (equivalent to early teenagers in humans), and prior experiments established that the pre-melanocytic lesions in opossums do not progress to melanomas until the animals are well into adulthood, as typically occurs in humans.

"Based on these results, we speculate that the reason it is particularly important that sunscreens be used consistently in childhood, and especially in infancy, is because skin cells during growth are dividing much more rapidly than in adulthood, and it is during cell division that the cells are most susceptible to UV-induced damage," said VandeBerg. "Evidence that supports this hypothesis is that melanoma is not induced in adult opossums when their shaved skin is irradiated by UV light in the absence of sunscreen."

The above story is based on materials provided by Texas Biomedical Research Institute. 

Cell stress inflames the gut, research shows

June 23, 2014 - Over 3.5 million people in Europe and the US suffer from Crohn's disease or ulcerative colitis - the two most common forms of IBD. Chronic bowel inflammation is caused by an overreaction of the immune system to the bacteria which naturally occur in the gut. "This overreaction can come about if, for example, the anti-stress mechanism in the cells of the intestinal mucosa does not function correctly," explains Prof. Dirk Haller of the TUM Chair of Nutrition and Immunology.

What Prof. Haller is referring to is the unfolded protein response (UPR) - a sequential chain of signals in the cell, the role of which is to protect the cells against stress. "The UPR is a kind of cell repair mechanism that kicks in when proteins are not properly folded when they are produced - a major cause of cell stress," Haller continues. Any disturbance of the signaling cascade can lead to inflammation and cell death. This damages the cells of the intestinal mucosa, a pre-condition for the development of IBD.

The C/EBP homologous protein (CHOP) plays a major role in activating the UPR. It seems, however, that the CHOP is also involved in the inflammatory process. The research team decided to take a closer look at the CHOP protein. Using a new mouse model, the scientists examined the role of the protein in the development of chronic bowel inflammation. They modified the DNA so that the intestinal epithelial cells of the mice produced larger amounts of the protein.

Damaged cells recover at a slower rate

The higher CHOP protein count made the mice more susceptible to intestinal inflammation. In addition, the inflammation was slower to abate and the intestinal mucosa subsequently required more time to regenerate. "But contrary to what was previously assumed, the higher CHOP concentration is not actually what causes the epithelial cells to die," Haller explains. "Rather, the CHOP proteins inhibit cell division, thus slowing the regeneration of the mucosa following injury."

Such injuries, which can be caused by an infection, are often the first step to chronic inflammation of the bowel. The researchers' findings provide further confirmation that a properly functioning UPR signaling cascade is an essential condition for healthy intestinal mucosa. Regulatory disturbance can seriously impair the protective function of the intestinal epithelium and play a role in the development of chronic intestinal inflammation.

N Waldschmitt, E Berger, E Rath, R B Sartor, B Weigmann, M Heikenwalder, M Gerhard, K-P Janssen, D Haller. C/EBP homologous protein inhibits tissue repair in response to gut injury and is inversely regulated with chronic inflammation.Mucosal Immunology, 2014; DOI: 10.1038/mi.2014.34

Hormone-disrupting activity of fracking chemicals worse than initially found

June 23, 2014 - Many chemicals used in hydraulic fracturing, or fracking, can disrupt not only the human body's reproductive hormones but also the glucocorticoid and thyroid hormone receptors, which are necessary to maintain good health, a new study finds. The results were presented Monday at the joint meeting of the International Society of Endocrinology and the Endocrine Society: ICE/ENDO 2014 in Chicago.

"Among the chemicals that the fracking industry has reported using most often, all 24 that we have tested block the activity of one or more important hormone receptors," said the study's presenting author, Christopher Kassotis, a PhD student at the University of Missouri, Columbia. "The high levels of hormone disruption by endocrine-disrupting chemicals (EDCs) that we measured, have been associated with many poor health outcomes, such as infertility, cancer and birth defects."

Hydraulic fracturing is the process of injecting numerous chemicals and millions of gallons of water deep underground under high pressure to fracture hard rock and release trapped natural gas and oil. Kassotis said spills of wastewater could contaminate surface and ground water.

In earlier research, this group found that water samples collected from sites with documented fracking spills in Garfield County, Colorado, had moderate to high levels of EDC activity that mimicked or blocked the effects of the female hormones (estrogens) and the male hormones (androgens) in human cells. However, water in areas away from these gas-drilling sites showed little EDC activity on these two reproductive hormones.

The new study extended the analysis to learn whether high-use fracking chemicals changed other key hormone receptors besides the estrogen and androgen receptors. (Receptors are proteins in cells that the hormone binds to in order to perform its function.) Specifically, the researchers also looked at the receptor for a female reproductive hormone, progesterone, as well as those for glucocorticoid - a hormone important to the immune system, which also plays a role in reproduction and fertility - and for thyroid hormone. The latter hormone helps control metabolism, normal brain development and other functions needed for good health.

Among 24 common fracking chemicals that Kassotis and his colleagues repeatedly tested for EDC activity in human cells, 20 blocked the estrogen receptor, preventing estrogen from binding to the receptor and being able to have its natural biological response, he reported. In addition, 17 chemicals inhibited the androgen receptor, 10 hindered the progesterone receptor, 10 blocked the glucocorticoid receptor and 7 inhibited the thyroid hormone receptor.

Kassotis cautioned that they have not measured these chemicals in local water samples, and it is likely that the high chemical concentrations tested would not show up in drinking water near drilling. However, he said mixtures of these chemicals act together to make their hormone-disrupting effects worse than any one chemical alone, and tested drinking water normally contains mixtures of EDCs.

"We don't know what the adverse health consequences might be in humans and animals exposed to these chemicals," Kassotis said, "but infants and children would be most vulnerable because they are smaller, and infants lack the ability to break down these chemicals."

This study received funding from the Passport Foundation Science Innovation Fund, the University of Missouri, and from the Environmental Protection Agency, through a STAR predoctoral fellowship awarded to Kassotis.

The above story is based on materials provided by Endocrine Society. 

BPA stimulates growth of an advanced subtype of human breast cancer cells called inflammatory breast cancer

June 23, 2014 - Environmental exposure to the industrial chemical bisphenol A (BPA) lowers the effectiveness of a targeted anti-cancer drug for inflammatory breast cancer, according to a new study that was performed in human cancer cells. The results, which were presented Sunday at the joint meeting of the International Society of Endocrinology and the Endocrine Society: ICE/ENDO 2014 in Chicago, also show that BPA causes breast cancer cells to grow faster.

"Routine exposures to common environmental chemicals like BPA appear to contribute to breast cancer cell progression and to diminish drug treatment efficacy, particularly in inflammatory breast cancer," said principal investigator Gayathri Devi, PhD, associate professor, Department of Surgery, Duke University Medical Center, Durham, N.C.

Inflammatory breast cancer is a rare, aggressive form of breast cancer with one of the worst survival outcomes due to high rate of treatment failure.

"Not everyone with inflammatory breast cancer responds to treatment, and environmental factors are one of many factors thought to explain why," Devi said.

Other studies have pointed to increased cancer risk with exposure to BPA, a hormone-disrupting chemical found in many consumer products, including hard plastics. However, Dr. Devi said, "This to the best of our knowledge is the first study to show BPA's effects in altering effectiveness of a targeted drug treatment approved for use in breast cancer patients including those with inflammatory breast cancer."

This study is a collaboration between Duke University, the Environmental Protection Agency, NC (EPA) and the Biomanufacturing Research Institute and Technology Enterprise (BRITE) at North Carolina Central University. The EPA's library of chemicals called Toxicity Forecaster or ToxCast, a panel of approximately 300 environmental compounds was used in a newly developed automated screening technology for assessing cancer cell behavior parameters. These "high-content, high throughput screening" assays expose living cells to various doses of chemicals and allow for studying of changes in cell growth and survival.

Devi and colleagues subjected cancer cells isolated from the tumors of patients with inflammatory breast cancer to BPA and other common environmental contaminants in the ToxCast library. They tested a wide range of BPA doses and periods of exposure time including the range observed in human blood samples and from environmental exposures in past, published studies. The researchers then analyzed the cellular changes in culture and compared them with cancerous cells not exposed to BPA.

Although BPA is known to mimic estrogen, it also affected inflammatory breast cancer, which are frequently estrogen receptor-negative, meaning they do not respond to estrogen. BPA exposure caused breast cancer cells to grow faster than untreated cancer cells regardless of whether the cancer was estrogen receptor-positive or -negative, the investigators found.

In addition, this study reported that BPA lowered the effectiveness of an approved cancer-fighting drug, lapatinib, used in breast cancer therapy. Other FDA approved anti-cancer drugs are currently being tested by this team. Devi said the results may have immediate implications in cancer treatment. "Cancer patients must understand there's a component in their daily lives that could influence their treatment outcome. These studies provide the foundation for additional research to develop tools that can be used to identify patients who may be at greater risk of developing treatment resistance. Further, the findings could also lead to biomarkers that identify patients who have heavy exposure to chemicals that could diminish the effectiveness of their cancer therapy." Dr. Devi stated. Scott Sauer, a research fellow in the Devi Laboratory in Duke's Department of Surgery, will present the research.

The above story is based on materials provided by Endocrine Society.

Disclaimer: These articles are not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of Pittwater Online News or its staff.