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News - Week 17 - 2009

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Intestinal barrier function in response to abundant or depleted mucosal glutathione in Salmonella-infected rats

Glutathione, the main antioxidant of intestinal epithelial cells, is suggested to play an important role in gut barrier function and prevention of inflammation-related oxidative damage as induced by acute bacterial infection. Most studies on intestinal glutathione focus on oxidative stress reduction without considering functional disease outcome.

Stress Of Isolation Early In Life Linked To Enhanced Juvenile Response To Cocaine

Drug addiction affects millions of people around the world, causing numerous problems ranging from emotional and psychological difficulties to physical and health issues. Initial drug use can be motivated by curiosity or peer pressure, but in some animals, such as rats, it can also be the result of a stressful early life event, such as social isolation. A new study examines the impact of social isolation on the animal’s response to cocaine. The study, Social Isolation During Perinatal Development Alters the Behavioral Response to Cocaine in Juvenile Rats, was conducted by Natasha Lugo-Escobar, Nicole Carreras and Annabell C. Segarra, University of Puerto Rico, School of Medicine, Rio Piedras, PR. The team will present its findings at the 122nd Annual Meeting of the American Physiological Society (APS; www.the-aps.org/press), which is part of the Experimental Biology 2009 scientific conference. The meeting will be held April 18-22, 2009 in New Orleans.

Smoke From Cigarettes, Cooking Oil, Wood, Shift Male Cardiovascular System Into Overdrive

Secondhand tobacco smoke and smoke from cooking oil and wood smoke affected cardiovascular function of men and women who were exposed to small doses of the smoke for as little as 10 minutes, according to a study from the University of Kentucky. The study confirmed previous findings that tobacco smoke could possibly harm cardiovascular function. In addition, it extended those findings by showing that cardiovascular responses during brief exposures were similar to those found during longer or higher-level exposures the response occurs with different types of smoke (tobacco, cooking oil and wood smoke) men respond to environmental tobacco smoke with a greater increase in indexes of sympathetic outflow to blood vessels than do women The sympathetic nervous system produces the “fight or flight” response, which drives the heart and blood pressure and may cause damage if activated too long. Women respond with a greater parasympathetic response, dubbed “rest and digest,” which acts as a brake on the heart and blood pressure.
The study, Autonomic responses of men and women to particulate exposures, was conducted by Joyce McClendon Evans, Abhijit Patwardhan, Ashwin Jayanthi and Charles Knapp of the University of Kentucky; Roger Jenkins and Ralph Ilgner of the Oak Ridge National Laboratory; and Eric Hartman of CustomKYnetics, Inc. Ms. Evans will present the findings during the 122nd annual meeting of The American Physiological Society (www.the-aps.org/press), which is part of the Experimental Biology 2009 conference. The meeting will take place April 18-22 in New Orleans.

Exercise-Exposed Fetuses Have Improved Breathing Movements In Utero, A Marker For Healthy Development

Exercise has many benefits for adults, teens, and youngsters. It is less clear what benefit, if any, exercise may have during fetal growth during gestation. Now that scientists have determined that, generally speaking, maternal exercise poses no significant risk to a fetus, studies are underway to examine the mother/fetus/exercise/health connection. One important study is now complete. Entitled The Effects of Maternal Exercise on Fetal Breathing Movements, it was conducted by Stephanie Million and Linda E. May, Kansas City University of Medicine and Biosciences (KCUMB), Kansas City, MO; and Kathleen M. Gustafson, University of Kansas Medical Center (KUMC), Kansas City, KS. The researchers will discuss their findings at the 122nd Annual Meeting of the American Physiological Society (APS; www.the-aps.org/press), which is part of the Experimental Biology 2009 scientific conference. The meeting will be held April 18-22, 2009 in New Orleans.

Differences Among Exercisers And Non-Exercisers During Pregnancy

No one doubts that mothers – especially pregnant mothers – are among the busiest people on earth. And while the benefits of exercise for these women and their developing fetuses are widely known, many expectant mothers do not exercise. A survey examining daily activities of moms-to-be will soon be released as part of a larger study looking at the effect of maternal exercise on fetal development. The results suggest, among other things, that exercising during pregnancy does not require “stealing” time from other activities. The study was conducted by Linda E. May, Kansas City University of Medicine and Biosciences (KCUMB), Kansas City, MO; Alan Glaros, KCUMB, and Kathleen M. Gustafson, University of Kansas Medical Center, Kansas City, KS and is entitled Differences Among Exercisers and Non-Exercisers During Pregnancy.

Oral Contraceptives Impair Muscle Gains In Young Women

Many active young women use oral contraceptives (OC) yet its effect on their body composition and exercise performance has not been thoroughly studied. A team of researchers has now examined the effects of OC on female muscle mass, and found that oral contraceptive use impairs muscle gains in young women, and is associated with lower hormone levels.The findings are contained in a new study entitled Oral Contraceptive Use Impairs Muscle Gains in Young Women. It was conducted by Chang-Woock Lee and Steven E. Riechman, Department of Health and Kinesiology, Texas A&M University, College Station, TX; and Mark A. Newman, Human Energy Research Laboratory, University of Pittsburgh, Pittsburgh, PA.

Caffeine Appears To Be Beneficial In Males–But Not Females–With Lou Gehrig’s Disease

Amyotrophic lateral sclerosis (ALS) is a fatal disease that damages key neurons in the brain and spinal cord. The disease causes progressive paralysis of voluntary muscles and often death within five years of symptoms. Although ALS (Lou Gehrig’s disease) was discovered over a century ago, neither the cause nor a cure have been found, but several mechanisms seem to play a role in its development, including oxidative stress. Researchers agree that ALS is a multifactorial disease that involves a complex interplay between a genetic predisposition and environmental factors. One environmental factor is diet. With oxidative stress (which damages the cells) a common concern in ALS pathology, it is worth examining what role antioxidants (which confer benefits to the cells) might play. Antioxidants (the vitamins and nutrients that protect the cells from damage) are found in commonly consumed beverages and foods. Coffee in particular has received attention as a potent dietary antioxidant. It is worth noting that coffee has significantly more antioxidant capacity than cocoa and green, black or herbal teas. However, coffee contains several components, the largest of which are caffeine and chlorogenic acid, a dietary polyphenol that is beneficial to the immune system. Previous studies have shown positive effects with coffee, caffeine, or chlorogenic acid supplementation in improving oxidative stress and its associated cell death mechanisms.

UCSF, Stanford Study Reveals Neural Networks Targeted in Brain Diseases

Scientists are reporting the strongest evidence to date that neurodegenerative diseases target and progress along distinct neural networks that normally support healthy brain function. The discovery could lead to earlier diagnoses, novel treatment-monitoring strategies, and, possibly, recognition of a common disease process among all forms of neurodegeneration. The study, reported in the April 16 issue of the journal "Neuron," was conducted by scientists at the University of California, San Francisco and the Stanford University School of Medicine, who characterized their finding as "an important new framework for understanding neurodegenerative disease." The finding inspired the image for the cover of the issue of the journal. Researchers have known that neurodegenerative diseases are associated with misfolded proteins that aggregate within specific populations of neurons in the brain. Alzheimer's disease, for instance, results from misfolding events involving beta-amyloid and tau proteins, which result in neuritic plaque and neurofibrillary tangle formation in medial temporal memory structures. In all neurodegenerative diseases, synapses between nerve cells falter, and damage spreads to new regions, accompanied by worsening clinical deficits. In most cases, however, scientists have not known what determines the specific brain regions affected by a disease. The current neuroimaging study, which examined patients with five forms of early age-of-onset dementia -- Alzheimer's disease, behavioral variant frontotemporal dementia, semantic dementia, progressive nonfluent aphasia, and corticobasal syndrome - as well as two groups of healthy controls, showed that each disease targets a different neural network. "The study suggests that these diseases don't spread across the brain like a plaque but instead travel along established neural network pathways," says the lead author of the study, William W. Seeley, MD, assistant professor of neurology at the UCSF Memory and Aging Center.

Stanford researchers harness nanoparticles to track cancer cell changes

The more dots there are, the more accurate a picture you get when you connect them. A new imaging technology could give scientists the ability to simultaneously measure as many as 100 or more distinct features in or on a single cell. In a disease such as cancer, that capability would provide a much better picture of what’s going on in individual tumor cells. A Stanford University School of Medicine team led by Cathy Shachaf, PhD, an instructor in microbiology and immunology, has for the first time used specially designed dye-containing nanoparticles to simultaneously image two features within single cells. Although current single-cell flow cytometry technologies can do up to 17 simultaneous visualizations, this new method has the potential to do far more. The new technology works by enhancing the detection of ultra-specific but very weak patterns, known as Raman signals, that molecules emit in response to light.

Long-lasting Nerve Block Could Change Pain Management

Injectable local anesthetic shows promise for prolonged pain relief without toxicity. Boston, Mass. -- Researchers at Children's Hospital Boston have developed a slow-release anesthetic drug-delivery system that could potentially revolutionize treatment of pain during and after surgery, and may also have a large impact on chronic pain management. In NIH-funded work, they used specially designed fat-based particles called liposomes to package saxitoxin, a potent anesthetic, and produced long-lasting local anesthesia in rats without apparent toxicity to nerve or muscle cells. The research will be published online on April 13 by the Proceedings of the National Academy of Sciences. "The idea was to have a single injection that could produce a nerve block lasting days, weeks, maybe even months," explains Daniel Kohane, MD, PhD, of the Division of Critical Care Medicine in the Department of Anesthesiology at Children's, and the report's senior author. "It would be useful for conditions like chronic pain where, rather than use narcotics, which are systemic and pose a risk of addiction, you could just put that piece of the body to sleep, so to speak."

New way to analyze sleep disorders

Sleep is such an essential part of human existence that we spend about a third of our lives doing it -- some more successfully than others. Sleep disorders afflict some 50-70 million people in the United States and are a major cause of disease and injury. People who suffer from disturbed sleep have an increased risk of heart attack, stroke, hypertension, obesity, depression, and accidents. Nearly a fifth of all serious car crashes, in fact, are linked to sleeplessness. Diagnosing sleep disorders is not necessarily easy. In standard "sleep studies," people spend one or more nights at hospitals or other inpatient centers, sleeping while sensors and electrodes attached to the head and torso record breathing, brain waves, heart rate, and other vital signs. Now, a group of scientists in Israel and Germany has discovered a simple new way to monitor sleep and potentially diagnose sleep disorders just by recording someone's heart rate. Their method relies on using a mathematical technique to analyze these recordings and tease out information related to the synchronization between heartbeat and breathing, which might be a measure of fitness of the cardio-respiratory system. Their work may one day help clinicians more easily diagnose sleep disorders and determine optimal treatments for people with congestive heart failure. Athletes might also be able analyze their own recordings to optimize workouts. Conducted by researchers at Technische Universität Ilmenau in Germany, Bar-Ilan University in Ramat Gan, Israel, Martin-Luther-Universität Halle-Wittenberg in Germany, and Schlafmedizinisches Zentrum der Charité Berlin, the work appears in a special focus issue of the journal Chaos, which is published by the American Institute of Physics (AIP). The special issue is focused on nonlinear dynamics in cognitive and neural systems. It asks how chaos affects certain brain areas and presents interdisciplinary approaches to various problems in neuroscience -- including sleep disorders.

New minimally invasive surgery option for patients with stomach cancer

A novel, minimally invasive surgical approach to treat stomach cancer has been shown to have advantages that may make it a preferable treatment for some patients. A new study led by researchers at Memorial Sloan-Kettering Cancer Center (MSKCC) compares traditional "open" surgery to remove the stomach with laparoscopic gastrectomy – a minimally invasive procedure in which the surgeon removes the stomach while guided by a magnified image projected by a thin, lighted tube with a video camera at its tip, called a laparoscope. The findings demonstrate that while laparoscopic surgeries generally took longer to perform than open procedures, the minimally invasive approach yielded shorter hospital stays, decreased need for postoperative pain relief, fewer complications after surgery, and similar rates of recurrence-free survival after 36 months of follow-up. "Our number one goal in treating patients with stomach cancer is to remove the cancer completely and safely, while preserving his or her quality of life," says the study's lead author Vivian E. Strong, MD, a surgeon at MSKCC who specializes in laparoscopic surgery for the treatment of stomach cancer, also known as gastric cancer. "Laparoscopic gastrectomy is an excellent option for certain patients with the disease, and for those patients, this approach has the same success rate as standard open surgery, with significantly fewer complications." Published online in the Annals of Surgical Oncology, the paper describes the largest US study of laparoscopic gastrectomy to date and demonstrates both the safety and efficacy of the procedure. The study examined the surgical characteristics and oncologic outcomes of 30 patients who underwent laparoscopic gastrectomy and compared them to 30 patients who had open gastrectomies. The patients in each group were matched for cancer stage, age, and gender, and had their surgeries during the same time period. In addition to the benefits seen among the patients who underwent laparoscopic gastrectomy, researchers also observed that this approach enabled adequate lymph node retrieval, an important part of a complete cancer surgery in which nearby nodes are removed and then carefully examined for the presence of cancer cells to determine whether the cancer has spread. According to the authors, this finding addresses an ongoing controversy that questions whether removal of the lymph nodes and other oncologic features of the resection during laparoscopic gastrectomy are equivalent to open surgery, particularly given the technical demands of the minimally invasive approach and the learning curve required to perform an adequate resection.

Genetic Abnormality May Increase Risk of Blood Disorders

Researchers at Memorial Sloan-Kettering Cancer Center (MSKCC) have shown for the first time that a tendency to develop some blood disorders may be inherited. Their research, published online today in Nature Genetics, identifies a common genetic sequence abnormality that enhances the likelihood of acquiring a mutation in a gene linked to certain blood diseases. The investigators carried out a genome-wide study to identify inherited DNA sequence changes that frequently occur in patients with myeloproliferative neoplasms, in which several types of blood cells are excessively produced in the bone marrow. They found that an inherited alteration in the gene for JAK2 - a protein with enzymatic activity that is linked to the abnormal production of blood cells - is more common in patients with these disorders. Importantly, patients who inherited this JAK2 alteration were predisposed to acquiring another JAK2 mutation on the same DNA strand. According to the research, these mutations do not arise randomly, but are specifically determined by the DNA sequence.

HIV dearms protective protein in cells

The AIDS-causing HIV specifically counteracts the mechanisms of human cells that protect these against viral infections – a special viral protein marks protective cellular proteins for their rapid destruction and thus diminishes the cell’s supply. A team of researchers in Heidelberg under supervision of virologist Dr. Oliver Keppler demonstrated this mechanism for the first time in cell cultures, thus discovering a target for a novel treatment strategy. Another important discovery of the Heidelberg virologists – this strategy of the human HIV is not effective in a rat model for AIDS. The protective protein in rats is immune to HIV counteraction. Consequently, HIV cannot propagate itself as easily in the animal model as in humans – one limitation of the current rat model. However, this new knowledge may enable an improvement of the small animal model developed by the Heidelberg researchers. The study was published in the journal Cell Host & Microbe in March 2009.

“First Aid” for Brain Cells Comes From Blood

In acute ischemic stroke, the blood supply to the brain is restricted. Initially, brain cells die from lack of oxygen. In addition, ischemia activates harmful inflammatory processes in the affected area of the brain. For the first time, scientists at the Neurology Clinic at Heidelberg University Hospital have shown that certain immune cells in the blood inhibit inflammation after a stroke. These cells are known as regulatory T lymphocytes (Treg). The regulator cytokine Interleukin 10 plays an important role in this protection, perhaps offering a new approach to stroke therapy. The study has now been published in Nature Medicine.  Every year, some 200,000 people suffer a stroke in Germany. It is still frequently fatal or causes severe disability. The Neurology Clinic in Heidelberg under the direction of its medical director Professor Dr. Werner Hacke is one of the most prestigious centers in the world for developing and testing innovative approaches to stroke treatment. Immune cells produce the protective Interleukin 10.

Changing climate will lead to devastating loss of phosphorus from soil

Crop growth, drinking water and recreational water sports could all be adversely affected if predicted changes in rainfall patterns over the coming years prove true, according to research published this month in Biology and Fertility of Soils. Scientists from Biotechnology and Biological Sciences Research Council (BBSRC)-funded North Wyke Research have found for the first time that the rate at which a dried soil is rewetted impacts on the amount of phosphorus lost from the soil into surface water and subsequently into the surrounding environment. Dr Martin Blackwell who is one of the project leaders said: "Our preliminary results show that despite best efforts, the changing climate may limit our ability to mitigate phosphorus losses at certain times of the year, especially summer. "This is really worrying because high phosphorus concentrations in surface waters can lead to harmful algal blooms which can be toxic, cause lack of oxygen during their decay and disrupt food webs. This can also affect the quality of water for drinking and result in the closure of recreational water sport facilities." Under laboratory conditions Dr Blackwell and his team re-wet dried samples of UK grassland soil over different time periods, ranging from two hours to 24 hours using the same quantity of water. The leachate – water that has washed through the soil – was then analysed for phosphorus. The study showed that the rate at which a dried soil is rewetted affects the concentration and forms of phosphorus lost in leachate which could potentially contaminate surface water bodies (e.g. rivers and lakes).

Non-drug treatment of Alzheimer’s disease - long-term benefit not proven

Reliable conclusions about the potential for benefit and harm are currently not possible / In general there is still a great need for good studies on non-drug interventions. Whether people with Alzheimer's disease benefit in the long term from non-drug treatment interventions remains an unanswered question. This unsatisfactory finding is mainly due to the fact that convincing studies are lacking so far. For individual approaches, the studies provide indications of a benefit, but also of harm. This is the result of the final report by the Institute for Quality and Efficiency in Health Care (IQWiG) published on 17 March 2009. According to IQWiG, a general problem of the benefit assessment of non-drug treatment interventions is particularly shown in the therapy of Alzheimer's disease: small research budgets and an underdeveloped study methodology lead to the situation that even for procedures with potential, no reliable conclusions can be drawn and thus no proof of a benefit can be provided.

A new method for bone-marrow-derived liver stem cells isolation and proliferation

Great interest has been aroused in the identification and isolation of liver stem cells from bone marrow cells. Several subsets of bone marrow cells have been found to have the potential to differentiate into hepatocytes, however, sorting based on immunological methods is difficult because of the complicated surface markers of the stem cells; furthermore, no report of successful passage has been published. A research article to be published on April 7, 2009 in the World Journal of Gastroenterology addresses this question. The research team led by Dr. Cai and his colleagues from the Affiliated Foshan Hospital and the Second Affiliated Hospital of Sun Yat-sen University established a carefully designed culture system to isolate, proliferate and differentiate liver stem cells directly from bone marrow cells, and they were able to achieve six passages of the stem cells. The results suggest that BDLSCs can be purified and passaged. The selecting culture system that contains cholestatic serum can purify BDLSCs directly from bone marrow cells, which provides an easy method to separate stem cells, by avoiding complicated immunological manipulation. The successful passage of the stem cells further verifies the proliferating ability of the cells, although the passage is limited, and further research will provide more experience. In this study, the authors used their original method to retrieve the cells, which are possibly BDLSCs. Then, they used fluorescence-activated cell sorting to determine the cells' characteristics before and after differentiation. This is an interesting and potentially important study, which suggests that bone-marrow-derived cells can be stimulated to expand and then differentiate into hepatocyte-like cells, which can possibly be used to treat liver disease.

Neurodegeneration study reveals targets of destruction, UCSF, Stanford study shows

Scientists are reporting the strongest evidence to date that neurodegenerative diseases target and progress along distinct neural networks that normally support healthy brain function. The discovery could lead to earlier diagnoses, novel treatment-monitoring strategies, and, possibly, recognition of a common disease process among all forms of neurodegeneration.The study, reported in the April 16 issue of the journal "Neuron," was conducted by scientists at the University of California, San Francisco and the Stanford University School of Medicine, who characterized their finding as "an important new framework for understanding neurodegenerative disease."The finding inspired the image for the cover of the issue of the journal. Researchers have known that neurodegenerative diseases are associated with misfolded proteins that aggregate within specific populations of neurons in the brain. Alzheimer's disease, for instance, results from misfolding events involving beta-amyloid and tau proteins, which result in neuritic plaque and neurofibrillary tangle formation in medial temporal memory structures. In all neurodegenerative diseases, synapses between nerve cells falter, and damage spreads to new regions, accompanied by worsening clinical deficits. In most cases, however, scientists have not known what determines the specific brain regions affected by a disease. The current neuroimaging study, which examined patients with five forms of early age-of-onset dementia -- Alzheimer's disease, behavioral variant frontotemporal dementia, semantic dementia, progressive nonfluent aphasia, and corticobasal syndrome – as well as two groups of healthy controls, showed that each disease targets a different neural network.

Brain mechanisms for behavioral flexibility

New research provides insight into how the brain can execute different actions in response to the same stimulus. The study, published by Cell Press in the April 16 issue of the journal Neuron, suggests that information from single brain cells cannot be interpreted differently within a short time period, a finding that is important for understanding both normal cognition and psychiatric disorders. Humans exhibit incredible flexibility when it comes to adjusting to the demands of a particular task. For example, when the word "blue" is written in red ink, separate responses to the color or the meaning of the word can be elicited. "Although the roles played by the frontal cortex in this kind of switching behavior have been well documented, little is known about how neural pathways governing sensory and motor associations accomplish such a switch," explains senior study author, Dr. Takanori Uka from the Juntendo University School of Medicine in Tokyo. Dr. Uka and coauthor Dr. Ryo Sasaki investigated where and how identical sensory signals are converted into distinct motor signals. The researchers examined the responses of middle temporal (MT) neurons and the associations between MT neurons and downstream functions in monkeys as they switched between direction and depth discrimination tasks. Previous work has shown that the MT area is critical for both direction and depth discrimination. The monkeys were trained to view dots on a screen and to indicate whether dots moved up or down when they saw the color magenta or whether the dots were nearer or father away when they saw the color cyan. "We found that neuronal sensitivities were nearly identical during both the direction and depth discrimination tasks; that is, neural activity depended on the visual stimulus and not the task itself," says Dr. Uka. This finding suggests that inputs to the MT area were not directly responsible for task switching. Importantly, the researchers went on to show that signals from different MT populations were read out to perform different tasks. "We suggest that task switching is accomplished via the communication of distinct populations of MT neurons into a downstream decision system," explains Dr. Uka. "We hypothesize that single neurons probably cannot switch outputs in a short period of time, so the brain realizes behavioral flexibility by preparing separate pathways for each task through learning, and then chooses the appropriate pathways, rather than switching outputs, in a given trial."

Melatonin is an effective treatment for sleep problems in children with autism

A study in the April 15 issue of the Journal of Clinical Sleep Medicine determined that over-the-counter melatonin medication can shorted the length of time it takes for children with autistic spectrum disorder (ASD), Fragile X Syndrome (FXS), or both to fall asleep at the beginning of the night. Results of the study indicated that children who received over-the-counter melatonin treatments experienced significant improvements in total night sleep durations, sleep latency times, and sleep-onset times. Mean sleep duration was longer on melatonin than placebo by 21 minutes, sleep-onset latency was shorter by 28 minutes and sleep-onset time was earlier by 42 minutes. According to the senior author, Beth L. Goodlin-Jones, PhD of the M.I.N.D Institute at the University of California Davis Health System in Sacramento, Calif., treatment with over-the-counter melatonin supplements benefits children of all ages, which helps alleviate some of the additional stress that parents of special-needs children experience. "Sleep onset problems at the beginning of the night are very troublesome for children and their families," said Goodlin-Jones. "Sometimes children may take one to two hours to fall asleep and often they disrupt the household during this time." Authors report that sleep problems are reported in up to 89 percent of children with autism and 77 percent of children with FXS, the most common form of inherited mental impairment ranging from learning problems to mental retardation, and also the most commonly known cause of autism. Dyssomnia (difficulty falling asleep and frequent nighttime awakenings) are among the most commonly reported problems. Researchers hypothesize that difficulty sleeping in these children is increased due to abnormal levels of melatonin, a natural hormone secreted from the pineal gland that is believed to promote sleep at night. The study included information from 12 children between the ages of 2 to 15.25 years. Sleep quality and quantity were measured both objectively and subjectively. Five participants met diagnostic criteria for autism, 3 for FXS, 3 for FXS and ASD, and 1 for FXS alone.

Study suggests that trouble sleeping leads to increased ratings of pain in cancer patients

A study in the April 15 issue of the Journal of Clinical Sleep Medicine suggests that sleep problems lead to increased pain and fatigue in cancer patients. The results indicate that interventions aimed at trouble sleeping would be expected to improve both pain and fatigue in this patient population. Results show that more than half the sample reported having trouble sleeping, with 26 percent reporting moderate or severe trouble sleeping. Compared with patients who reported no trouble sleeping, patients with moderate to severe trouble sleeping reported significantly more fatigue, pain and depressed mood. Using structural equation modeling analysis to evaluate causal relations and directions of effect, the best-fitting model indicates that trouble sleeping led to increased ratings of pain. According to the authors, the relationship between pain and sleep often has been assumed to be reciprocal. In the present study, however, a model of reciprocal causation could not be fit to the data, and models in which pain caused trouble sleeping did not fit as well as the model in which trouble sleeping caused pain. "We believed we would find a bi-directional relationship between insomnia and pain, but instead found that trouble sleeping was more likely a cause, rather than a consequence, of pain in patients with cancer," said lead author Edward J. Stepanski, chief operational officer at the Accelerated Community Oncology Research Network in Memphis, Tenn. The study included demographic, clinical and patient-reported outcomes data from 11,445 cancer patients undergoing treatment at the West Clinic, a large community oncology practice in Memphis. Participants had an average age of 61.5 years, and 74 percent were female. Breast cancer was the most common form of cancer, and about 25 percent of study subjects had received chemotherapy in the last 30 days. Increases in depressed mood also led to increased ratings of pain. Younger age and recent administration of chemotherapy were both associated with increased trouble sleeping. According to the authors, younger patients often receive more aggressive chemotherapy than older patients; therefore, younger patients may be exposed to more treatment-related toxicity.

Treating sleep disorders in people with traumatic brain injury may not eliminate symptoms

A study in the April 15 issue of the Journal of Clinical Sleep Medicine is the first to assess the effectiveness of treating sleep disorders in adults with a traumatic brain injury (TBI). Results indicate that treatment may result in the objective resolution of the sleep disorder without improvements in daytime sleepiness or neuropsychological function. Results show that in brain-injured subjects with obstructive sleep apnea (OSA), three months of treatment with continuous positive airway pressure (CPAP) therapy dramatically reduced the severity of OSA from 31.4 to 3.8 apneas and hypopneas per hour of sleep; however, there was no demonstrable improvement in measures of daytime sleepiness. Participants experienced no significant changes in measures of mood, quality of life and cognitive performance after treatment for a sleep disorder. According to principal investigator Richard J. Castriotta, M.D., director of the division of Pulmonary, Critical Care and Sleep Medicine at the University of Texas Health Science Center in Houston, researchers were not surprised by the fact that patients with sleep disorders had more severe injuries; however the lack of improvement in excessive sleepiness and neuropsychological testing after treatment was unexpected. "The TBI patients with sleep apnea and no improvement in sleepiness may have had a combination of pre-existing sleep apnea and posttraumatic hypersomnia, causing sleepiness after the injury," said Castriotta. "These patients may need stimulant therapy in addition to CPAP in order to improve symptoms." The study involved 57 adults with an average age of 39 years who had suffered a traumatic brain injury at least three months earlier (average 68 months). Seventy-seven percent of the injuries (44) were incurred as a result of a motor-vehicle accident; other causes were assault, a fall or a falling object. Sixty-one percent of the subjects (35) were free of a sleep disorder, while 23 percent (13) had OSA, 7 percent (4) had periodic limb movements in sleep (PLMS), 5 percent (3) had narcolepsy without cataplexy and 3 percent (2) had post-traumatic hypersomnia.
Participants underwent objective evaluation by overnight polysomnography to detect the presence of sleep disorders, and both objective and subjective tests were used to measure daytime sleepliness, mood, quality of life and cognitive performance. Subjects who were diagnosed with OSA received individualized treatment with CPAP therapy while those suffering from narcolepsy, post-traumatic hypersomnia and PLMS received predetermined dosages of medications that were not adjusted after assessment. According to the authors, research has shown that some OSA patients have residual hypersomnia despite adequate CPAP therapy, which may explain the lack of improvement in measures of daytime sleepiness. Castriotta stated that the study illustrates how difficult it can be to measure the burden of sleep disorders in people with traumatic brain injuries.

Increased symptoms lead mentally disordered to become victims of violence

Contrary to common stereotypes, individuals with major mental disorders are more likely to become victims of violent crimes when they are experiencing an increase in symptoms than they are to commit crime, according to a new study by Brent Teasdale, an assistant professor of criminal justice at Georgia State University. Teasdale found that patients experiencing delusions, hallucinations and worsening symptoms generally are most likely to become victims of violence. In addition, individuals with mental disorders are particularly vulnerable for victimization during times of homelessness and when suffering from alcohol abuse. "They actually have higher rates of victimization than they have of violence commission, which I think is counter to the stereotype that highly symptomatic, obviously delusional, visibly mentally disordered people are dangerous, unpredictable and violent," Teasdale said. "There's no one size fits all approach to these delusions, but the odds of victimization are multiplied almost by a factor of two when a person experiences these delusions."  Teasdale analyzed data from the MacArthur Violence Risk Assessment Study, a longitudinal study of psychiatric patients released from three psychiatric hospitals in Pittsburgh, Pa., Kansas City, Mo., and Worchester, Mass. During the MacArthur study, participants were interviewed every 10 weeks for one year about violence committed against them, stress, symptoms and social relationships. When individuals with mental disorders experience increases in delusions, symptom severity and alcohol problems they may be more focused on their internal states and have fewer cognitive resources available to devote to interactions with other people, Teasdale said. Other research suggests that victimization happens because caretakers may be driven away, leaving the disordered unprotected.

Biofuels Could Hasten Climate Change

A new study finds that it will take more than 75 years for the carbon emissions saved through the use of biofuels to compensate for the carbon lost when biofuel plantations are established on forestlands. If the original habitat was peatland, carbon balance would take more than 600 years. The study appears in Conservation Biology. The oil palm, increasingly used as a source for biofuel, has replaced soybean as the world’s most traded oilseed crop. Global production of palm oil has increased exponentially over the past 40 years. In 2006, 85 percent of the global palm-oil crop was produced in Indonesia and Malaysia, countries whose combined annual tropical forest loss is around 20,000 square kilometers. Conversion of forest to oil palm also results in significant impoverishment of both plant and animal communities. Other tropical crops suitable for biofuel use, like soybean, sugar cane and jatropha, are all likely to have similar impacts on climate and biodiversity.

Home Tooth Bleaching Slightly Reduces Enamel Strength

New research shows that human teeth lost some enamel hardness after the application of several different products used in the home to whiten teeth. The study suggests that future generations of such products might be reformulated in an effort to reduce these side effects. The researchers noted that teeth typically can restore their previous hardness after losing small amounts of enamel calcification. But this is the first study to show at a nanometer scale – measuring in billionths of a meter – how human teeth are affected by the popular home whiteners. “There is some significant reduction in nano-hardness of enamel, but we are talking on a very minute scale. So even though it may not be visible to the human eye, it’s important for research because that’s how we improve products,” said Shereen Azer, assistant professor of restorative and prosthetic dentistry at Ohio State University and lead author of the study.

Eat, drink and be merry?

Study says junk food makes kids fatter, but happier. Fast food and soft drinks may be making children fatter but they also make them happy. Programs aimed at tackling childhood obesity, by reducing children’s consumption of unhealthy food and drink, are likely to be more effective if they also actively seek to keep children happy in other ways, according to Professor Hung-Hao Chang from National Taiwan University and Professor Rodolfo Nayga from the University of Arkansas in the US. Their findings are published in Springer’s Journal of Happiness Studies. Childhood obesity is a major public health issue worldwide. It is well accepted that unhealthy eating patterns are partly responsible for the increase in childhood obesity. However, very little is known about the relationship between fast food and soft drink consumption and children’s happiness. For the first time, Chang and Nayga looked at the relationship between unhealthy dietary habits and children’s psychological health. In particular, they studied the effects of fast food and soft drink consumption on children’s body weight and unhappiness. Using data from the National Health Interview Survey in Taiwan - a nationwide survey carried out in 2001 – the authors looked at the fast food and soft drink consumption, body weight and level of happiness of 2,366 children aged between 2 and 12 years old. Fast food included French fries, pizza and hamburgers; soft drinks included soda and other sugar-sweetened beverages.

Signals from stroking have direct route to brain

Nerve signals that tell the brain that we are being slowly stroked on the skin have their own specialised nerve fibres in the skin. This is shown by a new study from the Sahlgrenska Academy. The discovery may explain why touching the skin can relieve pain. The specialised nerve fibres in the skin are called CT nerves (C-tactile) and they travel directly to the areas in the brain that are important in the emergence of feelings. ”Basically the signals that tell the brain that we are being stroked on the skin have their own direct route to the brain, and are not blocked even if the brain is receiving pain impulses from the same area. In fact it’s more the opposite, that the stroking impulses are able to deaden the pain impulses,” says Line Löken, postgraduate student in neurophysiology at the Sahlgrenska Academy. The results are being published in the distinguished scientific journal, Nature Neuroscience. The research group examined a group of healthy subjects using a technique called microneurography. “By inserting a thin electrode into a nerve in the forearm we can listen in on the nerve and pick up signals from one of the thousands of nerve fibres that make up a nerve,” explains Associate Professor Håkan Olausson, who is leading the research group behind the discovery, together with Johan Wessberg.

Colon cancer shuts down receptor that could shut it down

Though a high-fiber diet has long been considered good for you and beneficial in staving off colon cancer, Medical College of Georgia researchers have discovered a reason why: roughage activates a receptor with cancer-killing potential. Researchers report in the April issue of Cancer Research that the GPR109A receptor is activated by butyrate, a metabolite produced by fiber-eating bacteria in the colon. The receptor puts a double-whammy on cancer by sending signals that trigger cell death, or apoptosis, and shutting down a protein that causes inflammation, a precursor to cancer. "We know the receptor is silenced in cancer but it's not like the gene goes away," says Dr. Vadivel Ganapathy, corresponding author and chair of the Department of Biochemistry and Molecular Biology in the MCG School of Medicine. Cancer shuts down the receptor by chemically modifying its gene through a process called DNA methylation. It's a typical MO for cancer to turn genes off to suit its purpose which is why DNA methylation inhibitors already are under study for a variety of cancers.

Aspirin and similar drugs may be associated with brain microbleeds in older adults

Individuals who take aspirin or other medications that prevent blood clotting by inhibiting the accumulation of platelets appear more likely to have tiny, asymptomatic areas of bleeding in the brain, according to a report posted online today that will appear in the June print issue of Archives of Neurology, one of the JAMA/Archives journals. Cerebral microbleeds—small deposits of the iron-storing protein hemosiderin in the brain—may be a sign of cerebral small-vessel disease, according to background information in the article. This condition, common among older adults, occurs when the walls of blood vessels in the brain become weakened. When microbleeds occur in certain brain areas, they may indicate a type of small vessel disease known as cerebral amyloid angiopathy, in which the accumulation of amyloid (a protein often related to Alzheimer's disease) causes degeneration of smooth muscle cells and increases the susceptibility of blood vessels to ruptures and hemorrhages. Meike W. Vernooij, M.D., and colleagues at Erasmus MC University Medical Center, Rotterdam, the Netherlands, investigated the relationship between cerebral microbleeds and the use of anti-clotting medications in 1,062 individuals without dementia involved in the Rotterdam Scan Study. Participants (average age 69.6) underwent magnetic resonance imaging examinations in 2005 and 2006. Pharmacy records were used to assess whether any of the individuals took anti-clotting drugs. These included aspirin and carbasalate calcium—called platelet aggregation inhibitors because they prevent the accumulation of platelets that form blood clots. In the years before MRI, 363 (34.2 percent) of the participants had used any anti-clotting drugs, including 245 (23.1 percent) who took platelet aggregation inhibitors (67 taking aspirin and 141 taking carbasalate calcium). Compared with patients who did not use anti-clotting drugs, those who took aspirin or carbasalate calcium were more likely to have cerebral microbleeds visible on MRI. This association was particularly strong among individuals taking these drugs at higher doses, typically used to treat or prevent heart disease. Microbleeds in the frontal lobe were more common among aspirin users than carbasalate calcium users. There was no association between other types of anti-clotting drugs and cerebral microbleeds. "There is currently major interest in bleeding risks with the use of antithrombotic or thrombolytic treatment in persons who have microbleeds that are apparent on MRI because this may affect treatment in patients with cardiovascular or cerebrovascular disease," the authors write. "The cross-sectional design of our analyses prohibited an investigation of whether persons with cerebral microbleeds are at increased risk for symptomatic hemorrhage [excessive bleeding] when using platelet aggregation inhibitors." The beneficial effects of anti-clotting drugs for individuals at risk for heart attack and stroke typically outweigh any risks of bleeding, they note. "Nevertheless, it may be that in selected persons (e.g., those with signs of cerebral amyloid angiopathy), this risk-benefit ratio may differ for certain drugs (e.g., aspirin), thus influencing treatment decision," they conclude.

Use of Pancreatic Islets Show Promise in Diabetes Research, Treatments

The use of pancreatic islets (hormone-producing cells) is increasing in diabetes research and may play an important role in future treatments, according to an article in the April 15 issue of JAMA, a theme issue on diabetes. John S. Kaddis, B.S., of the City of Hope National Medical Center, Duarte, Calif., presented the findings of the article at a JAMA media briefing at the National Press Club in Washington, D.C. "The primary objective of islet-based research is to cure diabetes. Perhaps the most prominent clinical application of this research is currently in the form of cell replacement therapy. With the exception of 1 report in a type 2 diabetic cohort, islet transplantation has been used exclusively for a subset of individuals with type 1 diabetes mellitus and was shown, at least temporarily, to improve glucose control and, in a few cases, to lead to insulin independence," writes Mr. Kaddis and colleagues. With this procedure, pancreatic islets are transplanted from a donated pancreas to a person with diabetes as a means of restoring beta-cell function. The destruction of beta cells in the pancreas is the cause of type 1 diabetes. "Although islet transplantation has been shown to offer both protection against long-term complications of the disease and significant improvement in quality of life, several obstacles remain, such as limited engraftment [acceptance of the islets within the recipient], chronic immunosuppression, and inconsistent supply of human islets. These issues must be addressed if the procedure is to be used as a standard of care for qualified individuals," they write.

Omega-3 Fatty Acids May Benefit Cancer Patients Undergoing Major Operations

New research from Trinity College Dublin published in this month’s Annals of Surgery points to a potentially significant advance in the treatment of patients undergoing major cancer surgery. The study was carried out by the oesophageal research group at Trinity College Dublin and St James’s Hospital. A randomised controlled trial showed omega-3 fatty acids given as part of an oral nutritional supplement resulted in the preservation of muscle mass in patients undergoing surgery for oesopahageal cancer, a procedure normally associated with significant weight loss and quality of life issues. The trial was designed by Professor John V Reynolds, Professor of Surgery at Trinity College Dublin and St James’s Hospital, Dublin, and Dr Aoife Ryan PhD, a research dietitian at St James’s Hospital, Dublin*. Omega 3 fats are essential fats found naturally in oily fish, with highest concentrations in salmon, herring, mackerel, and sardines. Recently food manufacturers have begun to add omega 3 to foods such as yogurt, milk, juice, eggs and infant formula in light of a body of scientific evidence which suggests that they reduce cardiovascular disease risk, blood pressure, clot formations, and certain types of fat in the blood.

Study Reports Success in Treating a Rare Retinal Disorder

Patients with a rare, blinding eye disease saw their vision improve after treatment with drugs to suppress their immune systems, according to researchers at the University of Michigan Kellogg Eye Center. Because autoimmune retinopathy (AIR) is difficult to diagnose, the biggest challenge now is to find biologic markers that identify patients who can benefit from treatment. In a review of 30 patients with autoimmune retinopathy, 21 individuals showed improvement after receiving treatment with immunosuppression therapy. The study, reported in the April issue of Archives of Ophthalmology, is the largest review of AIR cases to date. Improvement was defined by several measures, including the ability to read a minimum of two additional lines on the standard eye chart or expansion of at least 25% in visual field size.

Reversing effects of altered enzyme may fight brain tumor growth

An international team of scientists from the Moores Cancer Center at the University of California, San Diego, the University of North Carolina and several institutions in China have explained how a gene alteration can lead to the development of a type of brain cancer, and they have identified a compound that could staunch the cancer's growth. The researchers, led by Kun-Liang Guan, PhD, professor of pharmacology at the UC San Diego School of Medicine, have shown that when a mutated enzyme fails to do its job, the development of tumor-feeding blood vessels increases, allowing more nutrients and oxygen to fuel cancer growth. They have also shown in the laboratory that they could reverse the mutant enzyme's effects, effectively blocking this process, called angiogenesis, and provide a potential future treatment strategy against some types of brain tumors. They reported their findings in the current issue of the journal Science. According to Guan, researchers have known that a mutation in the gene encoding the enzyme, isocitrate dehydrogenase (IDH1), contributed to certain brain tumors called low grade gliomas and secondary glioblastomas, but no one understood how. Guan, Yue Xiong, PhD, at the University of North Carolina and their co-investigators have now shown that this is because alterations in a specific gene, IDH1, impairs the body's ability to keep a tumor growth-promoting protein, HIF-1 alpha, in check. The IDH1 enzyme works to produce a compound called alpha-KG, which is required for HIF-1 breakdown. Without that control, HIF-1 can run amok, promoting angiogenesis and tumor growth. The team was able to reverse this HIF-1 alpha effect by adding a modified form of alpha-KG to brain tumor cells in culture. "This suggests a direction to exploit cell permeable alpha-KG for potential treatment of brain cancer patients with an IDH1 mutation," Guan said.

University of Toronto chemists uncover green catalysts

A University of Toronto research team from the Department of Chemistry has discovered useful "green" catalysts made from iron that might replace the much more expensive and toxic platinum metals typically used in industrial chemical processes to produce drugs, fragrances and flavours. The synthesis of drugs usually relies on the use of catalysts and the expense of the catalysts influences the ultimate cost of the drug. If the catalyst is toxic, as it usually is when platinum-metals such as ruthenium, rhodium and palladium are used, then it must be removed completely from the synthesized product using costly purification techniques. "With a cheaper and less toxic catalyst, like iron, these drawbacks are avoided," says Professor Robert Morris. The study appeared online in Chemistry - A European Journal on April 9. The successful use of iron as a catalyst in place of the more commonly used ruthenium is surprising since iron has been considered to be a "base metal" of low catalytic activity. The successful trick was to prepare a complex of iron with a structure similar to the most active ruthenium catalyst, says Morris. Chemical catalysts are generally known for their ability to speed up a reaction but they can also influence the structure of the chemical that is produced in that reaction, says Morris. Catalysts used in the synthesis of a chemical used as a drug or fragrance are most valuable when they cause the production of the chemical in one structural form and not the mirror image of that form (i.e. producing a left-handed form and not the right-handed one).

Poor nutrition in the womb causes permanent genetic changes in the offspring

The new science of epigenetics explains how genes can be modified by the environment, and a prime result of epigenetic inquiry has just been published online in The FASEB Journal (http://www.fasebj.org): You are what your mother did not eat during pregnancy. In the research report, scientists from the University of Utah show that rat fetuses receiving poor nutrition in the womb become genetically primed to be born into an environment lacking proper nutrition. As a result of this genetic adaptation, the rats were likely to grow to smaller sizes than their normal counterparts. At the same time, they were also at higher risk for a host of health problems throughout their lives, such as diabetes, growth retardation, cardiovascular disease, obesity, and neurodevelopmental delays, among others. Although the study involved rats, the genes and cellular mechanisms involved are the same as those in humans. "Our study emphasizes that maternal–fetal health influences multiple healthcare issues across generations," said Robert Lane, professor of pediatric neonatology at the University of Utah, and one of the senior researchers involved in the study. "To reduce adult diseases such as diabetes, obesity, and cardiovascular disease, we need to understand how the maternal–fetal environment influences the health of offspring." The scientists made this discovery through experiments involving two groups of rats. The first group was normal. The second group had the delivery of nutrients from their mothers' placentas restricted in a way that is equivalent to preeclampsia. The rats were examined right after birth and again at 21 days (21 days is essentially a preadolescent rat) to measure the amount of a protein, called IGF-1, that promotes normal development and growth in rats and humans. They found that the lack of nutrients caused the gene responsible for IGF-1 to significantly reduce the amount of IGF-1 produced in the body before and after birth.

Many clinicians unaware of federally funded research on alternative therapies

Approximately one in four practicing clinicians appear to be aware of two major federally funded clinical trials of alternative therapies, and many do not express confidence in their ability to interpret research results, according to a report in the April 13 issue of Archives of Internal Medicine, one of the JAMA/Archives journals. Complementary and alternative (CAM) therapies are widely used, but until recently few rigorous studies of their safety and effectiveness have been conducted, according to background information in the article. The National Institutes of Health (NIH) has invested more than $2 billion into this type of scientific research in the past decade. "For this investment to achieve its anticipated social value, clinical research must be translated into improvements in clinical and public health practice—a process fraught with obstacles," the authors write. "For evidence from clinical research to have an impact on medical practice, health care professionals must first be aware of the research. Once aware, health care professionals must be able to interpret these findings, judging both their validity and their implications. Finally, they must apply the scientific evidence to their own practices," they continue. To assess this translation process surrounding CAM research, Jon C. Tilburt, M.D., M.P.H., of the NIH, Bethesda, Md., and Mayo Clinic, Rochester, Minn., and colleagues surveyed 2,400 practicing acupuncturists, naturopaths, internists and rheumatologists about their awareness of and attitudes toward CAM research. A total of 1,561 clinicians (65 percent) completed the survey. Of those, 59 percent were aware of at least one of two major clinical trials recently published on CAM therapies for osteoarthritis of the knee (on assessing acupuncture and the other about the supplement glucosamine); only 23 percent were aware of both trials. Acupuncturists (46 percent) and rheumatologists (49 percent) were more likely to be aware of the acupuncture study than naturopaths (30 percent) and general internists (22 percent), whereas for the glucosamine trial, internists (59 percent) and rheumatologists (88 percent) were more aware than acupuncturists (20 percent) and naturopaths (39 percent). A minority of clinicians in all groups said they were "very confident" in their ability to critically interpret research literature (20 percent of acupuncturists, 25 percent of naturopaths, 17 percent of internists and 33 percent of rheumatologists); more described themselves as "moderately confident" (59 percent of acupuncturists, 64 percent of naturopaths, 67 percent of internists and 59 percent of rheumatologists) "Compared with those who were not aware of CAM trials, clinicians who were aware of CAM trials were much more likely to be rheumatologists, to be practicing in an institutional or academic setting, to have some research experience, to express greater ability to interpret evidence and to report greater acceptance of evidence," the authors write. The results suggest that the translation of CAM trial results into clinical practice may vary widely based on the training, attitudes and experiences of the clinicians who might apply them, they continue. "For clinical research in CAM (and conventional medicine) to achieve its potential social value, concerted efforts must be undertaken that more deliberately train clinicians in critical appraisal, biostatistics and use of evidence-based resources, as well as expanded research opportunities, dedicated training experiences and improved dissemination of research results," the authors conclude.

Researchers identify how PCBs may alter in utero, neonatal brain development

In three new studies — including one appearing online today in the Public Library of Science - Biology (PLoS - Biology) — UC Davis researchers provide compelling evidence of how low levels of polychlorinated biphenyls (PCBs) alter the way brain cells develop. The findings could explain at last — some 30 years after the toxic chemicals were banned in the United States — the associations between exposure of the developing nervous system to PCBs and behavioral deficits in children. "We've never really understood the mechanism by which PCBs produce neurobehavioral problems in children," said Isaac N. Pessah, professor of molecular biosciences, director of the UC Davis Center for Children's Environmental Health and co-author of all three studies. "With these studies we have now shown — from the whole animal level to the molecular level — how PCBs alter the development and excitability of brain cells. And that could explain why PCBs are associated with higher rates of neurodevelopmental and behavioral disorders," said Pessah, who is also a researcher with the UC Davis M.I.N.D. Institute. Together, the studies — published within one month of each other — make a compelling case for the mechanism behind PCBs' harmful effects on human neurological development.

New alternative to biopsy detects subtle changes in cancer cells, Stanford study shows

A drop of blood or a chunk of tissue smaller than the period at the end of this sentence may one day be all that is necessary to diagnose cancers and assess their response to treatment, say researchers at the Stanford University School of Medicine. In a study to be published April 12 in the online version of Nature Medicine, the scientists used a specialized machine capable of analyzing whether individual cancer-associated proteins were present in the tiny samples and even whether modifications of the proteins varied in response to cancer treatments. Although the study focuses on blood cancers, the hope is that the technique might also provide a faster, less invasive way to track solid tumors. "Currently we don't know what's going on in a patient's actual tumor cells when a treatment is given," said oncologist Alice Fan, MD, a clinical instructor in the division of oncology at the medical school. "The standard way we measure if a treatment is working is to wait several weeks to see if the tumor mass shrinks. It would really be a leap forward if we could detect what is happening at a cellular level." Fan, the lead author of the study, performed the research in the laboratory of senior author Dean Felsher, MD, PhD, associate professor of medicine and of pathology and the leader of the Stanford Molecular Therapeutics Program. "This technology allows us to analyze cancer-associated proteins on a very small scale," said Felsher, a member of Stanford's Cancer Center, who studies how cancer genes called oncogenes initiate and influence tumor progression in many types of cancers. "Not only can we detect picogram levels — one-trillionth of a gram — of protein, but we can also see very subtle changes in the ways the protein is modified." Variations in the way a protein is modified, or phosphorylated, can affect how it functions in tumor progression. Cancer cells often evade common therapies by rejiggering their levels of protein expression and degrees of phosphorylation. Analyzing repeated small samples from a tumor undergoing treatment may allow doctors to head off rogue cells at the pass before they have a chance to proliferate into a more resistant tumor or to identify patients likely to fail standard approaches to treatment. Fan and Felsher collaborated with researchers from Palo Alto-based Cell Biosciences, which makes the machine used in this study, to separate cancer-associated proteins in narrow capillary tubes based on their charge, which varies according to modifications on the proteins' surface. Two versions of the same protein — one phosphorylated and one not — can be easily distinguished because they travel different distances in the tube. The researchers then used antibodies to identify the relative amounts and positions of the various proteins.

Mount Sinai researchers discover novel mechanisms that might causally link type 2 diabetes to Alzheimer's disease

A recent study by Mount Sinai faculty suggests that a gene associated with onset of type-2 diabetes also decreases in Alzheimer's disease dementia cases. The research, led by Dr. Giulio Maria Pasinetti, MD, Ph.D., The Aidekman Family Professor in Neurology, and Professor of Psychiatry and Geriatrics and Adult Development at Mount Sinai School of Medicine, was published this week in the scientific journal, Archives of Neurology. "This new evidence is of extreme interest," Dr. Pasinetti tells us, "especially because of the evidence that approximately 60% of Alzheimer's disease dementia cases have at least one serious medical condition primarily associated with type-2 diabetes, a chronic condition which includes high blood glucose content (hyperglycemia) and reduced sensitivity to insulin, among other conditions." "The relationship between type-2 diabetes and Alzheimer's disease is elusive," says Dr. Pasinetti. Not all subjects with type-2 diabetes are affected by Alzheimer's disease, and similarly, not all Alzheimer's disease cases are diabetic. However, in the last few years, epidemiological evidence indicates that, relative to healthy elderly subjects, people of the same age affected by type-2 diabetes are twice as likely to develop Alzheimer's disease dementia. The reason is not known. The new study from Dr. Pasinetti, reported in this week's issue of Archives of Neurology, provides insight into a potential mechanism that might explain the relationship between type-2 diabetes and Alzheimer's disease onset and progression. Dr. Pasinetti and colleagues found that a gene known as proliferator-activated receptor coactivator 1 - (PGC-1 ), a key regulator of glucose content currently investigated as a potential therapeutic target for type-2 diabetes, is also decreased in Alzheimer' disease dementia cases. Most importantly, Dr. Pasinetti reports that PGC-1 decreased in Alzheimer' disease dementia cases with progression of the clinical disease and positively correlates with brain accumulation of ?-amyloid, an abnormal protein highly linked to Alzheimer' disease dementia and brain degeneration. This evidence is of high interest to the field and suggests, for the first time, a strong relationship between decreased content of a gene responsible for type-2 diabetes in Alzheimer's disease dementia cases, says Dr. Pasinetti.

Using PET/CT imaging, UCLA researchers can tell after a single treatment if chemotherapy is working

Oncologists often have to wait months before they can determine whether a treatment is working. Now, using a non-invasive method, researchers at UCLA's Jonsson Comprehensive Cancer Center have shown that they can determine after a single cycle of chemotherapy whether the toxic drugs are killing the cancer or not. Using a combination Positron Emission Tomography (PET) and computed tomography (CT) scanner, researchers monitored 50 patients undergoing treatment for high-grade soft tissue sarcomas. The patients were receiving neoadjuvant chemotherapy treatments to shrink their tumors prior to surgery. The study found that response could be determined about a week after the first dose of chemotherapy drugs. Typically, patients are scanned at about three months into chemotherapy to determine whether the treatment is working.
"The question was, how early could we pick up a response? We wanted to see if we could determine response after a single administration of chemotherapy," said Dr. Fritz Eilber, an assistant professor of surgical oncology, director of the Sarcoma Program at UCLA's Jonsson Cancer Center and senior author of the study. "There's no point in giving a patient a treatment that isn't working. These treatments make patients very sick and have long-term serious side effects. "

Surgical Gel Used to Stop Bleeding Could Confuse Mammograms

Dr. Kathleen Ward noticed something odd when she examined the mammogram of a patient who had recently undergone breast cancer surgery. The Loyola University Health System radiologist saw a suspicious pattern of white specks, much like grains of salt. The specks were calcium deposits similar to microcalcifications that sometimes are a sign of early breast cancer. But it was too early for the patient's breast cancer to have returned because it had been only a month since her lumpectomy. It turns out the microcalcifications were not from cancer. Rather, they were due to a gel that is sometimes used during surgery to stop bleeding. In a recent article in the American Journal of Roentgenology, Ward and colleagues reported seven cases in which the sealant mimicked malignant microcalcifications in mammograms. The sealant, FloSeal, "is not recommenderd for use on breast tissue," Ward and colleagues wrote. Ward is Medical Director of Women's Health Imaging and an assistant professor in the Department of Radiology at Loyola University Chicago Stritch School of Medicine. FloSeal, is among the products surgeons use to stop bleeding when sutures or staples are not sufficient or are impractical. FloSeal generally stops bleeding in two minutes or less. "We hope our study will raise awareness for others who may be using this product or any similar product," said first author Dr. Amy Henkel, a third-year radiology resident at Loyola. Previous studies have described the use of FloSeal in urological surgery, such as kidney resection, and cardiovascular surgery. FloSeal does not cause imaging problems for those procedures, but should not be used in breast surgery, said study co-author Dr. Richard Cooper, a professor in the Department of Radiology at Stritch.

MSU researcher develops vaccine for E. coli diarrheal diseases that kill up to 3 million children annually

A Michigan State University researcher has developed a working vaccine for a strain of E. coli that kills 2 million to 3 million children each year in the developing world. Enterotoxigenic E. Coli, which is responsible for 60 percent to 70 percent of all E. coli diarrheal disease, also causes health problems for U.S. troops serving overseas and is responsible for what is commonly called traveler’s diarrhea. A. Mahdi Saeed, professor of epidemiology and infectious disease in MSU’s colleges of Veterinary Medicine and Human Medicine, has applied for a patent for his discovery and has made contact with pharmaceutical companies for commercial production. Negotiations with several firms are ongoing. “This strain of E. coli is an international health challenge that has a huge impact on humanity,” said Saeed, who has devoted four years to develop a working vaccine at MSU’s National Food Safety and Toxicology Center. “By creating a vaccine, we can save untold lives. The implications are massive.” ETEC affects millions of adults and children across the globe, mainly in southern hemisphere countries throughout Africa and South America. It also poses a risk to U.S. troops serving in southern Asia and the Middle East. Saeed’s breakthrough was discovering a way to overcome the miniscule molecular size of one of the illness-inducing toxins produced by the E. coli bug. Since the toxin was so small, it did not prompt the body’s defense system to develop immunity, allowing the same individual to repeatedly get sick, often with more severe health implications.

Low glycemic breakfast may increase benefits of working out

The benefits of physical activity and a balanced diet are well documented and form the basis of many public health recommendations. This is because each of these factors can independently influence risks for many chronic diseases such as obesity, type 2 diabetes, and some forms of cancer. Some research also suggests that exercise and diet interact to influence health. For instance, exercising after short-term fasting (such as before breakfast) may increase the amount of fat burned. Similarly, consumption of a meal eliciting a low blood glucose response prior to exercise may also boost the use of body fat (instead of glucose). However, most of these studies have used either trained athletes or recreational exercisers, and none has looked at effects of the type of pre-exercise meal on metabolism during and after exercise. To better understand the effects of pre-exercise meal composition on fat metabolism in more typical (sedentary) individuals, a group of researchers headed by Dr. Emma Stevenson at the University of Nottingham conducted a controlled human intervention trial. The results of their study are published in the May 2009 issue of The Journal of Nutrition. As expected, blood glucose concentrations were higher after the HGI than the LGI meals and had returned to baseline levels by the time exercise was commenced, after which they were not influenced by breakfast type. Plasma free fatty acids (FFA; a marker for adipose oxidation) fell after consumption of both HGI and LGI breakfasts, but began to rise at ~2 h post-breakfast in the LGI (but not HGI) treatment. Exercise caused a rapid increase in FFA in both groups, but this was higher in the LGI trial compared to the HGI trial (P < 0.001). Circulating concentrations of FFA were not different between treatments following lunch. Overall, fat oxidation was higher in the LGI treatment than in the HGI treatment (P < 0.05) during the post-breakfast and exercise periods. Following lunch, fullness scores were higher in the LGI trial than in the HGI trial (P < 0.05). The authors concluded that consuming a LGI breakfast increases fat oxidation during subsequent exercise and improved satiety during recovery in sedentary females. As such, individuals trying to shed fat may consider choosing LGI foods eaten prior to when they exercise.

Study Suggests Power of Imagination is More Than Just a Metaphor

We've heard it before: "Imagine yourself passing the exam or scoring a goal and it will happen." We may roll our eyes and think that's easier said than done, but in a new study in Psychological Science, a journal of the Association for Psychological Science, psychologists Christopher Davoli and Richard Abrams from Washington University suggest that the imagination may be more effective than we think in helping us reach our goals. A group of students searched visual displays for specific letters (which were scattered among other letters serving as distractors) and identified them as quickly as possible by pressing a button. While performing this task, the students were asked to either imagine themselves holding the display monitor with both hands or with their hands behind their backs (it was emphasized that they were not to assume those poses, but just imagine them). The results showed that simply imagining a posture may have effects that are similar to actually assuming the pose. The participants spent more time searching the display when they imagined themselves holding the monitor, compared to when they imagined themselves with their hands behind their backs. The researchers suggest that the slower rate of searching indicates a more thorough analysis of items closer to the hands. Previous research has shown that we spend more time looking at items close to our hands (items close to us are usually more important than those further away), but this is the first study suggesting that merely imagining something close to our hands will cause us to pay more attention to it.

Findings show insulin - not genes - linked to obesity

Researchers have uncovered new evidence suggesting factors other than genes could cause obesity, finding that genetically identical cells store widely differing amounts of fat depending on subtle variations in how cells process insulin. Learning the precise mechanism responsible for fat storage in cells could lead to methods for controlling obesity. "Insights from our study also will be important for understanding the precise roles of insulin in obesity or Type II diabetes, and to the design of effective intervention strategies," said Ji-Xin Cheng, an assistant professor in Purdue University's Weldon School of Biomedical Engineering and Department of Chemistry.

A cure for honey bee colony collapse?

For the first time, scientists have isolated the parasite Nosema ceranae (Microsporidia) from professional apiaries suffering from honey bee colony depopulation syndrome. They then went on to treat the infection with complete success. In a study published in the new journal from the Society for Applied Microbiology: Environmental Microbiology Reports, scientists from Spain analysed two apiaries and found evidence of honey bee colony depopulation syndrome (also known as colony collapse disorder in the USA). They found no evidence of any other cause of the disease (such as the Varroa destructor, IAPV or pesticides), other than infection with Nosema ceranae. The researchers then treated the infected surviving under-populated colonies with the antibiotic drug, flumagillin and demonstrated complete recovery of all infected colonies. The loss of honey bees could have an enormous horticultural and economic impact worldwide. Honeybees are important pollinators of crops, fruit and wild flowers and are indispensable for a sustainable and profitable agriculture as well as for the maintenance of the non-agricultural ecosystem. Honeybees are attacked by numerous pathogens including viruses, bacteria, fungi and parasites. For most of these diseases, the molecular pathogenesis is poorly understood, hampering the development of new ways to prevent and combat honeybee diseases. So, any progress made in identifying causes and subsequent treatments of honey bee colony collapse is invaluable. There have been other hypothesis for colony collapse in Europe and the USA, but never has this bug been identified as the primary cause in professional apiaries. "Now that we know one strain of parasite that could be responsible, we can look for signs of infection and treat any infected colonies before the infection spreads" said Dr Higes, principle researcher.This finding could help prevent the continual decline in honey bee population which has recently been seen in Europe and the USA.

Epilepsy Drug Linked to Babies' Lower IQ

Women with epilepsy who took the drug valproate ( Depakote) during pregnancy gave birth to children whose IQ at age 3 averaged up to 9 points lower than the scores of children exposed to other epilepsy drugs, according to a new study. Cold and brown fat raise the prospect of a new method of treating obesity Sven Enerbäck, Professor at the Institute of Biomedicine at the Sahlgrenska Academy, University of Gothenburg, Sweden, is one of the scientists who published their results in The New England Journal of Medicine this week. Studies carried out by Enerbäck and others show that adults use brown fat to convert energy to heat - a discovery that may provide new possibilities in treating overweight and obesity. It has previously been believed that the brown fat found in infants disappears as we grow up, but the new study shows that this is not the case. Brown fat cells have been found in adults, in the lower part of the neck just above the collarbone.

Prenatal Exposure to Hong Kong Flu Associated With Reduced Intelligence in Adulthood

The Hong Kong flu pandemic was responsible for more than 700,000 deaths worldwide in the late 1960s, with major disease outbreaks in Europe in the winter of 1969-1970. A number of studies have been conducted to determine if prenatal exposure to the influenza virus may result in mental disorders that affect a small portion of the population, but no studies have explored the possible effects of prenatal exposure on the mean intelligence in the general population. A new study found that early prenatal exposure to the Hong Kong flu may have interfered with fetal cerebral development and caused reduced intelligence in adulthood. The study is published in Annals of Neurology.

Singapore researchers first to transform carbon dioxide into methanol

Scientists at Singapore's Institute of Bioengineering and Nanotechnology (IBN) have succeeded in unlocking the potential of carbon dioxide – a common greenhouse gas – by converting it into a more useful product. In the international chemistry journal Angewandte Chemie, the IBN researchers report that by using organocatalysts, they activated carbon dioxide in a mild and non-toxic process to produce methanol, a widely used industrial feedstock and clean-burning biofuel. Organocatalysts are catalysts that are comprised of non-metallic elements found in organic compounds. NHCs such as IMes (1,3-bis-(2,4,6 trimethylphenyl)imidazolylidene) are a form of organocatalysts that are stable and easily stored. They do not contain toxic heavy metals and can be produced easily without high costs. The scientists made carbon dioxide react by using N-heterocyclic carbenes (NHCs), a novel organocatalyst. In contrast to heavy metal catalysts that contain toxic and unstable components, NHCs are stable, even in the presence of oxygen. Hence, the reaction with NHCs and carbon dioxide can take place under mild conditions in dry air. The IBN scientists showed that only a small amount of NHC is required to induce carbon dioxide activity in a reaction. "NHCs have shown tremendous potential for activating and fixing carbon dioxide. Our work can contribute towards transforming excess carbon dioxide in the environment into useful products such as methanol," said Siti Nurhanna Riduan, IBN Senior Lab Officer, who is also pursuing her Ph.D. under the Scientific Staff Development Award at IBN, one of the research institutes of Singapore's A*STAR (Agency for Science, Technology and Research). Hydrosilane, a combination of silica and hydrogen, is added to the NHC-activated carbon dioxide, and the product of this reaction is transformed into methanol by adding water through hydrolysis.

Safe exercise for migraine sufferers

Many patients who suffer from migraines avoid taking aerobic exercise because they are afraid that the physical activity may bring on a serious migraine attack. Researchers at the Sahlgrenska Academy, University of Gothenburg, Sweden, have now developed an exercise programme that can improve fitness among migraine sufferers without aggravating this painful condition. Patients who suffer from migraines are often advised to take exercise, but to date no studies have been conducted to show that exercise actually helps guard against migraine attacks. No exercise programme has so far been scientifically proven to be safe for migraine patients. "We know that everyone benefits from a little exercise, but if you're convinced that a session at the gym will end up with you being confined to bed with a thumping headache and nausea then it's hardly surprising that people give it a miss," says Jane Carlsson, Professor in Physiotherapy at the Sahlgrenska Academy. In the study, which is being published in the latest issue of the scientific journal Headache, some twenty migraine sufferers were asked to follow a special exercise programme three times a week for three months. The programme involved using an exercise bike under the guidance of a physiotherapist.
"We could see that those who participated in the study were much fitter after the training period, since their ability to absorb oxygen increased considerably," says physiotherapist Emma Varkey, one of the researchers behind the study. Only one of the patients suffered a migraine attack that was directly linked to the training session. "Now that we've been able to show that the risk of increased frequency of attacks in connection with this type of exercise is extremely small, we can study whether exercise can be used to prevent or alleviate migraine attacks. "We have already initiated a new study in which we plan to compare the results against a control group," says Mattias Linde, neurologist at Cephalea Headache Centre and researcher at the Sahlgrenska Academy.

New therapeutic target for melanoma identified

A protein called Mcl-1 plays a critical role in melanoma cell resistance to a form of apoptosis called anoikis, according to research published this week in Molecular Cancer Research. The presence of Mcl-1 causes cell resistance to anoikis. This resistance to anoikis enables the melanoma cells to metastasize and survive at sites distant from the primary tumor, according to Andrew Aplin, Ph.D., an associate professor of Cancer Biology at Jefferson Medical College of Thomas Jefferson University, and a member of the Kimmel Cancer Center at Jefferson. The research was conducted at Albany Medical College in New York by Dr. Aplin and colleagues. Mcl-1 is part of the Bcl-2 protein family, and is regulated by B-RAF proteins, which are mutated in approximately 60 percent of all human melanomas. The Bcl-2 family includes several prosurvival proteins that are associated with the resistance of cancer cells to apoptosis, or cell death. Dr. Aplin and colleagues analyzed three candidate Bcl-2 proteins: Mcl-1, Bcl-2 and Bcl-XL. "When we depleted Mcl-1 from the tumor cells, they were susceptible to cell death," Dr. Aplin said. "Mcl-1 showed dramatic results compared to Bcl-2 and Bcl-XL, which was a surprise. Our findings show that targeting Mcl-1, which is upregulated in a majority of melanoma cells, could be a viable treatment strategy." Dr. Aplin said there are therapeutic agents in development to target this protein family, but most specifically target Bcl-2 and Bcl-XL. There is one agent in development by Gemin X Biotech that targets Mcl-1. This agent, called obatoclax, is currently in phase I/II trials.

Prenatal meth exposure linked to abnormal brain development

A first of its kind study examining the effects of methamphetamine use during pregnancy has found the drug appears to cause abnormal brain development in children. The research is published in the April 15, 2009, online issue of Neurology®, the medical journal of the American Academy of Neurology. "Methamphetamine use is an increasing problem among women of childbearing age, leading to an increasing number of children with prenatal meth exposure," said study author Linda Chang, MD, with the John A. Burns School of Medicine, University of Hawai`i at M?noa in Honolulu. "But until now, the effects of prenatal meth exposure on the developing brain of a child were little known."For the study, brain scans were performed on 29 three- and four-year-old children whose mothers used meth while pregnant and 37 unexposed children of the same ages. The MRI scans used diffusion tensor imaging to help measure the diffusion of molecules in a child's brain, which can indicate abnormal microscopic brain structures that might reflect abnormal brain development. The scans showed that children with prenatal meth exposure had differences in the white matter structure and maturation of their brains compared to unexposed children. The children with prenatal meth exposure had up to four percent lower diffusion of molecules in the white matter of their brains. "Our findings suggest prenatal meth exposure accelerates brain development in an abnormal pattern," said Chang. "Such abnormal brain development may explain why some children with prenatal meth exposure reach developmental milestones later than others."

New findings resolve long dispute about how the disease might kill brain cells

For a decade, Alzheimer's disease researchers have been entrenched in debate about one of the mechanisms believed to be responsible for brain cell death and memory loss in the illness. Now researchers at the University of Michigan and the University of California, San Diego have settled the dispute. Resolving this controversy improves understanding of the disease and could one day lead to better treatments.
Michael Mayer, an assistant professor in the U-M departments of Biomedical Engineering and Chemical Engineering, and Jerry Yang, an assistant professor in the Department of Chemistry and Biochemistry at UCSD, and their colleagues found a flaw in earlier studies supporting one side of the debate. Their findings are published online in the Journal of Neurotoxicity Research. They will appear in the May print edition.
Their results clarify how small proteins called amyloid-beta peptides damage brain cell membranes, allowing extra calcium ions to enter the neurons. An ion is an electrically-charged particle. An ion imbalance in a cell can trigger its suicide. Amyloid-beta peptides are the prime suspects for causing cell death in Alzheimer's, although other mechanisms could also be to blame. The disease is not well understood. The researchers confirmed evidence found by others that amyloid-beta peptides prick pores into brain cell membranes, opening channels where calcium ions can rush in. This was one mechanism the field had contemplated, but other evidence suggested a different scenario. Some researchers believed that the peptide caused a general thinning of the cell membranes and these thinned membranes lost their ability to keep calcium ions out of brain cells. Mayer and Yang disproved this latter theory. "When you understand these mechanisms better, you have a better chance of being able to pharmaceutically counteract them as a possible treatment. For instance, if amyloid-beta thins membranes, this general effect might be difficult to treat. On the other hand, if it forms pores, this effect might be treatable with pore blockers. Ion channel blockers are medications sold today to treat a variety of diseases," Mayer said. He cautions that much research is needed before it is known whether such medications are effective and safe to treat Alzheimer's. Mayer and Yang were able to explain the other experimental results that blamed cell membrane thinning for uncontrolled calcium ion fluctuations. It turns out that in these studies, trace amounts of residual solvent used to prepare the peptide had a dramatic effect. The Michigan- and UCSD-led team reproduced these experimental results using only the solvent, without the peptide. The solvent is called Hexafluoroisopropanol, or HFIP."HFIP is a good solvent used to break up clumps of the peptide to prepare for experiments, but it's toxic and membrane-active. What we found was that the reported preparation procedure did not remove the solvent effectively," Mayer said. "Our findings are watertight since we could reproduce the thinning effect in the absence of amyloid-beta peptides by this solvent alone."

Gene therapy for muscular dystrophy shows promise beyond safety

Researchers have cleared a safety hurdle in efforts to develop a gene therapy for a form of muscular dystrophy that disables patients by gradually weakening muscles near the hips and shoulders. Described as the first gene therapy trial in muscular dystrophy demonstrating promising findings, researchers from the University of Florida (UF), Nationwide Children's Hospital in Columbus, Ohio, and The Ohio State University report how they safely transferred a gene to produce a protein necessary for healthy muscle fiber growth into three teenagers with limb-girdle muscular dystrophy. The findings, which have relevance to genetic disorders beyond muscular dystrophy as well as conditions in which muscles atrophy, were published online today in the Annals of Neurology. "We think this is an important milestone in establishing the successful use of gene therapy in muscular dystrophy," said Jerry Mendell, MD, director of the Center for Gene Therapy in The Research Institute at Nationwide Children's Hospital and the lead author of the study. "This trial sets the stage for moving forward with treatment for this group of diseases and we are very pleased with these promising initial results. In subsequent steps we plan to deliver the gene through the circulation in hopes of reaching multiple muscles. We also want to extend the trials over longer time periods to be sure of the body's reaction." Mendell is also a professor of Pediatrics and Pathology at The Ohio State University College of Medicine. Limb-girdle muscular dystrophy actually describes more than 19 disorders that occur because patients have a faulty alpha-sarcoglycan gene. In each of the disorders, the muscle fails to produce a protein essential for muscle fibers to thrive. It can occur in children or adults, and it causes their muscles to get weaker throughout their lifetimes. The trial evaluated the safety of a modified adeno-associated virus — an apparently harmless virus known as AAV that already exists in most people — as a vector to deliver the alpha-SG gene to muscle tissue. "The safety data is accumulating because this is the same type of vector that we and other research groups have successfully used in gene therapy trials for other diseases," said Barry Byrne, MD, a UF pediatric cardiologist who is a member of the UF Genetics Institute and director of the Powell Gene Therapy Center. "In this effort, although proof of safety was the main endpoint, the added benefit was that this was an effective gene transfer. Even though we were dealing with a small area of muscle, the effect was long-lasting, and that has never been observed before."

Biodegradable gel being studied as a treatment for esophageal cancer

Gastroenterologists at Rush University Medical Center are studying the safety and efficacy of a new system for delivering chemotherapy for patients with esophageal cancer, a rare, but deadly disease that attacks the throat. The unique drug therapy delivers a highly concentrated dose of chemotherapy injected directly on to the hard-to-reach tumors in the esophagus non-surgically. Researchers at Rush are trying to determine if the gel treatment can reduce the size of the cancerous tumors. Patients diagnosed with esophageal cancer are usually diagnosed at very advanced stages and not only have to undergo chemoradiation therapy, but may also have an esophagectomy, which is a surgical procedure to remove a part of or the entire esophagus. "Patients with esophageal cancer have very few treatment options and life expectancy can be less than two years from first diagnosis," said Dr. Sohrab Mobarhan, principal investigator of the study and clinical director of the Coleman Foundation Comprehensive Clinic for Gastrointestinal Cancers at Rush. "This also could potentially be a viable treatment option for patients who have inoperable tumors located in their esophagus." The investigational drug, called OncoGel, is made of two major components, the ReGel drug delivery system, which is a gel made up of ingredients used in biodegradable stitches, and paxclitaxel, a well established, FDA-approved anti-cancer chemotherapy agent. Patients receive a one-time injection of OncoGel during an endoscopy."In pilot studies, OncoGel has been shown to continuously release paclitaxel, which is the chemotherapy agent, in concentrated doses at a higher magnitude than in just delivering it through the blood for up to six weeks," said Mobarhan. Esophageal cancer can develop when stomach acid backs up into the lower esophagus, in some cases damaging cells in the inner layer of the esophagus. This abnormal cellular change is known as Barrett's esophagus. A person could ultimately develop cancer of the esophagus as a result of developing Barrett's. "Because the symptoms do not seem unusual, the disease can go unnoticed and ignored for long periods of time," said Mobarhan. "A chronic cough, sore throat, indigestion and acid reflux are some of the symptoms that can mask the disease. The lesions that form into cancerous tumors can cause the opening of the esophagus to narrow to nearly half its usual width and make it difficult to swallow." Data indicates that only 16,000 new cases of esophageal cancer are reported in the U.S. in 2008 and more than 14,000 people – almost 90 percent – died from the disease. In an earlier phase of the study of OncoGel in patients with late stage inoperable esophageal cancer, 70 percent of patients had a reduction in tumor volume when OncoGel was used in combination with radiotherapy. In addition, after treatment, biopsy samples did not contain tumor cells in almost 40 percent of patients.

Researchers break the animal kingdom's colour code

Charles Darwin was fascinated by the colours of animals - he once wrote to his colleague Alfred Russell Wallace asking why certain animals were "so beautifully and artistically coloured". It is a question that has intrigued biologists ever since. Now research spearheaded at the University of York (in collaboration with researchersfrom the University of Glasgow, and Carleton University in Canada) has used computer models to trace the evolution of this extravagant colouring. Researchers in the York Centre for Complex Systems Analysis (YCCSA) sought to explain why most animals that have an anti-predatory defence, such as a sting or poison, tend to be brightly coloured. Mimicry is common in nature. Defenceless species frequently evolve to look like a nasty species, so that potential predators cannot distinguish between the two -- a good meal or an unpleasant experience. Such mimicry is good for the defenceless species which predators can mistake for a daunting adversary, but is bad for nasty species which might be mistaken as a good meal. The YCSSA research, published in Evolution, suggests that nasty prey may have evolved bright colours to avoid this kind of mimicry. Bright colours are harder for defenceless prey to mimic because they have a survival cost of increased detectability by predators. There are also many ways to look distinctive when brightly coloured, but limited scope for doing so when camouflaged, because camouflage needs to blend in with the background.

North east of Barcelona and south east of Madrid, the urban centres with the most polluted air

During the summer, the southern region of the Mediterranean basin, where Spain is found, frequently experiences high levels of chemical pollutants in the air. Catalan researchers have studied the contribution of atmospheric processes during the hottest months of the year and have concluded that the areas leeward of Barcelona and Madrid have the poorest air quality levels. To determine the most polluted areas of north east and central Spain in the summer, a team of researchers from the Universidad Politécnica de Cataluña (Polytechnic University of Catalonia) (UPC) and the Barcelona Supercomputing Centre (BSC) has quantified with great precision the atmospheric processes that contribute to the concentration of pollutants. "The worst air quality levels are observed in areas leeward of Barcelona and Madrid, due to the plume of urban contamination that affects the south-south-east region of Madrid and north-north-east of Barcelona", María Gonçalves, principal author of the study and researcher at BSC, explains to SINC. The work, led by José María Baldasano and Pedro Jiménez of BSC and recently published in Atmospheric Chemistry and Physics, has been centred around Catalonia and the Autonomous Community of Madrid as they are home to the two most populated cities, Barcelona and Madrid, "where episodes of atmospheric contamination are frequent", the scientist adds.

New study finds "it's never too late to stop drinking"

Where there is life there is hope and it is never too late to stop drinking, even with the most severe case of alcohol-related liver disease, according to new research from the University of Southampton. However, the downside is that up a quarter of people with alcohol-related cirrhosis die before they get the chance to stop drinking. Alcohol-related cirrhosis develops silently but usually presents with an episode of internal bleeding or jaundice - which is often fatal. The study, led by Dr Nick Sheron, senior lecturer at the University of Southampton and consultant hepatologist at Southampton General Hospital, found that abstinence from alcohol is the key factor in long-term prognosis, even with relatively severe alcohol-related cirrhosis on a liver biopsy. The study 'Alcohol, cirrhosis and mortality' appears in this month's Addiction journal. Its aim was to determine the effect of pathological severity of cirrhosis on survival in patients with alcohol-related cirrhosis. Liver biopsies from 100 patients were scored for the Laennec score of severity of cirrhosis between 1 January 1995 and 31 December 2000, and medical notes were reviewed to determine various clinical factors including drinking status.

Snacking on high GI foods during late pregnancy may lead to the birth of a heavier baby with an increased risk of childhood obesity, says new research

Mothers who snack on high GI (Glycaemic Index) foods like chocolate and white bread during later pregnancy may give birth to heavier babies with a greater risk of childhood obesity, according to new research published in the British Journal of Obstetrics and Gynaecology. The research by scientists from the UCD Conway Institute at University College Dublin, Ireland, and the National Maternity Hospital (NMH) in Dublin, Ireland, into sheep models of pregnancy discovered that high GI snack diets among ewes during the third trimester of pregnancy resulted in a heavier birth weight and postnatal growth rate of newborn lambs. According to the scientists, the sheep model used in the scientific study is instructive of the relationship between a human mothers’ diet, the birth weight of their child, and the risk of childhood obesity. In previous scientific studies, the sheep model has been shown to share many elements of pregnancy with the human model including metabolic function and nutrient transport. For the past 40 years, sheep models have been used to investigate maternal–fetal interactions in humans because sheep have a body weight of 65 to 85 kg, a 17 day (average) reproductive cycle, and they usually have 1 or 2 lambs per pregnancy with a relatively long gestation period of 147 days. Sheep models are also amenable to reproduction, nutritional and surgical manipulation and can tolerate observations like ultrasound and tissue collections such as blood sampling.
“For the first time, in a sheep model, the findings show that ewes fed high glycaemic foods twice daily in addition to their normal meals, during the last trimester of pregnancy, gave birth to heavier lambs with a faster postnatal growth rate,” says Professor Alex Evans, Associate Professor of Animal Physiology at the UCD School of Agriculture, Food and Veterinary Medicine, at University College Dublin, one of the co-authors of the study.

Big Pharma's Thalidomide Drug was Actually Developed as Nazi Chemical Weapon

The notorious drug thalidomide, which produced birth defects in the children of women who were prescribed it as a treatment for morning sickness, appears to have been developed by Nazi concentration camp doctors as a nerve gas antidote. "It is now appearing increasingly likely that thalidomide was the last war crime of the Nazis," said Martin Johnson, director of the Thalidomide Trust and author of one of the papers.
Thalidomide, marketed between 1957 and 1961 by the German company Chemie Grünenthal, caused women to give birth to children with developmental deformities including brain damage and malformed arms, legs, hands and feet. Grünenthal has always claimed that its scientists developed the drug independently while searching for a new antihistamine formula, and the German government has consistently refused to compensate any victims without German citizenship.

Tart Cherries May Help Reduce Belly Fat

A diet containing tart cherries may help reduce the symptoms of metabolic syndrome and the risk of cardiovascular disease, according to a study conducted by researchers from the University of Michigan and presented at the annual meeting of the American Dietetic Association. The study was funded by the Cherry Marketing Institute, which did not have any involvement in its design, implementation or analysis. Metabolic syndrome is a cluster of symptoms that increase the risk of cardiovascular disease and diabetes, including high blood pressure, high triglycerides, high fasting blood sugar, low HDL ("good") cholesterol and central obesity (obesity characterized mainly by belly fat). In the current study, researchers evaluated several symptoms of metabolic syndrome in mice that were fed one of two diets, either with or without added whole tart cherry powder.

Study Finds New Hazard in Third-Hand Smoke

Dr. Jonathan P. Winickoff, the lead author of the study and an assistant professor of pediatrics at Harvard Medical School, explains: "Third-hand smoke is the tobacco smoke contamination that remains after the cigarette is extinguished. It's the toxic layer that is deposited on every surface indoors where a smoker lights up: in cars, on smokers' clothing and hair." In the study, researchers surveyed 1,500 households in the United States to determine if people were aware of the hazards of third-hand smoke. Most smokers and nonsmokers agreed that second-hand smoke was an obvious danger. However, only 65 percent of nonsmokers and 43 percent of smokers thought third-hand smoke was hazardous to children. Most people, and especially those who smoke, simply aren't aware of the risks of third-hand smoke.

Vitamin D Deficiency Linked to Increased C-Section Rate

A study indicates women who are short on vitamin D are more likely to have a cesarean section delivery. The findings can be attributed to the work of a larger study which looked at the vitamin D levels in women within 72 hours of delivery. None of the women in the study had previous c-sections, and the rate of cesarean deliveries during the study was 17 percent. Researchers found 36 percent of women who had delivered babies to be vitamin D deficient, and 23 percent were found to be severely deficient. The findings indicate that a woman with low vitamin D levels is four times more likely to deliver by cesarean than a woman with higher levels.

Relatively low dietary intake of vitamins A and C boosts asthma risk

A relatively low dietary intake of vitamins A and C boosts the risk of asthma, suggests a systematic analysis of the available evidence published ahead of print in the journal Thorax. hese findings clash with a large review of the evidence, which was published last year. Observational studies in recent years have pointed to a link between dietary antioxidant vitamins — A,C, and E — and asthma. But the results of clinical trials have proved inconclusive, claim the authors, from The University of Nottingham.

Low Lead Levels In Children Can Affect Cardiovascular Responses To Stress

Even low levels of lead found in the blood during early childhood can adversely affect how the child’s cardiovascular system responds to stress and could possibly lead to hypertension later in life, according to a study from the State University of New York (SUNY) at Oswego. Lead exposure was associated with an increase in vascular resistance when the children worked on a stressful computer task. Vascular resistance is a measure of tension within the blood vessels. Increased vascular resistance may lead to hypertension if it continues over time. The study also found that lead exposure was associated with a decrease in circulating aldosterone levels. Aldosterone is a hormone that helps regulate blood pressure. The study, Lead exposure and cardiovascular dysregulation in children, was conducted by James A. MacKenzie, Brooks B. Gump, Kristen Roosa, Kestas Bendinskas and Amy Dumas of the State University of New York, Oswego; Robert Morgan of Oswego Family Physicians; and Patrick Parsons of the New York State Department of Health.

Researchers find lack of key molecule leads to deafness

Researchers have identified tiny molecules that may lead to big breakthroughs in the treatment of hearing loss and deafness. An international team, including researchers from Tel Aviv University in Israel and Purdue University, found that lack of these molecules causes abnormal development of the inner ear and leads to progressive hearing loss.Donna Fekete, the Purdue professor of biological sciences involved in the study, said this new information could provide promising leads to treat hearing loss. "The molecules we identified could be used as a molecular tool delivered directly into the ears of deaf people to induce regeneration of important sensory cells that would improve hearing," she said. "The molecules also could potentially help people with balance disorders related to inner ear function such as Meniere's disease."
The National Institutes of Health National Institute on Deafness and Other Communication Disorders, or NIDCD, reports that 36 million American adults have some degree of hearing loss.

Shedding some light on Parkinson's treatment

A research team lead by Karl Deisseroth in the bioengineering department at Stanford University has developed a technique to systematically characterize disease circuits in the brain. By precisely controlling individual components of the circuit implicated in Parkinson's disease, the team has identified a specific group of cells as direct targets of deep brain stimulation (DBS), a Parkinson's treatment. Termed optogenetics, the NSF-funded technology uses light-activated proteins, originally isolated from bacteria, in combination with genetic approaches to control specific parts of the brain. The technique is a vast improvement over previous methods because it allows researchers to precisely stimulate neurons and measure the effect of treatment simultaneously in animals with Parkinson's-like symptoms. Published in the April 17 issue of Science, Deisseroth's team found they could reduce disease symptoms by preferentially activating neurons that link to the subthalamic nucleus region of the brain. First, these specific cells were treated in a way that made them sensitive to stimulation by blue light, then the team implanted an optical fiber in the brain. When researchers rapidly flashed blue light inside the animals' brains the disease symptoms improved. In contrast, treating with slower flashes of light actually made the symptoms worse, and targeting other kinds of cells had no effect at all, indicating both proper cell type and stimulation frequency are crucial components of effective treatment. Flashing blue light on portions of the same neurons found closer to the outer surface of the brain had an effect similar to treatment deep within the brain, raising the possibility that researchers may be able to develop treatments that are less invasive than current options. Approved as a medical treatment in 1997, DBS remains controversial because it doesn't work on all patients. Used to treat Parkinson's disease, depression and movement disorders, DBS involves surgical implantation of a brain pacemaker, which sends electrical impulses into the brain. In the past, researchers have been unable to understand the effective mechanism of DBS because the electrical signal emitted by DBS devices interferes with the ability to observe brain activity.

Scientists Discover New Chemical Reaction for DNA Production in Bacteria and Viruses

A team of researchers has discovered a new chemical reaction for producing one of the four nucleotides, or building blocks, needed to build DNA. The reaction includes an unusual first step, or mechanism, and unlike other known reactions that produce the DNA building block, uses an enzyme that speeds up, or catalyzes, the reaction without bonding to any of the compounds, or substrates, in the reaction. The chemical reaction discovered by the researchers uses an enzyme called flavin-dependent thymidylate synthase, or FDTS. The enzyme is coded by the thyX gene and has been found primarily in bacteria and viruses, including several human pathogens and biological warfare agents. In the future, scientists may use this knowledge for the development of new antibacterial and antiviral drugs. Supported with partial funding from the National Science Foundation (NSF) and led by Amnon Kohen, an associate professor in the departments of chemistry and molecular and cellular biology at the University of Iowa the team reports their findings in the April 16, 2009, issue of Nature, Letters section. Prior to the team's discovery, it was thought that thymidylate synthase, or TS, was the primary enzyme catalyzing a reaction that produced one of the four DNA building blocks called deoxy-thymidine monophosphate. The TS enzyme is coded by the thyA and TYMS genes and is present in most multi-cellular forms of life, including humans.Both the new and classical enzymatic reactions complete a key step in producing the DNA building block by adding a methyl group--one carbon atom attached to three hydrogen atoms--to the building block's precursor molecule called deoxy-uridine monophosphate, or dUMP. Even though both reactions accomplish this key step, the reaction mechanisms, or steps, catalyzed by the FDTS and TS enzymes are structurally different.

A potential therapeutic target for gastric cancer

Gastric cancer (GC) is the fourth most common malignancy and the second most frequent cause of cancer-related death in the world. The carcinogenesis of GC involved numerous genetic and epigenetic alterations, as well as many environmental risk factors. Environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs) and halogenated hydrocarbons (HAHs) are well-known carcinogens that play important roles in GC development. The toxic effects of PAHs and HAHs are mediated by a conserved signaling pathway that binds and activates the aryl hydrocarbon receptor (AhR). AhR is a ligand-activated transcription factor and can mediate the carcinogenic and other toxic effects of a variety of environmental pollutants. Many studies in recent years have demonstrated a close relationship between AhR and tumorigenesis. However, the role of AhR in gastric tumorigenesis is still unclear. A research team led by Dr Min-Hu Chen from China addressed this question. Their study will be published on April 14, 2009 in the World Journal of Gastroenterology.
In this study, RT-PCR, real-time PCR, and Western blotting were performed to detect AhR expression in 39 GC tissues and five GC cell lines. AhR protein was detected by immunohistochemistry (IHC) in 190 samples: 30 chronic superficial gastritis (CSG), 30 chronic atrophic gastritis (CAG), 30 intestinal metaplasia (IM), 30 atypical hyperplasia (AH), and 70 GC. The AhR agonist tetrachlorodibenzo-para-dioxin (TCDD) was used to treat AGS cells. MTT assay and flow cytometric analysis were performed to measure the viability, cell cycle and apoptosis of AGS cells. They found that AhR expression was significantly increased in GC tissues and GC cell lines. IHC results indicated that the levels of AhR expression gradually increased, with the lowest levels in CSG, followed by CAG, IM, AH and GC. AhR expression and nuclear translocation were significantly higher in GC than in precancerous tissues. TCDD inhibited proliferation of AGS cells via induction of growth arrest at the G1-S phase.

Alpha-fetoprotein can affect the development of rat colons?

Mammalian alpha-fetoprotein (AFP) is a single-chain glycoprotein and altered serum AFP levels have been observed concurrent with aberrant growth manifestations in some congenital defects and cancer. The gut development during late gestation and early neonatal period is accompanied by changes in the synthesis of AFP, and abundance declines significantly during gut development. In this case, AFP is considered as an important growth factor with a specific function in gastrointestinal development. The ontogeny of AFP gene expression has been examined in the fetal and adult mouse gastrointestinal tract to understand the basis of the ontogeny of AFP transcription in the gut and its regulatory elements. However, little is known about the expression pattern of AFP genes or its involvement during rat colon development.A research team led by Dr Ying-Bin Ge from Nanjing Medical University, China addressed this question. Their study will be published on April 14, 2009 in the World Journal of Gastroenterology. Colons from Sprague-Dawley rat fetuses, young and adult (8 wk old) animals were used in this study. Expression levels of AFP in colons of different development stage were detected by reverse transcriptase PCR (RT-PCR) and Western blotting. To identify the cell location of AFP in the developing rat colons, double-immunofluorescent staining was performed using antibodies to specific cell markers and AFP, respectively. They found that the highest levels of AFP mRNA were detected in colons of rats at embryonic day 18.5 (e18.5). Compared to e18.5 d, the AFP expression was significantly decreased during rat development [85% for e20.5, P < 0.05, 58% for postnatal day 0.5 (P0.5), P < 0.05, 37% for P7, P < 0.05, 24% for P14, P < 0.05, and 11% for P21, P < 0.05] and undetected in adult rats. Only the 72-kDa isoform of AFP was detected by Western blotting, the expression pattern was similar to AFP mRNA and conformed to the results of mRNA expression. The AFP positive staining was identical to different distribution patterns in fetuses, young and adult animals and positive staining for both AFP and vimentin was overlapped in mesenchymal cells at each stage tested.

Inexpensive drug appears to relieve fibromyalgia pain in Stanford pilot study

For Tara Campbell, the onset of her fibromyalgia began slowly with repeated sore throats, fevers and fatigue. By the time she was diagnosed, a year later, she had become so debilitated by flulike symptoms and exhaustion that she often couldn't get off the couch all day."Fall, a year ago, I hit my very, very worst," said Campbell, 39, of Walnut Creek, Calif. "I felt overall pain to the point that even when my children or husband just touched me it hurt." Campbell's symptoms still linger, but since taking part in a Stanford University School of Medicine clinical trial in the spring of 2008, she's improved enough that she's gone back to working again as an interior decorator and even headed up the fundraising auction at her daughters' school. "I am really, really good," Campbell said. "Having said that, I'm still not 100 percent. I'm still not that person I was before." Campbell was one of 10 women with fibromyalgia to take part in a small pilot study at Stanford over a 14-week period to test the new use of a low dose of a drug called naltrexone for the treatment of chronic pain. The drug, which has been used clinically for more than 30 years to treat opioid addiction, was found to reduce symptoms of pain and fatigue an average of 30 percent over placebo, according to the results of the study to be published April 17 online in the journal Pain Medicine. "Patients' reactions were really quite profound," said senior author Sean Mackey, MD, PhD, associate professor of anesthesia and chief of the pain management division at Stanford University Medical Center. "Some people decided to come off other medications. Some people went back to work really improving their quality of life." Still, Mackey and his colleagues remain cautious about recommending the drug this early on in the research process. "People need to understand that while we're excited about preliminary results, they are still preliminary, and we need to do longer studies with more patients. There is still a significant amount of work to be done." The researchers are moving ahead with a second, longer-term trial of 30 patients who will be tested during a 16-week period. The drug is particularly promising, the study states, because of the few treatment options available for fibromyalgia patients, its low cost of about $40 a month and its limited side effects. Vivid dreams were reported by a few participants. Still considered a controversial diagnosis, fibromyalgia is a disorder classified by chronic widespread pain, debilitating fatigue, sleep disturbance and joint disorder. Advocates and doctors who treat the disorder, estimate it affects as much as 4 percent of the population. "The symptoms of fibromyalgia are commonly seen in a number of other diseases, and there is no well-established and objective blood test to confirm the diagnosis," said Jarred Younger, PhD, the study's lead author and an instructor in anesthesia and pain management at Stanford. "In the meantime, new treatments that work particularly well for fibromyalgia go a long way toward validating the usefulness of the diagnosis."

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